The Use of Oral Anticoagulation Is Not Independently Associated with Mortality in Frail Older Patients with Repeated Falls.

BACKGROUND: Particularly in frail patients, anticoagulation may be underused because of the fear of bleeding. OBJECTIVE: To determine whether the use of antithrombotic medication is an independent risk factor for mortality in frail elderly with repeated falls. METHODS: All patients aged 65 years or older at the Fall and Syncope Clinic were eligible. Frailty was calculated with a Frailty Index (FI) based on the accumulation of deficits model. Risks were calculated with a cox regression analysis, adjusted for age, sex, and Frailty Index. RESULTS: 663 patients were included in this analysis. The median age was 80 years, 438 were women (66%), 73% had polypharmacy, and 380 patients (57%) had cognitive impairment. The mean FI was 0.23 (sd 0.09), 182 patients were moderately frail (27.5%), and 259 (39.1%) were severely frail. A total of 140 (21%) used oral anticoagulation and 223 (34%) used antiplatelet agents. A total of 196 patients (29.6%) died during follow-up. In the adjusted cox regression model, the use of neither antiplatelets nor anticoagulation was associated with mortality. A strong association was found with frailty (HR 74.0, 95% CI 13.1-417.3) and a weak association with age (HR 1.05, 95% CI 1.03-1.08). A lower risk of mortality was seen in women (HR 0.5, 95% CI 0.3-0.6). CONCLUSIONS: In this cohort of frail older patients, there was no independent association between the use of antithrombotic medication and mortality. A strong association with mortality was found with frailty, a weak association was found with age, and a lower mortality risk was found in women. Our data indicate that the fear of bleeding or increased mortality in frail patients with an indication for oral anticoagulation may be unjustified.

Atrial fibrillation in cancer: thromboembolism and bleeding in daily practice.

Background: Cancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF). Objectives: We aimed to describe current anticoagulant practice in patients with AF and active cancer, present incidences of thromboembolic and bleeding complications, and evaluate the association between cancer type or anticoagulant management strategy with AF-related complications. Methods: This retrospective study identified patients with AF and active cancer in 2 hospitals between January 1, 2012, and December 31, 2017. Follow-up lasted for 2 years. Data on cancer and anticoagulant treatment were collected. The outcomes of interest included ischemic stroke or transient ischemic attack (TIA) and clinically relevant nonmajor bleeding (CRNMB/MB). Incidence rates (IRs) per 100 patient-years and subdistribution hazard ratios (SHRs) with corresponding 95% Cis were estimated. Results: We identified 878 patients with AF who developed cancer (cohort 1) and 335 patients with cancer who developed AF (cohort 2). IRs for ischemic stroke/TIA and MB/CRNMB were 3.9 (2.8-5.3) and 15.7 (13.3-18.5) for cohort 1 and 4.0 (2.2-6.7) and 16.7 (12.6-21.7) for cohort 2. 14.2% (cohort 1) and 19.1% (cohort 2) of patients with a CHA2DS2-VASc score of ≥2 did not receive anticoagulant treatment. Withholding anticoagulants was associated with thromboembolic complications (SHR: 5.1 [3.20-8.0]). In nonanticoagulated patients with a CHA2DS2-VASc score of <2, IRs for stroke/TIA were 4.5 (0.75-15.0; cohort 1) and 16.0 (5.1-38.7; cohort 2). Conclusion: Patients with AF and active cancer experience high rates of thromboembolic and bleeding complications, underlying the complexity of anticoagulant management in these patients. Our data suggest that the presence of cancer is an important factor in determining the indication for anticoagulants in patients with a low CHA2DS2-VASc score.

[Anticoagulation useful in short episodes of atrial fibrillation?] / Antistolling zinvol bij kortdurend atriumfibrilleren?

In patients with short episodes of clinical, non-triggered AF is the evidence for long-term anticoagulation based on the CHA2DS2-VASc score strong. In situations where a temporary trigger for AF is observed (e.g. after surgery or an infection), or when AF is only detected on a cardiac implantable electronic device (CIED) or smartwatch, the evidence for anticoagulation is less well established. Despite the short duration of the AF episode(s), both patients with subclinical or triggered AF are often at an inherently increased risk of stroke or thromboembolism. In some of these cases long-term anticoagulation can be considered, especially when other cardiovascular risk factors are present. Important considerations when deciding to start with long-term anticoagulation are the individually estimated risk of thrombosis and bleeding, the implementation of shared decision making, and the optimization of the overall cardiovascular risk management.

