Proportion Of Symptomatic Patients Research Articles

Carotid Endarterectomy and Carotid Artery Stenting in the US Medicare Population, 1999-2014

Carotid endarterectomy and carotid artery stenting are the leading approaches to revascularization for carotid stenosis, yet contemporary data on trends in rates and outcomes are limited. To describe US national trends in performance and outcomes of carotid endarterectomy and stenting among Medicare beneficiaries from 1999 to 2014. Serial cross-sectional analysis of Medicare fee-for-service beneficiaries aged 65 years or older from 1999 to 2014 using the Medicare Inpatient and Denominator files. Spatial mixed models adjusted for age, sex, and race were fit to calculate county-specific risk-standardized revascularization rates. Mixed models were fit to assess trends in outcomes after adjustment for demographics, comorbidities, and symptomatic status. Carotid endarterectomy and carotid artery stenting. Revascularization rates per 100 000 beneficiary-years of fee-for-service enrollment, in-hospital mortality, 30-day stroke or death, 30-day stroke, myocardial infarction, or death, 30-day all-cause mortality, and 1-year stroke. During the study, 937 111 unique patients underwent carotid endarterectomy (mean age, 75.8 years; 43% women) and 231 077 underwent carotid artery stenting (mean age, 75.4 years; 49% women). There were 81 306 patients who underwent endarterectomy in 1999 and 36 325 in 2014; national rates per 100 000 beneficiary-years decreased from 298 in 1999-2000 to 128 in 2013-2014 (P < .001). The number of patients who underwent stenting ranged from 10 416 in 1999 to 22 865 in 2006 (an increase per 100 000 beneficiary-years from 40 in 1999-2000 to 75 in 2005-2006; P < .001); by 2014, there were 10 208 patients who underwent stenting and the rate decreased to 38 per 100 000 beneficiary-years (P < .001). Outcomes improved over time despite increases in vascular risk factors (eg, hypertension prevalence increased from 67% to 81% among patients who underwent endarterectomy and from 61% to 70% among patients who underwent stenting) and the proportion of symptomatic patients (all P < .001). There were adjusted annual decreases in 30-day ischemic stroke or death of 2.90% (95% CI, 2.63% to 3.18%) among patients who underwent endarterectomy and 1.13% (95% CI, 0.71% to 1.54%) among patients who underwent stenting; an absolute decrease from 1999 to 2014 was observed for endarterectomy (1.4%; 95% CI, 1.2% to 1.5%) but not stenting (-0.1%; 95% CI, -0.5% to 0.4%). Rates for 1-year ischemic stroke decreased after endarterectomy (absolute decrease, 3.5% [95% CI, 3.2% to 3.7%]; adjusted annual decrease, 2.17% [95% CI, 2.00% to 2.34%]) and stenting (absolute decrease, 1.6% [95% CI, 1.2% to 2.1%]; adjusted annual decrease, 1.86% [95% CI, 1.45%-2.26%]). Additional improvements were noted for in-hospital mortality, 30-day stroke, myocardial infarction, or death, and 30-day all-cause mortality as well as within demographic subgroups. Among fee-for-service Medicare beneficiaries, the performance of carotid endarterectomy declined from 1999 to 2014, whereas the performance of carotid artery stenting increased until 2006 and then declined from 2007 to 2014. Outcomes improved despite increases in vascular risk factors.

