Feasibility and Safety of Ambulatory Surgery as the Next Management Paradigm in Colorectal Resection Surgery.

BACKGROUND: Current clinical dogma favors universal inpatient admission after colorectal resection particularly in the presence of an anastomosis. OBJECTIVE: We evaluate the feasibility and safety of ambulatory surgery in carefully selected patients undergoing colorectal resection/anastomosis. METHODS: Between October 2020 and October 2021, all patients undergoing colorectal resection/anastomosis meeting specific criteria {no major comorbidity [American Society of Anesthesiologist (ASA) <4], not on therapeutic anticoagulation, compliant patient/family} were counseled preoperatively for ambulatory surgery (discharge <24 h postsurgery). Complicated surgery (ileoanal pouch, enterocutaneous fistula repair, reoperative pelvic surgery, multiple resections) and/or ostomy creation (loop/end ileostomy, Hartmann's, abdominoperineal resection) were exclusions. Discharge was at 6 to 8 hours postoperatively if all predetermined factors (no ostomy teaching needed, ambulating comfortably, tolerating diet, stable vitals, and blood-work) were met and patients were willing, or was postponed to the next day at patient request. All discharged patients received phone checks the next day with the option also given for voluntary readmission if inpatient care was preferred by patient. Patients discharged <24 hours postop (AmbC) were compared to those staying on as inpatients admitted (InpC) and also to a comparable historical (October 2019-October 2020) group when ambulatory surgery was not offered (HistC). RESULTS: Of 184 abdominal colorectal surgery patients, 97 had complicated colorectal resection and/or ostomy. Of the remaining 87, 29 (33.3%) were discharged <24 hours postoperatively [7 (24%) patients at 8 h]. Of these 29 AmbC patients, 4 were readmitted <30 days (ileus: 1, rectal bleeding: 2, nausea/vomiting: 1), 1 readmission was on first postdischarge day, none were voluntary post phone-check. AmbC and InpC (n=58) had similar age, sex, race, body mass index, and comorbidity. InpC had greater estimated blood loss (109 vs 34 mL, P <0.001) while length of stay was expectedly significantly longer (109 vs 17 hours, P <0.001). There was no mortality in either group. AmbC and InpC had similar readmission, reoperation, anastomotic leak, ileus, and surgical site infection. Mean length of stay for HistC was 83 hours. AmbC and HistC had similar age, sex, race, body mass index, and ASA class. Complications including readmission, reoperation, anastomotic leak, ileus, and surgical site infection were also similar for AmbC and HistC. CONCLUSIONS: With careful patient selection, preoperative education, perioperative management, and postoperative follow-up, ambulatory surgery is feasible in up to a third of patients undergoing colorectal resection/anastomosis and can be performed with comparable safety to the time-honored practice of routine inpatient hospitalization. Refinements in inclusion/exclusion criteria and postoperative outpatient follow-up will allow a paradigm shift in how such patients are managed, which has huge implications for patient experience, care-giver workload and health care finances.

Effects of Gabapentin Enacarbil on Postoperative Pain After Hip and Knee Arthroplasty: A Placebo-controlled Randomized Trial.

OBJECTIVES: Total joint arthroplasties are among the most common elective procedures performed in the United States, and they are associated with postoperative pain. Gabapentin enacarbil is a prodrug with an extended-release formulation that has been proposed for multimodal postoperative analgesia, but the drug's efficacy for major arthroplasties remains unclear. MATERIALS AND METHODS: We enrolled 60 adult patients scheduled for primary knee or hip arthroplasty expected to remain hospitalized for at least 3 days. Eligible patients were randomly assigned to placebo or gabapentin enacarbil 600 mg twice daily starting the day before surgery continuing for 3 days thereafter.The primary outcome was analyzed using a joint hypothesis framework of pain (0 to 10 verbal response scores) and cumulative opioid consumption (mg of morphine equivalent) within the first 72 hours. Secondary outcomes were nausea and vomiting, pain persisting 90 days after surgery, duration of hospitalization, and early postoperative health status using quality of recovery score (QoR-15). RESULTS: Twenty-eight patient in gabapentin enacarbil group and 32 in placebo group were analyzed. Since pain scores did not differ significantly (difference of means: -0.2 in pain scores; 95% confidence interval: -1.1, 0.7), nor did opioid consumption, conditions for joint hypothesis testing were not met. Moreover, there were no significant differences between groups for secondary outcomes. DISCUSSION: We did not identify statistically significant or clinically meaningful differences in our primary and secondary outcomes related to perioperative use of gabapentin enacarbil in patients having primary hip or knee arthroplasties.