Health economic evaluation of nation-wide screening programmes for atrial fibrillation in the Netherlands.

AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guidelines to prevent strokes. Cost-effectiveness analyses of different screening programmes for AF are difficult to compare because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programmes in the Netherlands. METHODS AND RESULTS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY, and ROCKET AF trials combined with Dutch observational data. Univariate, probabilistic sensitivity, and various scenario analyses were performed. The maximum number of newly detected AF patients in the Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of >3000 strokes prevented using single-time point AF screening. Compared with no screening, screening 100 000 people provided a gain in QALYs ranging from 984 to 8727 and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. The probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥75 years visiting the geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥65 years visiting the GPs office had the highest impact on strokes prevented. CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.

Preoperative cardiac screening using NT-proBNP in obese patients 50 years and older undergoing bariatric surgery: a study of 310 consecutive patients.

BACKGROUND: Obesity is associated with cardiovascular (CV) risk factors and diseases. Because bariatric surgery is increasingly performed in relatively elderly patients, a risk for pre- and postoperative CV complications exists. OBJECTIVES: We aimed to assess the value of plasma N-terminal-probrain natriuretic peptide (NT-proBNP) as a CV screening tool. SETTING: High-volume bariatric center. METHODS: Between June 2019 and January 2020, all consecutive bariatric patients 50 years and older underwent preoperative NT-proBNP assessment in this cohort study to screen for CV disease. Patients with elevated NT-proBNP (≥125 pg/mL) were referred for further cardiac evaluation, including electrocardiography and echocardiography. RESULTS: We included 310 consecutive patients (median age, 56 years; 79% female; body mass index = 43±6.5 kg/m2). A history of CV disease was present in 21% of patients, mainly atrial fibrillation (7%) and coronary artery disease (10%). A total of 72 patients (23%) had elevated NT-proBNP levels, and 67 of them underwent further cardiac workup. Of these 67 patients, electrocardiography (ECG) showed atrial fibrillation in 7 patients (10%). On echocardiography, 3 patients had left ventricular ejection fraction (LVEF) <40%, 9 patients had LVEF 40%-49%, and 13 patients had LVEF ≥50% with structural and/or functional remodeling. In 2 patients, elevated NT-proBNP prompted workup leading to a diagnosis of coronary artery disease and consequent percutaneous coronary intervention in 1 patient. CONCLUSIONS: Elevated NT-proBNP levels are present in 23% of patients 50 years and older undergoing bariatric surgery. In 37% of them, there was echocardiographic evidence for structural and/or functional remodeling. Further studies are needed to assess if these preliminary results warrant routine application of NT-proBNP to identify patients at risk for CV complications after bariatric surgery.

Quality of life after catheter and minimally invasive surgical ablation of paroxysmal and early persistent atrial fibrillation: results from the SCALAF trial.

AIMS: In the SCALAF trial, catheter-based pulmonary vein isolation (PVI) was as effective in long-term prevention of atrial fibrillation (AF) as minimally invasive thoracoscopic PVI and left atrial appendage ligation (MIPI). Catheter ablation (CA) resulted in significantly less major complications as compare to MIPI. We report quality of life (QOL) outcome in these patients. METHODS: In this study, 52 patients with symptomatic paroxysmal or early persistent AF were randomized to either MIPI or CA. QOL was assessed at baseline, 3, 6, and 12 months follow-up using the SF-36 Health Survey Questionnaire. AF-related symptoms were quantified at each follow-up visit using the European Heart Rhythm Association (EHRA) score. RESULTS: Median age was 57 years and 78% was male. Paroxysmal AF was present in 74%. At 3 months follow-up, physical role limitations (88.2 ± 29.5; versus 40.9 ± 44.0; P = 0.001, respectively) and bodily pain scores (95.5 ± 8.7; versus 76.0 ± 27.8; P = 0.021, respectively) were significantly higher after CA compared to MIPI, indicating less limitation in daily activity caused by physical problems and less pain after CA than after MIPI. AF symptoms assessed by the EHRA scores improved significantly at 3, 6, 12, and 24 months compared to baseline in both treatment groups (P < 0.001), with no significant differences between treatment groups. CONCLUSIONS: CA and MIPI ablation of AF both resulted in an improvement in several QOL measurements, although CA resulted in significantly less physical problems and bodily pain 3 months after treatment compared to MIPI. CLINICAL TRIAL NUMBER: ClinicalTrials.gov identifier: NCT00703157.

