EEG Correlates of Central Origin of Cancer-Related Fatigue.

The neurophysiological mechanism of cancer-related fatigue (CRF) remains poorly understood. EEG was examined during a sustained submaximal contraction (SC) task to further understand our prior research findings of greater central contribution to early fatigue during SC in CRF. Advanced cancer patients and matched healthy controls performed an elbow flexor SC until task failure while undergoing neuromuscular testing and EEG recording. EEG power changes over left and right sensorimotor cortices were analyzed and correlated with brief fatigue inventory (BFI) score and evoked muscle force, a measure of central fatigue. Brain electrical activity changes during the SC differed in CRF from healthy subjects mainly in the theta (4-8 Hz) and beta (12-30 Hz) bands in the contralateral (to the fatigued limb) hemisphere; changes were correlated with the evoked force. Also, the gamma band (30-50 Hz) power decrease during the SC did not return to baseline after 2 min of rest in CRF, an effect correlated with BFI score. In conclusion, altered brain electrical activity during a fatigue task in patients is associated with central fatigue during SC or fatigue symptoms, suggesting its potential contribution to CRF during motor performance. This information should guide the development and use of rehabilitative interventions that target the central nervous system to maximize function recovery.

Does reevaluation of colorectal cancers with inadequate nodal yield lead to stage migration or the identification of metastatic lymph nodes?

BACKGROUND: The National Comprehensive Cancer Network recommends routine reevaluation of all stage II colon cancer specimens with fewer than 12 lymph nodes. However, there are few data demonstrating the effect of reevaluation on stage. OBJECTIVE: The aim of this study was to demonstrate the effect of pathologic reevaluation for colorectal cancers with fewer than 12 lymph nodes on stage. DESIGN: This study entailed a retrospective review of pathology reports. SETTINGS: This study was conducted at 2 large multispecialty referral centers. INTERVENTIONS: Pathologic reevaluation was performed to look for additional lymph nodes. PATIENTS: All patients with stage I through III colorectal cancers with inadequate lymph node yields who underwent reevaluation from January 1, 2007 through March 31, 2011 were identified. MAIN OUTCOME MEASURES: We recorded initial pathologic stage and new stage following reevaluation. The following variables before and after reevaluation were also recorded: 1) total lymph node count, 2) metastatic node count, 3) negative node count, and 4) lymph node ratio. RESULTS: Eighty-three patients underwent pathologic reevaluation from a total of 1682 cancer specimens. Mean nodal yields were 7.2 ± 2.6 on the first pathologic review. On reevaluation, 80% of patients had one or more newly identified nodes. On average, 6.9 ± 9.6 more lymph nodes were identified with a metastatic node detected in 4 of 83 patients (4.8%). After pathologic reevaluation, 1 patient (1.2%) had a change in TNM stage from N1 to N2 disease. The lymph node ratio changed in 13 of 15 patients (87% of stage III cancers). Only 4 of these had a change in lymph node quartile. LIMITATIONS: The study was limited by its retrospective nature and small sample size. CONCLUSION: Few patients have a newly discovered metastatic node or stage change following pathologic reevaluation. The effect of pathologic reevaluation on treatment and outcome should be further investigated.

Key factors associated with postoperative complications in patients undergoing colorectal surgery.

BACKGROUND: Surgical outcomes are determined by complex interactions among a variety of factors including patient characteristics, diagnosis, and type of procedure. OBJECTIVE: The aim of this study was to prioritize the effect and relative importance of the surgeon (in terms of identity of a surgeon and surgeon volume), patient characteristics, and the intraoperative details on complications of colorectal surgery including readmission, reoperation, sepsis, anastomotic leak, small-bowel obstruction, surgical site infection, abscess, need for transfusion, and portal and deep vein thrombosis. DESIGN: This study uses a novel classification methodology to measure the influence of various risk factors on postoperative complications in a large outcomes database. METHODS: Using prospectively collected information from the departmental outcomes database from 2010 to 2011, we examined the records of 3552 patients who underwent colorectal surgery. Instead of traditional statistical methods, we used a family of 7000 bootstrap classification models to examine and quantify the impact of various factors on the most common serious surgical complications. For each complication, an ensemble of multivariate classification models was designed to determine the relative importance of potential factors that may influence outcomes of surgery. This is a new technique for analyzing outcomes data that produces more accurate results and a more reliable ranking of study variables in order of their importance in producing complications. PATIENTS: Patients who underwent colorectal surgery in 2010 and 2011 were included. SETTINGS: This study was conducted at a tertiary referral department at a major medical center. MAIN OUTCOME: Postoperative complications were the primary outcomes measured. RESULTS: Factors sorted themselves into 2 groups: a highly important group (operative time, BMI, age, identity of the surgeon, type of surgery) and a group of low importance (sex, comorbidity, laparoscopy, and emergency). ASA score and diagnosis were of intermediate importance. The outcomes most influenced by variations in the highly important factors included readmission, transfusion, surgical site infection, and abscesses. LIMITATIONS: This study was limited by the use of data from a single tertiary referral department at a major medical center. CONCLUSIONS: Body mass index, operative time, and the surgeon who performed the operation are the 3 most important factors influencing readmission rates, rates of transfusions, and surgical site infection. Identification of these contributing factors can help minimize complications.