Subcostal Anterior Quadratus Lumborum Block Versus Epidural Block for Analgesia in Open Nephrectomy: A Randomized Clinical Trial.

BACKGROUND: Epidural block are often used for analgesia after open nephrectomy surgery. Subcostal anterior quadratus lumborum block may be an alternative. We therefore tested the hypothesis that the continuous subcostal anterior quadratus lumborum block is noninferior to epidural block for analgesia in patients having open partial nephrectomies. METHODS: Adults having open partial nephrectomies were randomly allocated to epidural or unilateral subcostal anterior quadratus lumborum block. The joint primary outcomes were opioid consumption measured in morphine equivalents and pain measured on a numeric rating scale (0-10) from postanesthesia care unit (PACU) until 72 hours after surgery. The noninferiority deltas were 30% for opioid consumption and 1 point on a 0-10 scale for pain. Secondary outcomes included patient global assessment of pain management on the third postoperative day, the number of antiemetic medication doses through the third postoperative day, duration of PACU stay, and postoperative duration of hospitalization. RESULTS: Twenty-six patients were randomized to anterior quadratus lumborum block and 29 to epidural analgesia. Neither pain scores nor opioid consumption in the quadratus lumborum patients were noninferior to epidural analgesia. At 72 hours, mean ± standard deviation pain scores in subcoastal anterior quadratus lumborum block and epidural group were 4.7 ± 1.8 and 4.1 ± 1.7, with an estimated difference in pain scores of 0.62 (95% confidence interval [CI], 0.74-1.99; noninferiority P = .21). The median [Q1, Q3] opioid consumption was more than doubled in quadratus lumborum patients at 70 mg [43, 125] versus 30 mg [18, 75] in the epidural group with an estimated ratio of geometric means of 1.69 (95% CI, 0.66-4.33; noninferiority P = .80). Patient global assessment and duration of PACU and hospital stays did not differ significantly in the 2 groups. CONCLUSIONS: We were unable to show that subcostal anterior quadratus lumborum block are noninferior to epidural analgesia in terms of pain scores and opioid consumption for open partial nephrectomies. Effectiveness of novel blocks should be rigorously tested in specific surgical setting before widespread adoption.

Bilateral continuous posterior quadratus lumborum block for analgesia after open abdominal surgery: A prospective case series.

The quadratus lumborum (QL) block provides analgesia to the abdominal wall while sparing the side effects of neuraxial blocks. We describe a case series of eight patients treated with a continuous infusion of local anesthetic via bilateral posterior QL catheters infusion block for analgesia after abdominal surgeries. We found that the median duration of the procedure was 26 min and the median opioid consumption over the first postoperative 72 h was 110 mg of morphine equivalents. The bilateral continuous posterior QL block is a feasible analgesic intervention and can be considered as a component of multimodal analgesic pathways.

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.

Incidence of adverse events attributable to bupivacaine liposome injectable suspension or plain bupivacaine for postoperative pain in pediatric surgical patients: A retrospective matched cohort analysis.