Atrial fibrillation and cancer - An unexplored field in cardiovascular oncology.

An increasing body of evidence suggests an association between cancer and atrial fibrillation (AF). The exact magnitude and underlying mechanism of this association are however unclear. Cancer-related inflammation, anti-cancer treatment and other cancer-related comorbidities are proposed to affect atrial remodelling, increasing the susceptibility of cancer patients for developing AF. Moreover, cancer is assumed to modify the risk of thromboembolisms and bleeding. A thorough and adequate understanding of these risks is however lacking, as current literature is scarce and show ambiguous results in AF patients. The standardized risk-models that normally aid the clinician in the decision of initiating anticoagulant therapy do not take the presence of malignancy into account. Other factors that complicate risk assessment in AF patients with cancer include drug-drug interactions and other cancer-related comorbidities such as renal impairment. In this review, we highlight the available literature regarding epidemiological association, risk assessment and anticoagulation therapy in AF patients with cancer.

Randomized Controlled Trial of Surgical Versus Catheter Ablation for Paroxysmal and Early Persistent Atrial Fibrillation.

BACKGROUND: Current guidelines recommend both percutaneous catheter ablation (CA) and surgical ablation in the treatment of atrial fibrillation, with different levels of evidence. No direct comparison has been made between minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation (surgical MIPI) versus percutaneous CA comprising of pulmonary vein isolation as primary treatment of atrial fibrillation. We, therefore, conducted a randomized controlled trial comparing the safety and efficacy of these 2 treatment modalities. METHODS: Eighty patients were enrolled in the study and underwent implantable loop recorder implantation. Twenty-eight patients did not reach randomization criteria. A total of 52 patients with symptomatic paroxysmal or early persistent atrial fibrillation were randomized, 26 to CA and 26 to surgical MIPI. The primary end point was defined as freedom of atrial tachyarrhythmias, without the use of antiarrhythmic drugs. The safety end point was freedom of complications. RESULTS: Median age was 57 years (range, 37-75), and 78% were men. Paroxysmal atrial fibrillation was present in 74%. Follow-up duration was ≥2 years in all patients. CA was noninferior to MIPI in terms of single-procedure arrhythmia-free survival after 2 years of follow-up (56.0% versus 29.2%; HR, 0.56; 95% CI, 0.26-1.20; log-rank P=0.059). Procedure-related major adverse events occurred significantly more often in MIPI than CA (20.8% versus 0%; P=0.029). CONCLUSIONS: Percutaneous pulmonary vein isolation was noninferior to MIPI in terms of efficacy and resulted in less complications. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00703157.

Ex vivo electrical impedance measurements on excised hepatic tissue from human patients with metastatic colorectal cancer.

Point-wise ex vivo electrical impedance spectroscopy measurements were conducted on excised hepatic tissue from human patients with metastatic colorectal cancer using a linear four-electrode impedance probe. This study of 132 measurements from 10 colorectal cancer patients, the largest to date, reports that the equivalent electrical conductivity for tumor tissue is significantly higher than normal tissue (p < 0.01), ranging from 2-5 times greater over the measured frequency range of 100 Hz-1 MHz. Difference in tissue electrical permittivity is also found to be statistically significant across most frequencies. Furthermore, the complex impedance is also reported for both normal and tumor tissue. Consistent with trends for tissue electrical conductivity, normal tissue has a significantly higher impedance than tumor tissue (p < 0.01), as well as a higher net capacitive phase shift (33° for normal liver tissue in contrast to 10° for tumor tissue).

Favorable long-term outcome of Maze surgery in patients with lone atrial fibrillation.

BACKGROUND: Rhythm control is indicated for patients suffering from symptomatic atrial fibrillation (AF), but remains difficult to establish. We investigated the long-term outcome of Cox maze III surgery in patients with symptomatic lone AF refractory to antiarrhythmic drug therapy. METHODS: Patients with a history of symptomatic paroxysmal or persistent AF refractory for at least two class I or III antiarrhythmic drugs and without structural heart disease or bradyarrhythmias were included. All patients underwent Cox maze III surgery. Complete success was defined as the absence of AF without antiarrhythmic drugs beyond 3 months after the procedure, and partial success as the absence of AF with antiarrhythmic drug use. RESULTS: A total of 29 patients were included (27 male), with a mean age of 48 +/- 6 years. At the time of surgery, 11 patients (38%) had persistent AF. After a mean follow-up of 4.8 +/- 2.4 years, 79% of patients had complete success, and 2 patients (7%) were free of AF with antiarrhythmic drugs. At the end of follow-up, left ventricular fractional shortening was significantly improved (from 31% +/- 10% to 39% +/- 8%, p = 0.002), left atrial size was unchanged, exercise capacity was within normal ranges, and quality of life was comparable with that of healthy controls. Severe complications included reoperations for postoperative bleeding (n = 3), pericardial effusion (n = 1), and mediastinitis (n = 1). In 2 patients, a pacemaker was implanted postoperatively because of sinus node dysfunction. CONCLUSIONS: Cox maze III surgery is a highly effective therapy for drug-refractory lone AF, and therefore remains an alternative to transvenous pulmonary vein ablation.

