Opioid initiation timing and palliative care referrals in advanced cancer: retrospective study.

OBJECTIVES: Early opioid initiation is recommended for advanced cancer pain, however the timing of opioid commencement in relation to diagnosis has not been described, and the role of palliative care prescribers is unclear. This study aims to determine the timing of opioid initiation by prescriber and cancer type in relation to key timepoints in the cancer illness course (diagnosis, palliative care referral and death). METHODS: This retrospective cohort study included patients at a quaternary cancer centre with incurable advanced cancer of five different subtype groups. Demographics, clinical characteristics, health service use and details of first slow and immediate release opioid prescription are reported. RESULTS: Among 200 patients, median time to first immediate release opioid prescription was 23 days (IQR 1-82) and to slow release opioid prescription was 47 days (IQR 14-155). Most patients (95%, (n=190) were referred to palliative care (median time to referral 54 days (IQR 18-190)). Non-palliative care prescribers initiated slow release opioids for half the cohort (49%, n=97) prior to referral. Patients with pancreatic cancer had the shortest time to slow/immediate release opioid prescription (median 10 days (IQR 0-39) and 26 days (IQR 1-43) respectively) and shortest survival (median 136 days (IQR 82-214)). CONCLUSIONS: Median time to opioid commencement was approximately 3 weeks after diagnosis. Despite early palliative care involvement, opioid initiation by non-palliative care clinicians was common and remains important. Timely palliative care referral for those with pancreatic cancer may include consideration of earlier complex pain presentations and shorter prognosis.

Movement-related increases in subthalamic activity optimize locomotion.

The subthalamic nucleus (STN) is traditionally thought to restrict movement. Lesion or prolonged STN inhibition increases movement vigor and propensity, while ontogenetic excitation typically has opposing effects. Subthalamic and motor activity are also inversely correlated in movement disorders. However, most STN neurons exhibit movement-related increases in firing. To address this paradox, STN activity was recorded and manipulated in head-fixed mice at rest and during self-initiated treadmill locomotion. The majority of STN neurons (type 1) exhibited locomotion-dependent increases in activity, with half encoding the locomotor cycle. A minority of neurons exhibited dips in activity or were uncorrelated with movement. Brief optogenetic inhibition of the dorsolateral STN (where type 1 neurons are concentrated) slowed and prematurely terminated locomotion. In Q175 Huntington's disease mice abnormally brief, low-velocity locomotion was specifically associated with type 1 hyperactivity. Together these data argue that movement-related increases in STN activity contribute to optimal locomotor performance.

The role of multiple sclerosis subtype in microvascular decompression outcomes for patients with trigeminal neuralgia.

OBJECTIVES: While patients with concomitant trigeminal neuralgia (TN) and multiple sclerosis (MS) are understood to experience a more intractable pain phenotype, whether TN pain outcomes differ by the presenting MS subtype is not well characterized. This study's objective is to compare post-operative pain and numbness outcomes following microvascular decompression (MVD) in TN patients with either relapsing-remitting MS (RRMS) or progressive MS. METHODS: We retrospectively reviewed all TN patients who underwent MVDs at our institution from 2007 to 2020. Of the 1044 patients reviewed, 45 (4.3%) patients with MS were identified. Patient demographics, procedural characteristics, and post-operative pain and numbness scores were recorded and compared. Factors associated with pain recurrence were assessed using survival analyses and multivariate regressions. RESULTS: Of the resulting 45 MS patients, 34 (75.6%) patients presented with the RRMS subtype, whereas 11 (24.4%) patients exhibited progressive MS. Using an adjusted multivariate ordinal regression, the subtype of MS was not significantly associated with the Barrow Neurological Institute (BNI) pain score at final follow-up. Using a Kaplan-Meier survival analysis and a multivariate Cox proportional hazards regression, respectively, RRMS was significantly associated with a shorter post-operative pain-free interval (p = 0.04) as well as a greater risk for pain recurrence (p = 0.02). CONCLUSIONS: Although the degree of pain at final follow-up may not differ, RRMS patients are at increased risk for pain recurrence following MVD for TN. These results align with a growing understanding that neuroinflammation may play a significant role in TN pain.

Emergency Department Use Across Income Groups Following an Increase in Cost-Sharing.