Accidental microembolic signals: prevalence and clinical relevance

The purpose of this study was to examine the occurrence of accidental microembolic signals (MES) and its clinical relevance in patients receiving routine transcranial Doppler (TCD) examinations. We retrospectively reviewed our institutional TCD database (from January 2007–November 2012). The arteries with positive MES, the presumed sources of emboli and the clinical backgrounds were analyzed. A total of 10,067 patients received routine TCD examinations in our laboratory during the research period. MES were detected in 98 arteries of 78 patients, with a frequency of 0.77 % of all the recruited patients. A high percentage of MES (64.3 %) were detected in MCAs. Sixty five (83.33 %) accidental emboli were from arterial sources, including atherosclerotic cerebral or carotid artery stenosis (n = 45), moyamoya disease (n = 11), intracranial arteries (n = 3) and Takayasu arteritis (n = 3). Thirteen (16.67 %) emboli were from cardiac sources, including atrial fibrillation (n = 3), artificial valves (n = 8), infective endocarditis (n = 2), patent foramen ovale (n = 2), and systemic lupus erythematosus (n = 1). In artificial valves disease, all patients with MES were asymptomatic, while in atherosclerotic cerebral or carotid artery stenosis, 66.67 % (n = 30) patients with MES were symptomatic. In different diseases with accidental MES, the proportion of symptomatic patients and asymptomatic patients were different (p < 0.001). MES are not uncommon during routine TCD examinations, the clinical value of which varied in different diseases.

The Impact of Carotid Artery Stenting on Cognitive Function in Patients with Extracranial Carotid Artery Stenosis

The effect of carotid artery stenting (CAS) on cognitive function in patients with extracranial carotid artery stenosis is equivocal. The aim of this study was to examine the impact of CAS on various domains of cognitive function. We performed a meta-analysis of the studies evaluating various domains of cognitive function before and after CAS, namely, (1) global cognition using Mini-Mental State Examination (MMSE) and Rey Auditory Verbal Learning Test (RAVLT), (2) executive function using Trail Making Test (TMT) A or Color Trails Test (CTT) A and TMT B or CTT B, (3) language ability using Boston Naming Test (BNT), (4) memory, (5) attention/psychomotor speed, and (6) functional ability, using various cognitive tests. Pooled weighted mean differences (WMDs) and standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were appropriately calculated using fixed or random effects models after assessing between-study heterogeneity. Meta-regression analysis was performed with number of patients per study; mean age (years); follow-up (months); proportion of men; proportion of patients with hypertension, diabetes mellitus, hyperlipidemia, smoking, and coronary artery disease; proportion of symptomatic patients; and degree of ipsilateral and degree of contralateral carotid stenosis as covariates. Sixteen studies were eligible, including a total of 626 CAS patients. A statistically significant improvement of global cognition was detected with MMSE (WMD = 0.67, 95% CI = 0.29-1.05, P < 0.001; follow-up = 5.6 months), but not with RAVLT (SMD = 0.45, 95% CI = -0.03 to 0.93, P = 0.07; follow-up = 2.4 months). Significant improvement of memory (SMD = 0.33, 95% CI = 0.11-0.55, P < 0.01; follow-up = 4.1 months) and attention/psychomotor speed (SMD = 0.21, 95% CI = 0.04-0.39, P = 0.02; follow-up = 4 months) was also detected. No statistically significant effect on executive function (TMT A/CTT A and TMT B/CTT B; SMD = 0.08, 95% CI = -0.10 to 0.26, P = 0.39; follow-up = 3.9 months and SMD = -0.02, 95% CI = -0.20 to 0.16, P = 0.82, respectively; follow-up = 3.9 months), language ability (BNT; SMD = 0.24, 95% CI = -0.05 to 0.54, P = 0.10; follow-up = 4 months), and functional ability (SMD = -0.05, 95% CI = -0.25 to 0.15, P = 0.63; follow-up = 3.8 months) was observed. No significant effects of the examined covariates were demonstrated in the meta-regression analyses. CAS may be associated with improvement in global cognition, memory, and attention/psychomotor speed. There was no positive effect on executive function, language, and functional ability, but CAS was not associated with a decline in any area of cognitive function. Future studies in larger groups of patients are probably needed to fully investigate the long-term effect of CAS on cognition in patients with carotid artery stenosis.

Is colorectal biopsy necessary in irritable bowel syndrome?