Variability of flow rate when collecting stimulated human parotid saliva.

The aim of this study was to estimate the accuracy and reproducibility of citric-acid-stimulated parotid saliva sampling. In healthy volunteers a strong correlation (r2 = 0.79) between flow rates from the left and right parotid gland was observed. In patients with Sjögren's syndrome this correlation (r2 = 0.90) was even stronger. The intraindividual variation in healthy volunteers was 23.3 +/- 5.9%. Increasing the number of collections did not reduce this variation significantly. In head and neck cancer patients, to estimate whether repeated measurements result in more reliable baseline values for use in clinical studies, repeated collections did not result in a significant reduction of intrapatient variation, similar to the results with the healthy volunteers. Thus, notwithstanding the good agreement between left and right flow rates, a high variation in parotid flow rates has to be considered when planning clinical trials evaluating the effects of treatment on salivary gland functioning.

Fluorodeoxyglucose positron emission tomography as an adjunct to carcinoembryonic antigen in the management of patients with presumed recurrent colorectal cancer and nondiagnostic radiologic workup.

BACKGROUND: The purpose of this study was to determine the role of fluorodeoxyglucose positron emission tomography (PET) in localizing disease in patients with colorectal cancer with radiologically occult symptomatology or increases in carcinoembryonic antigen (CEA) level. METHODS: Two hundred seventy-seven patients with colorectal cancer underwent PET scanning between November 1998 and September 2000 prompted by (1) increasing CEA level and nondiagnostic imaging or (2) symptoms with normal CEA level and nondiagnostic imaging. PET results were correlated with operative findings/histology, clinical follow-up data, and CEA level to determine PET's accuracy in determining the source of symptoms or CEA. RESULTS: Fifteen patients had increasing CEA levels, and 14 had abnormal PET. Two of these 14 were denied exploration because PET suggested widely metastatic disease. Nine patients underwent exploration with curative intent. In 1 patient, recurrence was not pathologically confirmed (false-positive rate, 8%). Two had disease beyond that predicted by PET, and 6 underwent complete resection and normalized their CEA levels. Four symptomatic patients with normal CEA levels and negative x-rays had abnormal PET; at exploration, 3 had no evidence of recurrence. CONCLUSIONS: PET imaging can often accurately localize the source of radiologically occult increases in CEA level and select that subset of patients eligible for therapeutic laparotomy. Symptomatic, PET-positive patients with normal CEA levels frequently undergo nontherapeutic laparotomy, and PET findings should be interpreted with caution in these patients.

Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is associated with microsatellite-unstable colorectal cancer development.

Hypermethylation of the MLH1 promoter underlies most sporadic colorectal cancers with microsatellite instability (MSI). To investigate the role of hypermethylation in the normal colonic mucosa as a possible precursor lesion, we studied 700 bp upstream of MLH1 covering 51 CpG sites. We found partially methylated alleles in 15 of 34 (44%) patients <60 years of age and 20 of 24 (83%) patients > or =80 years of age (P = 0.0026). Fully methylated alleles were present in 18 of 33 (55%) patients with MSI+ tumors but in only 18 of 90 (20%) patients with MSI- tumors (P = 0.00019). By in situ analysis, methylation was patchy and located mainly in the cryptal regions close to the lumen. We conclude that the spread of methylation in the MLH1 promoter in the normal colonic mucosa is closely associated with age and the development of sporadic MSI+ colorectal cancers.

18F-labeled fluorodeoxyglucose positron emission tomography-guided surgery for recurrent colorectal cancer: a feasibility study.