Importance: To encourage the appropriate utilization of emergency care, cost-sharing for emergency care was increased from HK$100 (US $12.8) to HK$180 (US $23.1) per visit in June 2017 in all public hospitals in Hong Kong. However, there are concerns that this increase could deter appropriate emergency department (ED) visits and be associated with income-related disparities. Objective: To examine changes in ED visits after the fee increase. Design, Setting, and Participants: This retrospective cohort study used administrative data from June 2015 to May 2019 from all public hospitals in Hong Kong. Participants included all Hong Kong residents aged 64 years and younger, categorized into low-income, middle-income, and high-income groups according to the median household income in their district of residence. Data analysis was performed from May to June 2023. Main Outcomes and Measures: The primary outcome was the ED visit rate per 100 000 people per month, categorized into 3 severity levels (emergency, urgent, and nonurgent). Secondary outcomes include general outpatient (GOP) visit rate, emergency admission rate, and in-hospital mortality rate per month at public hospitals. Segmented regression analyses were used to estimate changes in the level and slope of outcome variables before and after the fee increase. Results: This study included a total of 5 441 679 ED patients (2 606 332 male patients [47.9%]; 2 108 933 patients [38.5%] aged 45-64 years), with 2 930 662 patients (1 407 885 male patients [48.0%]; 1 111 804 patients [37.9%] aged 45-64 years) from the period before the fee increase. The fee increase was associated with an 8.0% (95% CI, 7.1%-9.0%) immediate reduction in ED visits after June 2017, including a 5.9% (95% CI, 3.3%-8.5%) reduction in urgent visits and an 8.9% (95% CI, 8.0%-9.8%) reduction in nonurgent visits. In addition, a 5.7% (95% CI, 4.7%-6.8%) reduction of emergency admissions was found, whereas no significant changes were observed in in-hospital mortality. Specifically, a statistically significant increase in GOP visits (4.1%; 95% CI, 0.9%-7.2%) was found within the low-income group, but this association became insignificant after controlling for the social security group, who were exempted from payment, as a control. Conclusions and Relevance: In this cohort study, the fee increase was not associated with changes in ED visits for emergency conditions, but there was a negative and significant association with both urgent and nonurgent conditions across all income groups. Considering the marginal increase in public GOP services, further study is warranted to examine strategies to protect low-income people from avoiding necessary care.

Prevalence, Severity, and Predictors of Insomnia in Advanced Colorectal Cancer.

CONTEXT: Insomnia is an under-recognized and undertreated symptom in palliative care and advanced cancer cohorts. Insomnia in an advanced colorectal cancer cohort is yet to be investigated despite colorectal cancer being the third commonest cancer worldwide and one with a high symptom burden. OBJECTIVES: To examine the prevalence of insomnia and its associations in a large advanced colorectal cancer cohort. METHODS: A consecutive cohort study of 18,302 patients with colorectal cancer seen by palliative care services across various settings (inpatient, outpatient, and ambulatory) was conducted from an Australia-wide database (2013-2019). The Symptom Assessment Score (SAS) was used to assess the severity of insomnia. Clinically significant insomnia was defined as SAS score ≥3/10, and used to compare associations with other symptoms and functional scores from validated questionnaires. RESULTS: The prevalence of any insomnia was 50.5%, and clinically significant insomnia 35.6%, particularly affecting people who were younger (<45-years-old), more mobile (AKPS score ≥70), or physically capable (RUG-ADL score ≤5). Outpatients and patients living at home had higher prevalence of insomnia. Nausea, anorexia and psychological distress were the commonest concurrent symptoms in patients with clinically significant insomnia. CONCLUSIONS: To our knowledge, this study was the first to investigate the prevalence and associations of insomnia in an advanced colorectal cancer cohort. Our findings demonstrate several groups at greater risk of suffering from insomnia (younger, greater physical capacity, living at home, and those with greater psychological distress). This may guide earlier recognition and management of insomnia to improve overall quality of life in this population.

Short-term Western-style diet negatively impacts reproductive outcomes in primates.