Background Clinical symptom based criteria for IBS is not sufficient enough to rule out microscopic colitis (MC). We sought to study whether biopsy is necessary in IBS. Methods This prospective study included colonic mucosa of 197 patients with IBS (129 IBS-D, 50IBS-C and 18 IBS-M) to rule out MC. Results Overall prevalence of MC in patients with IBS was 23.4% (46/197). The prevalence of MC in patients with IBS-D was 28.7% (37/129), higher than in patients with IBS-C 12% (6/50) and IBS-M 16.7% (3/18). Conclusions Microscopic colitis is present in a relevant proportion of symptomatic patients meeting diagnostic criteria for IBS. Despite the fact that IBS is a functional disorder, in many patients morphological changes occur in colon mucosa. The diagnostic criteria of IBS are not specific enough to exclude the presence of MC. Therefore, in patients of IBS, it may be reasonable to perform a biopsy to screen for MC.

Profile and clinical features of HIV positive patients attending Integrated Counseling and Testing Centre in a Medical College Hospital of Hassan, Karnataka

Background: HIV infection is a major public health problem as it has dramatically increased the global burden of disease. HIV infected patients experience a variety of clinical signs and symptoms. Objective: Our objective was to study the profile of clinical features and opportunistic infections in HIV infected patients attending a tertiary care medical college hospital in Hassan, Karnataka. Materials and Methods: A total of 124 HIV infected patients attending the ART Centre and the ICTC of Hassan Institute of Medical Sciences, Hassan, Karnataka were enrolled in the study, after obtaining informed consent. Clinical symptoms were recorded by direct questioning. Documented opportunistic infections were noted from patient records. Results: 80 (64.5%) HIV positive patients were males and 44 (35.5%) females. Mean age of the patients was 36.5 ± 6.0 years. The common symptoms were lethargy and fatigue 90 (72.5%), prolonged fever 86 (69.3%), weakness 84 (67.7%), body-ache and joint pain 84 (67.7%), loss of appetite 82 (66.1%), weight loss 80 (64.5%), cough (44.5%), chronic diarrhoea 68 (54.8%) and Nausea and Vomiting 64 (51.6%).The overall proportion of symptomatic patients was significantly higher than the number with etiologically documented opportunistic infections (41.9%). Pulmonary tuberculosis (37.9%) was the most frequently documented opportunistic infection. Conclusion: Affordable high quality laboratory diagnostic facilities for the diagnosis of opportunistic infections under the public health program will help to obtain an accurate picture of the range of opportunistic infections in HIV patients in India.

P2-15-02: Are We Performing More Mastectomies on Women Diagnosed with Invasive Breast Cancer?

Abstract Introduction: Surgical management of breast cancer has changed over the past several decades; breast-conserving surgery has become widely accepted. Mastectomies, however, are still being performed as part of the management of breast cancer. The aim of this study was to investigate the indications for mastectomy in women with invasive breast cancer within our institution. Method: A systematic review of all new patients with invasive breast cancer treated with surgical intervention at our breast unit in the years 2000, 2005 and 2009 was performed. Using our databases, patient demographics, tumour characteristics and reasons for mastectomy were examined. Screen-detected and symptomatic patients were included in the study. Patients excluded were those with incomplete data and recurrent breast cancer. Results: A total of 584 patients (F:M, 576:8); with cancer types which included invasive ductal carcinoma (n=501, 84%), invasive lobular carcinoma (n=51, 9%), invasive tubular carcinoma (n=27, 5%) and sarcomas (n=5, 1%) were studied. Conclusion: In our institution, the majority of patients with screen-detected invasive breast cancer fulfilled the criteria to have breast-conserving surgery; mastectomy rate for screen-detected cancers remained stable. However, we found that in the symptomatic patient group, there was an increase in mastectomy rate from 16% (n=170) in 2000 to 52% (n=225) in 2009. Despite this trend, our results were still in keeping with the national standard as illustrated by the National Cancer Intelligence Network, where they noted that in 2006, 52% of symptomatic patients with invasive breast cancer underwent mastectomy in the United Kingdom. The reason for a higher mastectomy rate in symptomatic patients compared to screen-detected patients in 2009 is multifactorial. We found that a larger proportion of symptomatic patients presented with larger tumours and tumours which were multifocal in nature. Other factors which may have contributed included more accurate estimation of tumour size by imaging (e.g. MRI) and patient choice. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-02.