BACKGROUND: Surgical wound infiltration with local anesthetics is common as part of multimodal analgesia and enhanced recovery pathways in pediatric surgical patients. Liposomal bupivacaine can provide up to 92 hours of pain relief, and was approved by the U.S Food and Drug Administration for local infiltration in adults. It is also commonly used by pediatric surgeons, but its safety profile in this age group has not been described. AIMS: The aim of this study was to describe the incidence of local anesthetic systemic toxicity syndrome in pediatric surgical patients receiving liposomal bupivacaine compared to plain bupivacaine for surgical wound infiltration. METHODS: We conducted a retrospective, single center, assessor blinded cohort study of pediatric surgical inpatients having open or laparoscopic surgery in the Cleveland Clinic between 2013 and 2017 and receiving wound infiltration with local anesthetics. We compared the incidence of local anesthetic systemic toxicity among those who received any dose of liposomal bupivacaine and those who received plain bupivacaine. Groups were matched 1:2 according to procedure type, age, and physical status score. Local anesthetic systemic toxicity was primarily defined as at least two signs or symptoms possibly related to anesthetic toxicity, as judged by two independent adjudicators blinded to the type of local anesthetic. A sensitivity analysis compared the incidence of a single sign/symptom possibly related to anesthetic toxicity. RESULTS: A total of 924 surgical cases were included in the final analysis (356 liposomal bupivacaine and 568 plain bupivacaine cases). The primary outcome did not occur in any patient. The sensitivity analysis found three cases in the liposomal bupivacaine group and two cases in the plain bupivacaine group having a single sign/symptom possibly related to local anesthetic administration (relative risk 2.4, 95% CI 0.4-14.0, P = 0.38). CONCLUSION: In a cohort of pediatric surgical patients receiving wound infiltration with either plain or liposomal bupivacaine, we identified no cases of local anesthetic systemic toxicity syndrome, and only few patients with any sign or symptom that could potentially be related to local anesthetic toxicity.

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.

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.

Insomnia in patients with advanced cancer.

INTRODUCTION: Insomnia is underrecognized in patients with cancer. By identifying clinical correlations and predisposing factors of insomnia, interventions may be initiated to treat insomnia. METHODS: Consecutive patients referred to palliative medicine services were screened with a single question. Patients answering affirmatively completed the Insomnia Severity Index (ISI). Patients were screened for depression, fatigue, and pain. Spearman correlation was performed for associations. RESULTS: Of 715 consecutive patients, 102 had sleep problems and 64 had clinical insomnia by the ISI criteria. Insomnia correlated with depression (r = .32), pain (r = .29), and tiredness (r = .40) but not with age or precipitating factors. DISCUSSION: Insomnia severity moderately correlates with depression, pain, and tiredness. We found no association of insomnia severity with age or medications. CONCLUSION: Insomnia, pain, depression, and tiredness are a symptom cluster.

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.

Four-item fatigue screen: replacing the Brief Fatigue Index.

INTRODUCTION: To develop a shorter and less burdensome cancer-related fatigue (CRF) questionnaire, the Four-Item Fatigue Scale (FIFS) was tested for validity against the Brief Fatigue Index (BFI). METHODS: On day 1, patients with cancer completed the BFI and FIFS in a random order and the reverse on day 7. Sixty-five patients were needed for an 80% power and a Spearman correlation of .7 or greater. The FIFS was compared with the BFI in fatigue severity and changes in fatigue over time. Bonferroni corrections were made for multiple comparisons with International Classification of Diseases, Tenth Revision (ICD-10) fatigue criteria. RESULTS: Seventy-nine patients were enrolled, 65 patients completed both surveys. Spearman correlation between FIFS and BFI for day 1 was 0.69 (95% confidence interval [CI] 0.50-0.87) and 0.73 (95% CI 0.56-0.90) 1 week later. Fatigue severity did not predict survival with either questionnaire. Brief Fatigue Index severity correlated with ICD-10 items 1, 3, 7, and 10B. Regression analysis showed that on day 7 BFI correlated with ICD-10 items 1, 7, and 10. When the model was adjusted for day 1, only the ICD-10 item 5 correlated well in BFI over 1 week. The ICD-10 items 7 and 10 significantly correlated with day 1 FIFS fatigue changes over 7 days after adjustment for FIFS baseline score. CONCLUSIONS: Four-Item Fatigue Scale has concurrent validity for fatigue using the BFI. The FIFS and BFI correlated modestly over time. Certain ICD-10 items correlated with CRF severity depending on the questionnaire.

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.

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.

Methylphenidate side effects in advanced cancer: a retrospective analysis.

INTRODUCTION: Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults. OBJECTIVES: To evaluate MP-associated symptoms or side effects (S/E). METHODS: Data was collected from 2 published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All 3 reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5, and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. RESULTS: 62 patients were enrolled. Fifty completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most (96%) had improvement in depression and/or fatigue. Among the 62 patients, new symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before MP showed significant improvement during MP therapy. CONCLUSIONS: (1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with MP appeared to improve spontaneously despite continued MP therapy. (3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. (4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.

Cancer-related fatigue: central or peripheral?