A maternal Western-style diet (WSD) is associated with poor reproductive outcomes, but whether this is from the diet itself or underlying metabolic dysfunction is unknown. Here, we performed a longitudinal study using regularly cycling female rhesus macaques (n = 10) that underwent 2 consecutive in vitro fertilization (IVF) cycles, one while consuming a low-fat diet and another 6-8 months after consuming a high-fat WSD. Metabolic data were collected from the females prior to each IVF cycle. Follicular fluid (FF) and oocytes were assessed for cytokine/steroid levels and IVF potential, respectively. Although transition to a WSD led to weight gain and increased body fat, no difference in insulin levels was observed. A significant decrease in IL-1RA concentration and the ratio of cortisol/cortisone was detected in FF after WSD intake. Despite an increased probability of isolating mature oocytes, a 44% reduction in blastocyst number was observed with WSD consumption, and time-lapse imaging revealed delayed mitotic timing and multipolar divisions. RNA sequencing of blastocysts demonstrated dysregulation of genes involved in RNA binding, protein channel activity, mitochondrial function and pluripotency versus cell differentiation after WSD consumption. Thus, short-term WSD consumption promotes a proinflammatory intrafollicular microenvironment that is associated with impaired preimplantation development in the absence of large-scale metabolic changes.

Severe infections remain common in a real-world rheumatoid arthritis cohort: A simple clinical model to predict infection risk.

OBJECTIVE: This study aimed to investigate the incidence of severe infections in patients of a dedicated rheumatoid arthritis (RA) clinic, identify the associated risk factors, and derive an infection risk screening tool. METHODS: Between January and July 2019, 263 eligible patients with a diagnosis of RA were recruited retrospectively and consecutively from an RA clinic of an Australian tertiary hospital. The primary outcome was severe infection (requiring hospital admission) between January 2018 and July 2019. We collected data from medical records and pathology results. We used validated scores, such as the disease activity score of 28 joints (DAS28) and the Charlson comorbidity index, to assess the disease activity and comorbidity burden. Multivariable logistic regression was used for statistical analysis. RESULTS: A total of 45 severe infection episodes occurred in 34 (13%) patients, corresponding to 10.8 infections per 100 patient-years. Respiratory (53%) and urinary (13%) tract infections were the most common. In the multivariable analysis, significant risk factors included low lymphocyte count (odds ratio [OR], 4.08; 95% confidence interval [CI], 1.16-14.29), severe infection in the past 3 years (OR, 3.58; 95% CI, 1.28-9.97), Charlson comorbidity index >2 (OR, 2.69; 95% CI, 1.03-7.00), and higher DAS28 (OR, 1.35/0.5-unit increment; 95% CI, 1.10-1.67). A model incorporating these factors and age had an area under receiver operating characteristic curve of 0.82. CONCLUSION: To the best of our knowledge, this was one of the first Australian studies to evaluate severe infection rates in a real-world RA cohort. The rates remained high and comparable with those of the older studies. Lymphopenia, disease activity, comorbidity burden, and previous severe infection were the independent risk factors for infection. A model comprising easily assessable clinical and biological parameters has an excellent predictive potential for severe infection. Once validated, it may be developed into a screening tool to help clinicians rapidly identify the high-risk patients and inform the tailored clinical decision making.

Who is afraid of biosimilars? Openness to biosimilars in an Australian cohort of patients with rheumatoid arthritis.

Biosimilars are increasingly adopted to improve affordability of biologics. An effective introduction of biosimilars requires an understanding of patient acceptance of these agents. We performed a cross-sectional study of 132 patients with rheumatoid arthritis prior to the introduction of biosimilar switching or prescribing in this cohort. Despite being unfamiliar with biosimilars, most patients are willing to accept biosimilar medicines if recommended by their rheumatologist. Patient concerns about biosimilar uptake mainly focus on concerns about its efficacy. There is a significant correlation between patient attitudes towards biosimilar and generic medicines.

Improving Heart Failure Outcomes in Ambulatory and Community Care: A Scoping Study.

Despite a large body of literature testing interventions to improve heart failure care, care is often suboptimal. This scoping study assesses organizational interventions to improve heart failure outcomes in ambulatory settings. Fifty-two studies and systematic reviews assessing multicomponent, self-management support, and eHealth interventions were included. Studies dating from the 1990s demonstrated that multicomponent interventions could reduce hospitalizations, readmissions, mortality, and costs and improve quality of life. Self-management support appeared more effective when included in multicomponent interventions. The independent contribution of eHealth interventions remains unclear. No studies addressed management of comorbidities, geriatric syndromes, frailty, or end of life care. Few studies addressed risk stratification or vulnerable populations. Limited reporting about intervention components, implementation methods, and fidelity presents challenges in adapting this literature to scale interventions. The use of standardized reporting guidelines and study designs that produce more contextual evidence would better enable application of this work in health system redesign.