Combined anterior vaginal wall mesh with sacrospinous ligament fixation or with posterior intravaginal slingplasty for uterovaginal or vaginal vault prolapse

ObjectiveTo evaluate outcomes of anterior vaginal wall mesh augmentation with concomitant sacrospinous ligament fixation (SSLF) or with concomitant posterior intravaginal slingplasty (IVS) for uterovaginal or vaginal vault prolapse. Study designWomen with symptomatic uterovaginal or vaginal vault prolapse were randomly allocated to SSLF or IVS. All underwent concomitant anterior repair augmented with self-tailored multifilament polypropylene and polyglactin composite mesh. Before and 2, 12, 24 and 36 months after surgery, the outcome was assessed by examination and standard questions. The primary endpoint was anatomic recurrence of pelvic organ prolapse at stage II or beyond (−1cm or greater) at any site of the vaginal wall. Secondary outcomes included perioperative and postoperative complications, symptom resolution, reoperation and mesh exposure. ResultsTwenty-two women were recruited from March 2003 to December 2005. At 3-year follow-up3 (2 posterior and 1 apical) out of 14 (21%) in the IVS group had anatomic recurrences of pelvic organ prolapse, and 1 anterior out of 8 (13%) in the SSLF group. Severe operative complications or reoperations did not occur. The proportions of symptomatic patients, including those with dyspareunia, did not differ between the groups. Erosion of the anterior multifilament mesh was found in 2 out of 22 cases (9%; 95% CI 3–28%). ConclusionAt 3-year follow-up anterior repair reinforced with a composite mesh with concomitant sacrospinous ligament fixation or with concomitant posterior intravaginal slingplasty allowed feasible support in patients with severe pelvic organ prolapse.

Outcomes after anterior vaginal wall repair with mesh: a randomized, controlled trial with a 3 year follow-up

The objective of the study was to compare anterior colporrhaphy with and without a mesh. Two hundred two women with anterior prolapse were assigned to undergo colporrhaphy alone or reinforced with a tailored polypropylene mesh. Before and 2, 12, 24, and 36 months after surgery, the outcome was assessed by examination and standard questions. The primary endpoint was anatomic recurrence of anterior vaginal prolapse. Secondary outcomes were symptom resolution, reoperation, and mesh exposure. Recurrences of anterior vaginal prolapse were noted in 40 of the 97 (41%) in the colporrhaphy group and 14 of 105 (13%) in the mesh group (P < .0001). The number needed to treat was thus 4. The proportion of symptomatic patients, including those with dyspareunia, did not differ between the groups. The mesh erosion rate was 19%. At 3 year follow-up, anterior colporrhaphy with mesh reinforcement significantly reduced anatomic recurrences of anterior vaginal prolapse, but no difference in symptomatic recurrence were noted and the mesh erosion rate was high. The use of mesh was not associated with an increase in dyspareunia.

Ist Diabetes mellitus ein eigenständiger Risikofaktor in der Karotischirurgie?

BackgroundThe status of diabetes mellitus as a predictor of poor outcome after carotid endarterectomy (CEA) is controversial. The objective of this study was to evaluate and compare the perioperative death and stroke rates after CEA in patients with and without diabetes.Material and methodsA retrospective analysis of 1,291 patients (mean age 68.6 years, SD 8.9 years; 920 men) undergoing CEA for carotid artery stenosis between January 1999 and January 2005 was performed.ResultsOf this study population, 28.4% (n=366) were diabetic. The same proportion of symptomatic patients was seen in both groups (48% diabetics vs. 43% nondiabetics; not significant). No differences regarding surgical technique, degree of stenosis, operating time, or clamping time were observed. Selective shunting was used significantly more often in diabetics (32%) than in nondiabetics (24%; p=0.002, odds ratio 1.535, 95% confidence interval 1.177–2.001). The perioperative stroke rate in diabetic patients was 3.8% (n=14/366) compared to 2.8% (25/925) in nondiabetic patients (p=0.343). The overall mortality was 0.54% (n=7/1,291); 0.27% (n=1) in diabetics and 0.62% (n=6) in nondiabetics (p=0.408). The combined death and stroke rate was 3.4% in diabetics versus 4.1% in nondiabetics (p=0.584).ConclusionIn this study, the presence of diabetes did not influence perioperative stroke and death rates after CEA. Shunt insertion was significantly more frequent in diabetic patients.