Decreasing readmissions by focusing on complications and underlying reasons.

BACKGROUND: To analyze demographics and outcomes of patients focusing on 30-day readmission status and identify procedure-specific risk factors. METHODS: Patients undergoing abdominal colorectal surgery (2011-2013) were identified Demographics and outcomes including in-hospital complications were compared based on readmission status. RESULTS: A total of 6637 patients were identified with a mean age of 51.2(±17.1) years. Seven hundred and seventy five(11.7%) patients were readmitted at least once within 30-day. The most common index procedures related to readmission were stoma closure (n = 127/775, 16.4%) and total colectomy (n = 105/775, 13.6%). Readmitted patients had longer length of index hospital stay (LOS)(8.2 ± 5.9 vs 7.9 ± 6.9 days,p < 0.001) and operative time(167 ± 104 vs 144 ± 95 min, p < 0.001), higher intraoperative(2% vs 1%,p = 0.04) and in-hospital complication rates(36% vs 28%,p < 0.001). Main reasons for readmissions were gastrointestinal-related causes(n = 222, 29%), small bowel obstruction (n = 133,17%), wound-related complications(n = 108,14%), and dehydration(n = 93,12%). Median readmission LOS was 4(1-71)days and 54%(n = 407) of readmissions occurred within 7 days of discharge. CONCLUSION: Increased postoperative complications may be the main preventable underlying reason for increased risk of hospital readmission after colorectal surgery. Preventive measures to decrease complications and actions to identify high risk patients for complications would help to reduce readmissions.

Quantification of risk for early unplanned readmission after rectal resection: a single-center study.

BACKGROUND: Several factors predictive of readmission after colorectal surgery have been identified. Although often grouped together in readmission studies, colon and rectal resections differ in many ways. The aim of this study was to identify factors associated with readmission after rectal resection. STUDY DESIGN: We performed a retrospective, single-center cohort study of 565 patients who underwent rectal resections at a tertiary referral center in 2010 and 2011. The main outcomes measure was readmission within 30 days. Univariate comparison between readmitted and nonreadmitted patients was followed by a stepwise logistic regression to identify independent risk factors for readmission. RESULTS: There were 105 patients (18.6%) readmitted. Indication (inflammatory bowel disease [IBD], p = 0.008), type of operation (pelvic pouch surgery, p = 0.02), use of laparoscopy (readmission 27.8% vs 14%, p < 0.001), and length of operation (p < 0.001) were associated with a higher readmission rate on univariate analysis. Neither preoperative chemoradiation (p = 0.89) nor American Society of Anesthesiologists class (p = 0.09) was associated with readmission. Logistic regression showed use of laparoscopy (odds ratio [OR] 1.94, 95% CI 1.23 to 3.07), initial diagnosis of IBD (OR 1.84, 95% CI 1.17 to 2.93), and length of operation (OR 1.09, 95% CI 1.03 to 1.16 per 30 minutes) to be independent risk factors. Risks of readmission were 6.7%, 13.4%, 27.4%, and 27.4% with 0, 1, 2, or 3 positive risk factors, respectively. CONCLUSIONS: Readmission after rectal resection is associated with the indication for surgery and the operative technique used. Optimization of factors related to the underlying pathology and careful appraisal of the operative technique may result in decreased readmission after proctectomy.

Myoelectrical manifestation of fatigue less prominent in patients with cancer related fatigue.