Serotonin syndrome following methylene blue administration during cardiothoracic surgery.

INTRODUCTION: Despite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. We report a case of serotonin syndrome following methylene blue administration in a cardiothoracic surgery patient. CASE REPORT: A 59-year-old woman taking preoperative venlafaxine and trazodone was given a single dose of 2 mg/kg methylene blue (167 mg) during a planned coronary artery bypass and mitral valve repair. Postoperatively, she was febrile to 38.7°C and developed full-body tremors, rhythmic twitching of the perioral muscles, slow conjugate roving eye movements, and spontaneous movements of the upper extremities. Electroencephalography revealed generalized diffuse slowing consistent with toxic encephalopathy, and a computed tomography scan showed no acute process. The patient's symptoms were most consistent with a methylene blue-induced serotonin syndrome. Her motor symptoms resolved within 48 hours and she was eventually discharged home. DISCUSSION: Only 2 cases of methylene blue-induced serotonin syndrome during cardiothoracic surgery have been described in the literature, with this report representing the third case. Methylene blue and its metabolite, azure B, are potent, reversible inhibitors of monoamine oxidase A which is responsible for serotonin metabolism. Concomitant administration of methylene blue with serotonin-modulating agents may precipitate serotonin syndrome.

Active video gaming in patients with renal transplant: a pilot study.

BACKGROUND: Patients with renal transplant are at higher risk of mortality from cardiovascular disease (CVD) compared with the general population. Physical activity has been shown to reduce the risk of CVD mortality in these patients. Unfortunately, barriers such as the harsh Canadian climate prevent patients from engaging in and harvesting the health benefits of physical activity. This pilot study explored active video gaming (AVG) as a way for patients with renal transplant to obtain physical activity and examined its effect on their functional status and quality of life (QOL). MAIN TEXT: We recruited nine patients for an 8-week prospective pilot study. All patients received a Microsoft Xbox 360™ video gaming console, a Microsoft Kinect™ sensor, and the video game Your Shape Fitness Evolved 2012. Assessment of each participant before and after the intervention included blood pressure measures, a 6-minute walk test, and the Godin Leisure Time Questionnaire (GLTQ). We analyzed all nine patients at the end of the 8-week study period, and found no changes in blood pressure or GLTQ scores. However, there was a significant increase in the 6-minute walk distance (P = 0.022), which represented a consistent increase for most patients (correlation = 0.977). In addition, participants over the age of 45 years (n = 4) were more likely to use the AVG system (P = 0.042). CONCLUSION: AVG has the potential to improve the functional status in patients with renal transplant. Further research is required to corroborate the full health benefits of AVG in this patient population.

Docetaxel-associated palmar-plantar erythrodysesthesia: a case report and review of the literature.

Docetaxel-associated palmar-plantar erythrodysesthesia is rarely reported in literature, particularly when used in the treatment of sarcomas. Here, we report a case of docetaxel-related palmar-plantar erythrodysesthesia in a 28-year-old male with recurrent Ewing sarcoma. Although palmar-plantar erythrodysesthesia has been seen in the literature for 30 years, there has still been little progress in understanding and appropriately addressing this adverse effect. This case report and literature review illustrates an infrequently documented adverse skin reaction and discusses the etiology, presentation, and available treatment options for palmar-plantar erythrodysesthesia.

Epithelial healing and visual outcomes of patients using omega-3 oral nutritional supplements before and after photorefractive keratectomy: a pilot study.