Cavernous malformations at the crossroads

Our understanding of cavernous malformations (CMs) of the brain and spinal cord continues to improve. 1 Nevertheless, there are still several points in this intriguing story needing further elucidation. The rapid evolution of knowledge about the molecular pathogenesis of CMs has culminated in the recent finding of a potential fourth cerebral CM locus. 4 Differences between familial and sporadic forms continue to be recognized. The proportion of symptomatic patients with familial CMs who suffer cerebral hemorrhage is higher than that reported in patients with sporadic CMs. Hemorrhage tends to occur at a younger age in familial than in sporadic CMs, 4 probably due to “anticipation” in the inherited disease. A recent demonstration of ultrastructural differences between hemorrhagic and nonhemorrhagic malformations deepens our understanding of the mechanisms underlying the more aggressive behavior of some CMs. 6 Most of the research converges on the genetic aspects of the disease (see the articles by Mindea, et al., and Dashti, et al., in this issue). 3 Many doubts still surround the sporadic form: is it due to a genetic factor, an environmental trigger, or both? If sporadic lesions are usually solitary, what is the significance of multiple lesions in apparently sporadic cases? How many “solitary” CMs are really familial? Although in familial CMs the formation of new lesions is well codified (with continuous formation throughout the decades of a patient’s life and also after the age of 50 years), what is the impact of de novo lesions in the cauldron of sporadic CMs? In this regard, the problem of environmental triggers (irradiation, hormones, infection) is particularly important and still unresolved. Almost all CMs that arise after irradiation occur in infancy (see the review article by Nimjee, et al., in this issue) and many are multiple, as though the infant brain were more sensitive to radiation. Hormonal effects, particularly in pregnancy, are often claimed in hemorrhagic CMs, but the key mechanism igniting bleeding and growth is obscure: the responsibility of maternal growth factors, both local and systemic, and of estrogenic endothelial proliferation should be more deeply investigated (see the case report by Safavi-Abbasi, et al., in this issue). Viral infection, inflammation, and immune responses might play an important albeit obscure role. Further understanding of the potential role of these factors may open unanticipated ways to modulate CMs therapeutically. It is generally believed that familial and sporadic CMs have identical pathological characteristics, but developmental venous anomalies (DVAs), with their hemodynamic burden, are associated only with the sporadic form and are practically absent in the familial form. The familial form is a “pure” pathological lesion, whereas the sporadic form is often a “hybrid” one, with venous and capillary malformations associated with the CM. The case report by Lekovic and coworkers once again stresses the mutual relationships between CMs and associated DVAs and the potential role of the DVA in growth and rupture of the coexistent CM (see also the review by Perrini and Lanzino in this issue). The recurrence of CMs associated with DVAs suggests a causal relationship between the two. 5 Further elucidation of the pathogenesis and clinical behavior of CMs can be gained by understanding the role of the associated DVA. The ultrastructural study of genetic and pathological interactions is promising, 2 and a wider use of electron microscopy is recommended for a better understanding of the pathophysiological features of CMs. Magnetic resonance (MR) imaging has been extremely useful, not only in terms of the diagnosis of CMs but also in predicting the prognosis, with the classification of CMs in four different types based on MR imaging characteristics. 7 In this regard, better clinical/neuroimaging correlations should be implemented to gain a better understanding of inactive or dormant lesions. This understanding may modify our therapeutic stance. Unfortunately, “neuroradiological penetrance” is incomplete and some patients with the KRIT1 mutation have normal results on MR imaging. In this respect, does a CM that is “occult” on MR imaging exist? It is possible that, besides the Type 4 CM (with its problems of interpretation), “immature,” “transient,” “precursor,” and “early” aspects of the disease still escape MR imaging detection. As our understanding improves, we need better convergence and interaction of the genetic, pathological, clinical, and neuroimaging aspects to achieve complete comprehension of this protean disease.