To evaluate cancer-related fatigue (CRF) by objective measurements to determine if CRF is a more centrally or peripherally mediated disorder, cancer patients and matched noncancer controls completed a Brief Fatigue Inventory (BFI) and underwent neuromuscular testing. Cancer patients had fatigue measured by the BFI, were off chemotherapy and radiation (for more than four weeks), had a hemoglobin level higher than 10 g/dL, and were neither receiving antidepressants nor were depressed on a screening question. The controls were screened for depression and matched by age, gender, and body mass index. Neuromuscular testing involved a sustained submaximal elbow flexion contraction (SC) at 30% maximal level (30% maximum elbow flexion force). Endurance time (ET) was measured from the beginning of the SC to the time when participants could not maintain the SC. Evoked twitch force (TF), a measure of muscle fatigue, and compound action potential (M-wave), an assessment of neuromuscular-junction transmission were performed during the SC. Compared with controls, the CRF group had a higher BFI score (P<0.001), a shorter ET (P<0.001), and a greater TF with the SC (CRF>controls, P<0.05). This indicated less muscle fatigue. There was a greater TF (P<0.05) at the end of the SC, indicating greater central fatigue, in the CRF group, which failed to recruit muscle (to continue the SC), as well as the controls. M-Wave amplitude was lower in the CRF group than in the controls (P<0.01), indicating impaired neuromuscular junction conduction with CRF unrelated to central fatigue (M-wave amplitude did not change with SC). These data demonstrate that CRF patients exhibited greater central fatigue, indicated by shorter ET and less voluntary muscle recruitment during an SC relative to controls.

Bioelectrical impedance phase angle changes during hydration and prognosis in advanced cancer.

INTRODUCTION: We wished to determine bioelectrical impedance (BIA) correlates before hydration or changes during hydration and determine if these changes were prognostically important. METHODS AND MATERIALS: Fifty eligible patients underwent BIA measurements 3 consecutive days. Laboratory studies (electrolytes, creatinine, and hemoglobin) on day 1; weights and vital signs were recorded. Kaplan-Meier survival estimates were made at 30 and 60 days. Hazard ratios (HRs) based on Cox proportional hazards model were calculated. RESULTS: Weight loss was associated with shorter survival. A higher phase angle (PA) on day 1 predicted longer survival. Increased PA during hydration predicted shorter survival: increased weight during hydration predicted longer survival. DISCUSSION: Higher phase angle before hydration predicts poorer survival and, paradoxically, an increase in phase angle during hydration predicted poorer survival and preexisting intracellular dehydration, cachexia, or poor membrane function. CONCLUSIONS: Phase angle and weight during hydration predict survival in cancer.

Weakening of functional corticomuscular coupling during muscle fatigue.

OBJECTIVE: Recent research has shown dissociation between changes in brain and muscle signals during voluntary muscle fatigue, which may suggest weakening of functional corticomuscular coupling. However, this weakening of brain-muscle coupling has never been directly evaluated. The purpose of this study was to address this issue by quantifying EEG-EMG coherence at times when muscles experienced minimal versus significant fatigue. METHODS: Nine healthy subjects sustained an isometric elbow flexion at 30% maximal level until exhaustion while their brain (EEG) and muscle (EMG) activities were recorded. The entire duration of the EEG and EMG recordings was divided into the first half (stage 1 with minimal fatigue) and second half (stage 2 with severer fatigue). The EEG-EMG coherence and power spectrum in each stage was computed. RESULTS: The power of both EEG and EMG increased significantly while their coherence decreased significantly in stage 2 compared with stage 1 at beta (15-35 Hz) band. CONCLUSIONS: Despite an elevation of the power for both the EEG and EMG activities with muscle fatigue, the fatigue weakens strength of brain-muscle signal coupling at beta frequency band. SIGNIFICANCE: Weakening of corticomuscular coupling may be a major neural mechanism contributing to muscle fatigue and associated performance impairment.

Combining objective and subjective outcomes in cancer-related fatigue: illustrations from a single case report.

Neurophysiologic measurements were made on a patient with multiple lung cancers and severe cancer-related fatigue (CRF) who responded to 5 mg methylphenidate twice daily, titrated to 10 mg twice daily after 2 weeks. She remained at 10 mg twice daily for 8 months. Improvement in severe CRF (Brief Fatigue Inventory score) was associated with normalization of neurophysiologic tests.