PURPOSE: To investigate the effect of omega-3 oral nutritional supplementation on corneal reepithelialization, visual acuity, and tear stability after photorefractive keratectomy (PRK). METHODS: This is a prospective, randomized, single-blinded controlled therapeutic trial using omega-3 oral nutritional supplements (TheraTears Nutrition for Dry Eyes; Advanced Vision Research-Akorn, Ann Arbor, MI) conducted at our center. Eighteen healthy patients with refractive error between -1 and -8 diopters were recruited and had bilateral PRK. The treatment group (n = 9 subjects) received omega-3 2 weeks before surgery through 1 month after PRK. The control group (n = 9 subjects) was not given omega-3. Epithelial defects were photographed on postoperative days 0 to 5. Reepithelialization (area in square millimeters) was assessed by fluorescein staining until healing. Tear breakup time (TBUT) and uncorrected distance visual acuity were measured at 1 week, and 1 and 3 months postoperatively. RESULTS: Epithelial defect in the treatment group eyes healed faster compared with that of the controls (P = 0.04). The treatment group eyes healed at an average rate of 1.19% [SD = 0.002; 95% confidence interval (CI), 1.04%-1.34%] per hour, versus 0.83% (SD = 0.0008; 95% CI, 0.77%-0.89%) for controls (Mann-Whitney rank-sum test, P < 0.001). The treatment group eyes maintained a significantly longer TBUT from week 1 through 3 months (mean = 9.52 seconds, SD = 0.81; 95% CI, 8.93-10.10), compared with the controls (mean = 5.52 seconds, SD = 0.81; 95% CI, 4.93-6.10; P < 0.001), and all reached 20/20 vision versus only 4 in the control group 1 month after surgery (P = 0.03). CONCLUSIONS: Omega-3 oral nutritional supplements decreased the average time for epithelial healing, and improved TBUT and visual acuity recovery in PRK. These findings suggested that omega-3 oral nutritional supplementation may be a beneficial adjunct therapy for PRK patients.

Fully distributed fiber-optic temperature sensing using acoustically-induced rocking grating.

A highly sensitive fully distributed fiber-optic temperature sensing technique is proposed and demonstrated based on a transient and traveling rocking grating. The rocking grating is generated by pulsed acoustic torsional waves propagating along the fiber. The measured temperature sensitivity is 1000 ppm/°C and is experimentally demonstrated mainly due to the temperature dependence of the fiber birefringence. This traveling rocking grating based sensing technique may also serve other fully-distributed sensing applications by using specially designed fibers.

Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell carcinoma in vitro and in xenografts through the inhibition of nuclear factor kappaB by an AKT-independent pathway.

PURPOSE: The purpose of this study was to determine whether a liposomal formulation of curcumin would suppress the growth of head and neck squamous cell carcinoma (HNSCC) cell lines CAL27 and UM-SCC1 in vitro and in vivo. EXPERIMENTAL DESIGN: HNSCC cell lines were treated with liposomal curcumin at different doses and assayed for in vitro growth suppression using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A reporter gene assay was done on cell lines to study the effect of liposomal curcumin on nuclear factor kappaB (NFkappaB) activation. Western blot analysis was done to determine the effect of curcumin on the expression of NFkappaB, phospho-IkappaBalpha, phospho-AKT (pAKT), phospho-S6 kinase, cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S. Xenograft mouse tumors were grown and treated with intravenous liposomal curcumin. After 5 weeks, tumors were harvested and weighed. Immunohistochemistry and Western blot analyses were used to study the effect of liposomal curcumin on the expression of NFkappaB and pAKT. RESULTS: The addition of liposomal curcumin resulted in a dose-dependent growth suppression of both cell lines. Liposomal curcumin treatment suppressed the activation of NFkappaB without affecting the expression of pAKT or its downstream target phospho-S6 kinase. Expression of cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S were reduced, indicating the effect of curcumin on the NFkappaB pathway. Nude mice xenograft tumors were suppressed after 3.5 weeks of treatment with i.v. liposomal curcumin, and there was no demonstrable toxicity of liposomal curcumin upon autopsy. Immunohistochemistry and Western blot analysis on xenograft tumors showed the inhibition of NFkappaB without affecting the expression of pAKT. CONCLUSIONS: Liposomal curcumin suppresses HNSCC growth in vitro and in vivo. The results suggest that liposomal curcumin is a viable nontoxic therapeutic agent for HNSCC that may work via an AKT-independent pathway.

Neurophysiological actions of methylphenidate in the primary somatosensory cortex.

As a catecholamine reuptake blocker, methylphenidate (MPH) enhances noradrenergic transmission and is likely to influence norepinephrine actions in sensory systems. To characterize neurophysiological actions of MPH in the primary somatosensory (SI) cortex, we recorded basal and whisker deflection-evoked discharge of infragranular sensory cortical neurons, before and after intraperitoneal administrations of saline and MPH (5 mg/kg) in halothane-anesthetized rats. MPH had two types of actions on sensory-evoked neuronal responses in the SI cortex, depending on the initial amplitude of the sensory response. When the whisker deflection induced a small excitatory response under control conditions, MPH significantly increased the amplitude of the response by approximately 40%. When the whisker stimulation induced a large excitatory response under control conditions, MPH did not significantly alter the amplitude of the response, but significantly decreased the duration and the peak latency of the response, so that the response was more focused. These neurophysiological actions of MPH may underlie some of the beneficial effects of the drug on sensory processing and attention.