Clinical and Biochemical Characteristics and Genotype-Phenotype Correlation in 143 Finnish and Russian Patients With Acute Intermittent Porphyria

Acute intermittent porphyria (AIP), resulting from a deficiency of porphobilinogen deaminase (PBGD) in heme biosynthesis, is genetically heterogeneous and manifests with variable penetrance. The clinical outcome, prognosis, and correlation between PBGD genotype and phenotype were investigated in 143 Finnish and Russian AIP patients with 10 mutations (33G-->T, 97delA, InsAlu333, R149X, R167W, R173W, R173Q, R225G, R225X, 1073delA). Thirty-eight percent of the patients had experienced 1 or more acute attacks during their lives. The proportion of symptomatic patients has decreased dramatically from 49% to 17% among patients diagnosed before and after 1980, respectively. Patients with the R167W and R225G mutations showed lower penetrance (19% and 11%, respectively) and recurrence rate (33% and 0%, respectively) than patients with other mutations (range, 36%-67% and 0%-66%, respectively). Moreover, urinary excretions of porphyrins and their precursors were significantly lower in these patients (porphobilinogen [PBG], 47 +/- 10 vs. 163 +/- 21 micromol/L, p < 0.001; uroporphyrin, 130 +/- 40 vs. 942 +/- 183 nmol/d, p < 0.001). Erythrocyte PBGD activity did not correlate with PBG excretion in remission or with the clinical severity of the disease. Mutations R167W and R225G resulted in milder biochemical abnormalities and clinical symptoms indicating a milder form of AIP in these patients. In all AIP patients, normal PBG excretion predicted freedom from acute attacks. The risk of symptoms was highest for female patients with markedly increased PBG excretion (>100 micromol/L). Proper counseling contributed to the prevention of subsequent attacks in 60% of previously symptomatic and in 95% of previously symptom-free patients.

Epidemiological, clinical and histopathologic characteristics of celiac disease: Results of a case-finding population-based program in an Italian community

Objective. Celiac disease (CD) is underdiagnosed mainly because of lack of awareness of its heterogeneous clinical presentation. The Center for Surveillance and Control of Celiac Disease (CCD) was set up in June 2000 in the province of Brescia, Northern Italy (1,016,426) inhabitants to enhance case-finding, to standardize diagnostic criteria and to collect epidemiological data. Material and methods. The CCD has prompted an educational “celiac awareness program” in the primary-care setting focusing on selective serological screening of high-risk groups, and has reviewed by standardized criteria all diagnoses made in the province since 1984. Results. A total of 1437 CD patients have been identified by the CCD, 508 of them diagnosed after June 2000 during the 3 years of activity of the Center (M:F 2:1). Annual incidence was 0.11/1000 before and increased to 0.17/1000 during CCD activity, and this increase was greater for adult (from 0.07/1000 to 0.12/1000) than for pediatric CD (from 0.04/1000 to 0.05/1000). Mean age at diagnosis also increased from 20.2±17.7 years to 27.2±19.3 years (p<0.0001) as did the proportion of asymptomatic patients (8% versus 15%) before and during CCD activity. There was a linear trend towards increasing proportions of symptomatic patients with increasing severity of histopathologic lesions (p<0.03). Conclusions. Our results indicate that educational programs promoting serological screening of CD in high-risk groups are effective for case-finding in large communities, particularly among the adult population, and suggest that primary-care doctors caring for adults should be particularly targeted by “celiac awareness programs”.