OBJECTIVE: Positron emission tomography (PET) scanning is an accepted diagnostic tool for the detection of colorectal cancer (CRC). The purpose of this study was to determine whether diagnostic information offered by preoperative PET scan could be used to detect disease intraoperatively using beta and gamma handheld probes. METHODS: Two studies were carried out. First, tumor "phantoms" were created using 62 microCi fluorodeoxyglucose (FDG) in a saline-filled basin. Gamma and beta handheld probes were used to determine detection characteristics with respect to probe type, distance from source, and isotope half-life. In a second study, probes were used intraoperatively to detect tumor in 10 patients with recurrent colorectal cancer as determined by preoperative PET scan. Counts relative to background were determined for each probe as was histopathologic correlation with probe-positive tissue. RESULTS: Phantom studies documented that FDG detection by each probe was nonlinearly related to source proximity and half-life. In human subjects, abnormal findings on preoperative PET studies were detected by both probes with tumor:normal ratios of 1.6 (beta) and 1.5 (gamma). All probe-positive tissue was histologically confirmed to be recurrent colorectal cancer. CONCLUSIONS: Intraoperative detection of CRC using an FDG source and beta and gamma probes correlates with preoperative PET. With further improvements in probe technology, successful differentiation of normal and tumor tissue as shown here may allow for more precise localization and directed resection.

Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors often metastasize to the liver and present with disabling hormonal symptoms. Hepatic artery chemoembolization (HACE) combined with somatostatin therapy, pre-embolization, peri-embolization and post-embolization, at doses to control symptoms, is an aggressive approach that can relieve hormonal symptoms with minimal morbidity and mortality. METHODS: Chemoembolization was performed using 30 mg of adriamycin, 50 mg of mitomycin, 12 ml of hexabrix, 10 ml of ethiodol, and 360-500-microm particles. Pancreastatin, a split product of chromogranin A, was measured pre-HACE and post-HACE in all patients. RESULTS: Forty-three chemoebolization procedures were performed in 34 symptomatic patients from December 1995 to August 1999. Seventeen patients had intestinal primaries (50%), seven had pancreatic primaries (20%), five had bronchial primaries (15%), and five had unknown primaries (15%). Systemic pancreastatin levels were improved or stable in 31 patients (78%). Symptoms were improved in these 31 patients (78%). Systemic serotonin levels were improved or stable in 24 patients (60%). Radiographic improvement or stability was seen in 18 patients (45%). Procedural related morbidity included pain, fevers, nausea, vomiting, and transient elevations of liver function studies in 75-100% of patients. There was one procedural related mortality (2%). Less than 20% improvement in pancreastatin levels from baseline was associated with death in five of five patients (100%). This was not observed with serotonin levels. CONCLUSION: Measurement of serum pancreastatin levels is an easy and useful method to predict success in patients who undergo HACE plus somatostatin therapy for metastatic neuroendocrine tumors to the liver. This therapeutic approach is effective in relieving symptoms in 78% of patients, with minimal major morbidity or mortality.

NCCN Practice Guidelines for Colorectal Cancer.

The NCCN Colorectal Cancer Guidelines panel believes that a multidisciplinary approach is necessary for the management of the patient with colorectal cancer. The panel endorses the concept that treatment of patients in a clinical trial has priority over standard or accepted therapy. The recommended surgical procedure for resectable colon cancer is an en bloc resection; laparoscopic surgery should be done only in the context of a clinical trial. For patients with stage III disease, 5-FU-based adjuvant therapy is recommended. A patient who has metastatic disease in the liver or lung should be considered for surgical resection if he or she is a candidate for surgery and if surgery can extend survival. Surgery should be followed by adjuvant chemotherapy. The panel advocates a conservative post-treatment surveillance program for colon and rectal carcinoma patients. Serial CEA determinations are appropriate if the patient is a candidate for aggressive surgical resection, should recurrence be detected. Abdominal and pelvic CT scans should be utilized only when there are clinical indications of possible recurrence. Patients whose disease progresses during 5-FU-based therapy should be treated with irinotecan or encouraged to participate in a phase I or phase II clinical trial.

Correlative Whole-Body FDG-PET and Intraoperative Gamma Detection of FDG Distribution in Colorectal Cancer.