Investigación en el sistema da Vinci en el hospital St Mary's de Londres / Investigation in the system da Vinci in the hospital St Mary' s of London

Hipótesis: El sistema robótico da Vinci™ permite superar las limitaciones que impone al cirujano la cirugía mínimamente invasora en términos de destreza, control del campo operatorio y ergonomía.Los estudios incluidos en esta compilación evalúan la curva de aprendizaje, la visión en tercera dimensión y el análisis de movimientos, con el propósito de comprobar las ventajas del sistema da Vinci sobre la cirugía mínimamente invasora y establecer métodos de evaluación de desempeño. Métodos: Sistema: da Vinci™. Tres estudios experimentales comparativos con diez y trece cirujanos quienes realizaron diferentes pruebas. Estudiaron: curva de aprendizaje entre cirujanos experimentados/ no experimentados, ventajas de visión 3D sobre 2D y de cirugía robótica (CR) sobre cirugía mínimamente invasora. Evaluación de mediciones: el desempeño de los cirujanos se midió con una escala global de habilidades y medición de errores. Calificación: a ciegas por expertos; además se empleó un software de análisis de movimiento para cirugía mínimamente invasora y para cirugía robótica, ambos desarrollados en el departamento y previamente validados en otros estudios. Cálculos estadísticos: programa Statistical Package for Social Sciences 10,0™. p<0,05.Resultados: La curva de aprendizaje reveló un puntaje de valoración objetiva y estructurada de destrezas técnicas de 18 (primer intento) contra 26 (quinto) p=0,02 Cronbach µ=0,894. El análisis de movimiento mostró reducción del numero de movimientos y trayectoria (p>0,01). La comparación de cirugía mínimamente invasora con cirugía robótica mostró reducción del 40 por ciento del tiempo (p=0,001) y de 70 por ciento de la trayectoria (p=0,008) con reducción de 93 por ciento de errores. La visión 3D demostró ser superior a 2D en esta y otras pruebas. La comparación entre cirugía laparoscópica y robótica en dos estudios mostró ventajas para el da Vinci.Conclusión: Los instrumentos articulados, la abolición del temblor, los movimientos a escala reducida y la visión 3D del da Vinci mejoran la habilidad y desempeño del cirujano en cirugía mínimamente invasora asistida por robot...

Genetic abnormalities associated with nodal metastasis in head and neck cancer.

BACKGROUND: Lymphatic metastasis represents the single most important clinical prognostic factor in head and neck squamous cell carcinoma (HNSCC), but underlying genetic mechanisms remain ill defined. Genetic differences between primary carcinomas and their corresponding metastases might form a key to understanding the metastatic phenotype. In this study we aimed to characterize such differences using a genome-wide screening measure. METHODS: Four human cell lines (MDA-686tu, MDA-686Ln, MDA-1386tu, MDA-1386Ln) derived from primary tumor and synchronous lymph node metastasis of two cases of metastatic HNSCC were subjected to comparative genomic hybridization (CGH) by differentially labeling DNA from tumor tissue and normal tissue with fluorescent agents. The labeled DNAs were simultaneously hybridized onto normal metaphase chromosomes. In addition, modified CGH was performed by directly hybridizing labeled primary tumor DNA against differentially labeled metastatic tumor DNA, allowing the direct detection of copy number differences in individual pairs. Image analysis for fluorescence intensity along the entire length of each metaphase chromosome allowed generation of a color ratio, which was used to detect copy number changes. RESULTS: In both cases, significant overlap was found between chromosomal aberrations present in the primary tumor and the corresponding nodal metastasis. However, several abnormalities differentiated primary tumors from their metastases. Modified CGH identified several genetic aberrations that were not detectable with the conventional CGH analysis. Gains at chromosomes 10p11-12 and 11p and deletions at chromosomes 4q22-31, 9p13-24, and 14q differentiated nodal metastases from the corresponding primary tumors in both cases. CONCLUSIONS: The combination of conventional and modified CGH analyses facilitates the identification of DNA copy number changes that might be involved in the development of a metastatic phenotype. Future research should aim at the identification of the genes involved at the identified sites of chromosomal aberration.