The cost-effectiveness of syndromic management in pharmacies in Lima, Peru.

Many people with sexually transmitted diseases (STDs) in Lima, Peru, seek treatment in pharmacies. The goal was to assess the cost-effectiveness of training pharmacy workers in syndromic management of STDs. Cost-effectiveness from both the program and societal perspectives was determined on the basis of study costs, societal costs (cost of medicine), and the number of cases adequately managed. The latter was calculated from estimated incidence, proportion of symptomatic patients, proportion seeking treatment in pharmacies, and proportion of cases adequately managed in both comparison and intervention districts. Univariate and multivariate sensitivity analyses were performed. Under base-case assumptions, from the societal perspective the intervention saved an estimated US$1.51 per case adequately managed; from the program perspective, it cost an estimated US$3.67 per case adequately managed. In the sensitivity analyses, the proportion of females with vaginal discharge or pelvic inflammatory disease who seek treatment in pharmacies had the greatest impact on the estimated cost-effectiveness, along with the medication costs under the societal perspective. Training pharmacists in syndromic management of STDs appears to be cost-effective when only program costs are used and cost-saving from the societal perspective. Our methods provide a template for assessing the cost-effectiveness of managing STD syndromes, on the basis of indirect estimates of effectiveness.

Review of gemcitabine in biliary tract carcinoma

Cancers of the biliary tract are rare, and remain a major challenge to surgical, medical, and radiation oncologists. Unfortunately, the large majority of these tumors are not resectable at the time of initial diagnosis, and patients with advanced disease face a dismal prognosis. The efficacy of conventional palliative systemic chemotherapy (eg, with 5-fluorouracil, mitomycin-C, and cisplatin) seems negligible, and there is presently no agreement on the best chemotherapeutic regimen. Gemcitabine is among several different new anticancer drugs under investigation in the treatment of advanced biliary tract cancer. Apart from its favorable toxicity profile, this novel nucleoside analog has shown activity in many solid tumors, including pancreatic adenocarcinoma. In view of the histogenetic affinity between the pancreas and the biliary tract, and several case reports describing the efficacy of gemcitabine in advanced gallbladder or cholangiocellular carcinoma, a number of phase II investigations have been undertaken. In the majority of these trials a conventional gemcitabine dose regimen of 1,000 to 1,200 mg/m 2 given over 30 minutes on 3 consecutive weeks followed by a week of rest has been used. In a total of seven studies involving 167 assessable patients, objective response rates up to 60% (36% in the largest trial composed of 39 evaluable patients), abrogation of progressive disease (complete response + partial response + stable disease) in 50% to 93%, and overall survival times ranging from 6.3 to 16 months, have been reported. The consensus is that the tolerance of treatment was remarkable with only exceptional patients (≤5%) experiencing grade 4 hematologic toxicities. Nonhematologic side effects were infrequent and almost exclusively mild to moderate. In three of the trials, a formal clinical benefit analysis was included, suggesting that a considerable proportion of symptomatic patients will experience relief of tumor-related symptoms and/or weight gain. Possible options currently being investigated to further improve the therapeutic results of gemcitabine monotherapy include modifications of the dose regimen as well as combinations with other potentially synergistic anticancer drugs. In the latter approach, preliminary data have been reported for gemcitabine plus cisplatin, oxaliplatin, docetaxel, mitomycin-C, and continuous-infusion 5-fluorouracil/leucovorin. Objective response rates as high as 53% (for gemcitabine/cisplatin), and median survival times ≥11 months with only a slight increase in frequency and severity of side effects have been reported. In conclusion, while the best available chemotherapeutic treatment for advanced biliary tract cancer remains to be determined, accumulating data from recent phase II trials suggest that single-agent gemcitabine represents an active and very well-tolerated treatment option. It may also be safely combined with other drugs, though further improvements in response activity and survival warrant confirmation in future randomized studies. Semin Oncol 29 (suppl 20):40-45. Copyright 2002, Elsevier Science (USA). All rights reserved.