Purpose: 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is the superior imaging modality for detection of primary and recurrent colorectal cancer compared to magnetic resonance imaging (MRI) or computerized tomography (CT). We investigated the feasibility of developing intraoperative procedures for detection of FDG in tumor deposits in order to assist the surgeon in achieving an optimal reduction of tumor burden.Procedures: Fourteen patients (45-83 years of age) were scanned using FDG-PET followed by Gamma Detection Probe evaluation at laparotomy. One patient did not have a pre-operative FDG-PET scan. The collimated detector probe contained a CdZnTe crystal (7mm diameter x 2mm thick). We used a lower window setting of 200 KeV and an open upper window setting. Fasted patients were given an IV bolus of FDG (4.0-5.7 mCi) 15-20 minutes prior to preparation for surgery. Catheterization and the diuretic Lasix were used to remove FDG activity from the bladder. The time from FDG injection to intraoperative GDP data acquisition varied from 58-110 minutes.Results: In all patients, the GDP detected background activity in normal tissues (aorta, colon, liver, kidney, abdominal wall, mesentery, and urinary bladder). The GDP correctly identified single or multiple tumor foci in 13/14 patients as noted by an audible signal from the control unit (3 S.D. above counts obtained from normal tissues). These tumor foci corresponded to regions of high FDG uptake as seen on FDG-PET scans. The one case that the GDP did not localize was a recurrent mucin pseudomyxoma-producing tumor (acellular, mucinous deposits). Ex vivo GDP evaluations demonstrated significant tumor:normal adjacent tissue activity (audible signals in 6/6 tumor samples tested).Conclusions: These data demonstrate that tumors identified from pre-operative whole-body PET scans can be localized during surgery utilizing a gamma probe detector and FDG.

Delirium in patients with cancer at the end of life.

PURPOSE: Delirium is a common and distressing syndrome seen in patients with advanced cancer. Behavioral manifestations of delirium, such as agitation, may result in medical intervention, stress to family caregivers, and inpatient hospice admission. The purpose of this study was to examine the frequency, characteristics, and presumed causes of delirium in patients with advanced cancer. DESCRIPTION OF STUDY: Records of all patients with cancer who were admitted to an inpatient hospice facility in 1995 were reviewed retrospectively (N = 210). Patients were classified as delirious based on the clinical judgment of the admitting physician. RESULTS: Delirium was the third most common reason for admission (20%). Male gender (P = .04) and the presence of a primary or metastatic brain tumor (P = .03) were significant risk factors for delirium, while advanced age and primary or metastatic liver, lung, or bone cancer were not. Resolution of the agitation, the most disruptive symptom of delirium, occurred in 69% of patients before death or discharge. CLINICAL IMPLICATIONS: Delirium is common in hospice patients with cancer and is an important cause of family distress and increased cost of care. The recognition of early clinical signs and predisposing factors should facilitate prompt diagnosis. Appropriate intervention is usually successful in alleviating the most distressing symptoms of delirium.

Intraoperative electron beam radiotherapy in recurrent colorectal carcinoma.

BACKGROUND AND OBJECTIVES: The installation of a dedicated linear accelerator in a shielded operating room in 1992 allowed us to start a feasibility study of intraoperative electron beam radiation therapy (IOERT) in colorectal carcinoma. METHODS: From March 1992 to February 1996, 28 patients with recurrent colorectal carcinoma were treated with maximal surgical resection and IOERT to the pelvis (n = 20) or paraortics (n = 8). IOERT dose ranged from 10 to 20 Gy with electron energies of 6-15 MeV. Postoperative external beam radiation therapy (EBRT) of 45-50 Gy was planned for the previously unirradiated patients. RESULTS: IOERT was well tolerated, but 10 (70%) of 13 patients in the previously unirradiated group did not complete the EBRT per protocol. Eight patients (29%) had some morbidity including surgically related fistula distal from IOERT sites. Two patients developed pelvic pain, which can be attributed to IOERT. Three-year local control at sites treated with IOERT was 40% (53% for previously irradiated patients and 27% for previously unirradiated patients). The 3-year actuarial overall survival was 12% (17% for previously irradiated patients and 8% for previously unirradiated patients). CONCLUSIONS: Our initial experience showed that it was feasible to treat poor prognostic colorectal cancer patients with IOERT. The morbidity observed was mainly related to extensive surgery in high-risk patients. Poor local control was obtained in patients treated with low-dose IOERT alone. Hence, previously unirradiated patients are encouraged to complete the planned EBRT or, alternatively, are considered for EBRT preoperatively or are given a higher IOERT dose (up to 20 Gy) if EBRT will not be given. Since IORT doses >20 Gy are associated with nerve toxicity, we currently add limited dose EBRT in the previously irradiated group. Patients with disease located in multiple abdominal sites are no longer considered candidates for IOERT.