PURPOSE: A lack of fatigue-related muscle contractile property changes at time of perceived physical exhaustion and greater central than peripheral fatigue detected by twitch interpolation technique have recently been reported in cancer survivors with fatigue symptoms. Based on these observations, it was hypothesized that compared to healthy people, myoelectrical manifestation of fatigue in the performing muscles would be less significant in these individuals while sustaining a prolonged motor task to self-perceived exhaustion (SPE) since their central fatigue was more prominent. The purpose of this study was to test this hypothesis by examining electromyographic (EMG) signal changes during fatiguing muscle performance. METHODS: Twelve individuals who had advanced solid cancer and cancer-related fatigue (CRF), and 12 age- and gender-matched healthy controls performed a sustained elbow flexion at 30% maximal voluntary contraction till SPE. Amplitude and mean power frequency (MPF) of EMG signals of the biceps brachii, brachioradialis, and triceps brachii muscles were evaluated when the individuals experienced minimal, moderate, and severe fatigue. RESULTS: CRF patients perceived physical "exhaustion" significantly sooner than the controls. The myoelectrical manifestation of muscular fatigue assessed by EMG amplitude and MPF was less significant in CRF than controls. The lower MPF even at minimal fatigue stage in CRF may indicate pathophysiologic condition of the muscle. CONCLUSIONS: CRF patients experience less myoelectrical manifestation of muscle fatigue than healthy individuals near the time of SPE. The data suggest that central nervous system fatigue plays a more important role in limiting endurance-type of motor performance in patients with CRF.

Lack of muscle contractile property changes at the time of perceived physical exhaustion suggests central mechanisms contributing to early motor task failure in patients with cancer-related fatigue.

CONTEXT: Fatigue is one of the most common symptoms reported by cancer survivors, and fatigue worsens when patients are engaged in muscle exertion, which results in early motor task failure. Central fatigue plays a significant role, more than muscle (peripheral) fatigue, in contributing to early task failure in cancer-related fatigue (CRF). OBJECTIVES: The purpose of this study was to determine if muscle contractile property alterations (reflecting muscle fatigue) occurred at the end of a low-intensity muscle contraction to exhaustion and if these properties differed between those with CRF and healthy controls. METHODS: Ten patients (aged 59.9±10.6 years, seven women) with advanced solid cancer and CRF and 12 age- and gender-matched healthy controls (aged 46.6±12.8 years, nine women) performed a sustained contraction of the right arm elbow flexion at 30% maximal level until exhaustion. Peak twitch force, time to peak twitch force, rate of peak twitch force development, and half relaxation time derived from electrical stimulation-evoked twitches were analyzed pre- and post-sustained contraction. RESULTS: CRF patients reported significantly greater fatigue as measured by the Brief Fatigue Inventory and failed the motor task earlier, 340±140 vs. 503±155 seconds in controls. All contractile property parameters did not change significantly in CRF but did change significantly in controls. CONCLUSION: CRF patients perceive physical exhaustion sooner during a motor fatigue task with minimal muscular fatigue. The observation supports that central fatigue is a more significant factor than peripheral fatigue in causing fatigue feelings and limits motor function in cancer survivors with fatigue symptoms.

Review article: a systematic review of cancer-related fatigue measurement questionnaires.

PURPOSE: Cancer-related fatigue (CRF) is a common symptom experienced by patients in all stages and in cancer survivors. The main objectives of this review were to identify validated CRF instruments, and populations in whom these tools have been validated. METHODS: We used a systematic review methodology. Three separate searches were performed using different MeSH terms in Pub Med and Ovid databases. Articles were analyzed for validation and reliability. RESULTS: A total of 1453 papers from 3 different searches identified 40 instruments (3 unidimensional and 37 multidimensional). Instruments varied by psychometric properties, items, scale, dimension, cancer site, and population. Five were optimally tested for validity and reliability. Completion rates, sensitivity to change, and test-retest reliability were reported for a few. DISCUSSION: Most tools had been validated in mixed populations and are relatively insensitive to differences in fatigue to cancer stage. Most instruments are burdensome for those with advanced cancer. The Brief Fatigue Inventory and 3 fatigue items of the European Organization for Research and Treatment Quality of Life Questionnaire Fatigue Scale (EORTC QLQ-C30) are optimal instruments in advanced cancer. CONCLUSIONS: In all, 40 CRF instruments were identified. Validity and reliability varied by questionnaire. The ideal item numbers, scale, and domains are not established and may be population dependent.

Fatigue in advanced cancer: a prospective study.

Fatigue is a common advanced cancer symptom. Clinical features are not well known. The authors surveyed consecutive patients admitted to a palliative medicine program to identify clinical correlates of fatigue. Data collected included age, sex, performance status, primary site, prior chemotherapy/radiation therapy, and blood transfusions. Visual analogue scales assessed fatigue, quality of life, and ability to perform daily activities. Weight change was estimated. Laboratory results including lactate dehydrogenase and hemoglobin were recorded. Fatigue severity was associated with brain metastases, poor performance status, poor quality of life, and reduced ability to perform activities. Prior radiation therapy was associated with less severe fatigue. Age, sex, and hemoglobin level were not associated with fatigue. Fatigue was universal on referral. Brain metastases and poor quality of life independently predicted severity. Hemoglobin level did not predict fatigue. Further studies are necessary to define the clinical features and relationships of fatigue.