Review of gemcitabine in biliary tract carcinoma.

Cancers of the biliary tract are rare, and remain a major challenge to surgical, medical, and radiation oncologists. Unfortunately, the large majority of these tumors are not resectable at the time of initial diagnosis, and patients with advanced disease face a dismal prognosis. The efficacy of conventional palliative systemic chemotherapy (eg, with 5-fluorouracil, mitomycin-C, and cisplatin) seems negligible, and there is presently no agreement on the best chemotherapeutic regimen. Gemcitabine is among several different new anticancer drugs under investigation in the treatment of advanced biliary tract cancer. Apart from its favorable toxicity profile, this novel nucleoside analog has shown activity in many solid tumors, including pancreatic adenocarcinoma. In view of the histogenetic affinity between the pancreas and the biliary tract, and several case reports describing the efficacy of gemcitabine in advanced gallbladder or cholangiocellular carcinoma, a number of phase II investigations have been undertaken. In the majority of these trials a conventional gemcitabine dose regimen of 1,000 to 1,200 mg/m(2) given over 30 minutes on 3 consecutive weeks followed by a week of rest has been used. In a total of seven studies involving 167 assessable patients, objective response rates up to 60% (36% in the largest trial composed of 39 evaluable patients), abrogation of progressive disease (complete response + partial response + stable disease) in 50% to 93%, and overall survival times ranging from 6.3 to 16 months, have been reported. The consensus is that the tolerance of treatment was remarkable with only exceptional patients (< or = 5%) experiencing grade 4 hematologic toxicities. Nonhematologic side effects were infrequent and almost exclusively mild to moderate. In three of the trials, a formal clinical benefit analysis was included, suggesting that a considerable proportion of symptomatic patients will experience relief of tumor-related symptoms and/or weight gain. Possible options currently being investigated to further improve the therapeutic results of gemcitabine monotherapy include modifications of the dose regimen as well as combinations with other potentially synergistic anticancer drugs. In the latter approach, preliminary data have been reported for gemcitabine plus cisplatin, oxaliplatin, docetaxel, mitomycin-C, and continuous-infusion 5-fluorouracil/leucovorin. Objective response rates as high as 53% (for gemcitabine/cisplatin), and median survival times > or = 11 months with only a slight increase in frequency and severity of side effects have been reported. In conclusion, while the best available chemotherapeutic treatment for advanced biliary tract cancer remains to be determined, accumulating data from recent phase II trials suggest that single-agent gemcitabine represents an active and very well-tolerated treatment option. It may also be safely combined with other drugs, though further improvements in response activity and survival warrant confirmation in future randomized studies.

Quantification of the heart rate-independent vasodepressor component in carotid sinus syndrome.

In 45 patients with carotid sinus syndrome, the heart rate-independent vasodepressor component under ventricular and av-sequential pacing of the heart was investigated both in supine and in standing patients. Under both forms of pacing, the carotid pressure determination has led to a marked lowering of systolic and diastolic arterial blood pressure which is significantly more pronounced under orthostasis. The blood pressure values reached both in supine and in standing patients are significantly higher under av-sequential pacing than under ventricular pacing. Accordingly, the proportion of symptomatic patients is less under av-sequential pacing in the supine position (17% versus 29%) and in standing (65% versus 83%). The heart rate-independent vasodepressor reaction is maximal on average between 11 s and 16 s after the beginning of the carotid pressure test and persists for 3 s to 7 s. The blood pressure reaches initial values again after 14 s to 20 s. To summarize, these data document that a clinically relevant heart rate-independent vasodepressor reaction is to be reckoned with in the majority of patients with carotid sinus syndrome. This shows a different time course than the vagally determined effect of the carotid sinus reflex on heart rate. Orthostasis intensifies the vasodepressor reaction so that the hemodynamically more favorable av-sequential pacing which is actually more favorable in hemodynamic terms cannot guarantee freedom from symptoms in the majority of patients in the upright standing position.