Predictors of Clavien-Dindo Grade III-IV or Grade V Complications after Metastatic Spinal Tumor Surgery: An Analysis of Sociodemographic, Socioeconomic, Clinical, Oncologic, and Operative Parameters.

The rate of major complications and 30-day mortality after surgery for metastatic spinal tumors is relatively high. While most studies have focused on baseline comorbid conditions and operative parameters as risk factors, there is limited data on the influence of other parameters such as sociodemographic or socioeconomic data on outcomes. We retrospectively analyzed data from 165 patients who underwent surgery for spinal metastases between 2012-2023. The primary outcome was development of major complications (i.e., Clavien-Dindo Grade III-IV complications), and the secondary outcome was 30-day mortality (i.e., Clavien-Dindo Grade V complications). An exploratory data analysis that included sociodemographic, socioeconomic, clinical, oncologic, and operative parameters was performed. Following multivariable analysis, independent predictors of Clavien-Dindo Grade III-IV complications were Frankel Grade A-C, lower modified Bauer score, and lower Prognostic Nutritional Index. Independent predictors of Clavien-Dindo Grade V complications) were lung primary cancer, lower modified Bauer score, lower Prognostic Nutritional Index, and use of internal fixation. No sociodemographic or socioeconomic factor was associated with either outcome. Sociodemographic and socioeconomic factors did not impact short-term surgical outcomes for metastatic spinal tumor patients in this study. Optimization of modifiable factors like nutritional status may be more important in improving outcomes in this complex patient population.

The prognostic role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index on short- and long-term outcome following surgery for spinal metastases.

OBJECTIVE: Inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have shown promise in predicting mortality in various types of cancer. The purpose of this study was to assess NLR, PLR, and SII in predicting 30-day mortality and overall survival (OS) among surgically treated patients with spinal metastasis. METHODS: This was a retrospective study including 153 patients who underwent surgery for spinal metastasis between 2012 and 2022. Electronic medical records were manually reviewed, and NLR, PLR, and SII were calculated from preoperative neutrophil, platelet, and lymphocyte counts. Receiver operating characteristic curves with areas under the curve were generated to determine cutoff values. Logistic regression was used to determine the odds ratios (ORs) for 30-day mortality. The Kaplan-Meier method and Cox regression were used to determine the hazard ratio (HR) for OS limited to 5 years postoperatively. RESULTS: Preoperative cutoff values were as follows: NLR > 10.2, PLR > 260, and SII > 2900. Overall, 35.9% (55/153) of patients had elevated NLR, 45.7% (70/153) had elevated PLR, and 30.7% (47/153) had elevated SII. The overall 30-day mortality was 8.5% (13/153). After controlling for confounders such as performance status and primary tumor type, high NLR (OR 5.20, 95% CI 1.21-22.28; p = 0.026) and SII (OR 4.92, 95% CI 1.17-20.63; p = 0.029) were associated with increased odds of 30-day postoperative mortality. The median OS time in the study population was 26 months (95% CI 12-40 months). After controlling for confounders such as Eastern Cooperative Oncology Group status, primary tumor, and hypoalbuminemia, high NLR was associated with shorter OS (HR 2.23, 95% CI 1.48-3.97; p = 0.003). CONCLUSIONS: High preoperative NLR and SII were independently associated with 30-day postoperative mortality in this study. Elevated NLR was also found to be associated with shorter OS. The prognostic role of these metrics warrants further investigation.

The prognostic nutritional index (PNI) is independently associated with 90-day and 12-month mortality after metastatic spinal tumor surgery.

INTRODUCTION: Estimated postoperative survival is an important consideration during the decision-making process for patients with spinal metastases. Nutritional status has been associated with poor outcomes and limited survival in the general cancer population. The objective of this study was to evaluate the predictive utility of the prognostic nutritional index (PNI) for postoperative mortality after spinal metastasis surgery. METHODS: A total of 139 patients who underwent oncologic surgery for spinal metastases between April 2012 and August 2022 and had a minimum 90-day follow-up were included. PNI was calculated using preoperative serum albumin and total lymphocyte count, with PNI < 40 defined as low. The mean PNI of our cohort was 43 (standard deviation: 7.7). The primary endpoint was 90-day mortality, and the secondary endpoint was 12-month mortality. Multivariate logistic regression analyses were performed. RESULTS: The 90-day mortality was 27% (37/139), and the 12-month mortality was 56% (51/91). After controlling for age, ECOG performance status, total psoas muscle cross-sectional area (TPA), and primary cancer site, the PNI was associated with 90-day mortality [odds ratio 0.86 (95% confidence interval 0.79-0.94); p = 0.001]. After controlling for ECOG performance status and primary cancer site, the PNI was associated with 12-month mortality [OR 0.89 (95% CI 0.82-0.97); p = 0.008]. Patients with a low PNI had a 50% mortality rate at 90 days and an 84% mortality rate at 12 months. CONCLUSION: The PNI was independently associated with 90-day and 12-month mortality after metastatic spinal tumor surgery, independent of performance status, TPA, and primary cancer site.

Predictive value of six nutrition biomarkers in oncological spine surgery: a performance assessment for prediction of mortality and wound infection.

OBJECTIVE: Assessment of nutritional status is fundamental in cancer patients. The objective of this study was to assess the predictive ability of 6 nutritional biomarkers for postoperative mortality and wound infection after metastatic spinal tumor surgery. METHODS: A total of 139 patients who underwent oncological surgery for metastatic spine disease between April 2012 and August 2022 and had a minimum follow-up of 90 days were included. Six unique nutritional biomarkers were assessed: Prognostic Nutritional Index (PNI), Nutritional Risk Index (NRI), Controlling Nutritional Status Score (CONUT), total psoas cross-sectional area (TPA), body mass index (BMI), and body weight. Study endpoints were 90-day mortality rate, 12-month mortality rate, and wound infection. The discriminative ability of each of these markers was assessed with the c-statistic. A multivariate analysis was done for each of the biomarkers after a univariate analysis was first performed. RESULTS: The 90-day mortality rate was 27% (37 of 139). The biomarkers and respective c-statistics were as follows: PNI (0.74), NRI (0.75), CONUT (0.71), TPA (0.64), BMI (0.59), and body weight (0.60). The 12-month mortality rate was 56% (51 of 91). The biomarkers and respective c-statistics were as follows: PNI (0.72), NRI (0.73), CONUT (0.70), TPA (0.63), BMI (0.59), and body weight (0.60). The wound infection rate was 8% (11 of 139). The biomarkers and respective c-statistics were as follows: PNI (0.57), NRI (0.53), CONUT (0.55), TPA (0.57), BMI (0.48), and body weight (0.52). The PNI, NRI, and CONUT all predicted 90-day and 12-month mortality after multivariate regression analysis. No association between nutrition and wound infection was found. CONCLUSIONS: In this study, nutritional status was associated with postoperative mortality following oncological spine surgery. Three biomarkers predicted outcome independent of variables such as performance status or primary cancer. Future validation of these metrics is needed.

Evaluation of lymphopenia as a predictor of postoperative mortality and major complications in patients undergoing surgery for metastatic spine tumors.

OBJECTIVE: Lymphopenia is often seen in advanced metastatic disease and has been associated with poor postoperative outcomes. Limited research has been done to validate this metric in patients with spinal metastases. The objective of this study was to evaluate the capability of preoperative lymphopenia to predict 30-day mortality, overall survival (OS), and major complications in patients undergoing surgery for metastatic spine tumors. METHODS: A total of 153 patients who underwent surgery for metastatic spine tumor between 2012 and 2022 and met the inclusion criteria were examined. Electronic medical record chart review was conducted to obtain patient demographics, comorbidities, preoperative laboratory values, survival time, and postoperative complications. Preoperative lymphopenia was defined as < 1.0 K/µL based on the institution's laboratory cutoff value and within 30 days prior to surgery. The primary outcome was 30-day mortality. Secondary outcomes were OS up to 2 years and 30-day postoperative major complications. Outcomes were assessed with logistic regression. Survival analyses were done using the Kaplan-Meier method with log-rank test and Cox regression. Receiver operating characteristic curves were plotted to classify the predictive ability of lymphocyte count as a continuous variable on outcome measures. RESULTS: Lymphopenia was identified in 47% of patients (72 of 153). The overall 30-day mortality rate was 9% (13 of 153). In logistic regression analysis, lymphopenia was not associated with 30-day mortality (OR 1.35, 95% CI 0.43-4.21; p = 0.609). The mean OS in this sample was 15.6 months (95% CI 13.9-17.3 months), with no significant difference between patients with lymphopenia and those with no lymphopenia (p = 0.157). Cox regression analysis did not show an association between lymphopenia and survival (HR 1.44, 95% CI 0.87-2.39; p = 0.161). The major complication rate was 26% (39 of 153). In univariable logistic regression analysis, lymphopenia was not associated with the development of a major complication (OR 1.44, 95% CI 0.70-3.00; p = 0.326). Finally, receiver operating characteristic curves generated poor discrimination between lymphocyte count and all outcomes, including 30-day mortality (area under the curve 0.600, p = 0.232). CONCLUSIONS: This study does not support prior research that had shown an independent association between low preoperative lymphocyte level and poor postoperative outcomes following surgery for metastatic spine tumors. Although lymphopenia may be used to predict outcomes in other tumor-related surgeries, this metric may not hold a similar predictive capability in the population undergoing surgery for metastatic spine tumors. Further research into reliable prognostic tools is needed.

Performance Assessment of the American College of Surgeons Risk Calculator in Metastatic Spinal Tumor Surgery.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The objective of this study was to assess the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator performance in patients undergoing surgery for metastatic spine disease. SUMMARY OF BACKGROUND DATA: Patients with spinal metastases may require surgical intervention for cord compression or mechanical instability. The ACS-NSQIP calculator was developed to assist surgeons with estimating 30-day postoperative complications based on patient-specific risk factors and has been validated within several surgical patient populations. MATERIALS AND METHODS: We included 148 consecutive patients at our institution who underwent surgery for metastatic spine disease between 2012 and 2022. Our outcomes were 30-day mortality, 30-day major complications, and length of hospital stay (LOS). Predicted risk, determined by the calculator, was compared with observed outcomes using receiver operating characteristic curves with area under the curve (AUC) and Wilcoxon signed-rank tests. Analyses were repeated using individual corpectomy and laminectomy Current Procedural Terminology (CPT) codes to determine procedure-specific accuracy. RESULTS: Based on the ACS-NSQIP calculator, there was good discrimination between observed and predicted 30-day mortality incidence overall (AUC=0.749), as well as in corpectomy cases (AUC=0.745) and laminectomy cases (AUC=0.788). Poor 30-day major complication discrimination was seen in all procedural cohorts, including overall (AUC=0.570), corpectomy (AUC=0.555), and laminectomy (AUC=0.623). The overall median observed LOS was similar to predicted LOS (9 vs. 8.5 d, P =0.125). Observed and predicted LOS were also similar in corpectomy cases (8 vs. 9 d; P =0.937) but not in laminectomy cases (10 vs. 7 d, P =0.012). CONCLUSIONS: The ACS-NSQIP risk calculator was found to accurately predict 30-day postoperative mortality but not 30-day major complications. The calculator was also accurate in predicting LOS following corpectomy but not laminectomy. While this tool may be utilized to predict risk short-term mortality in this population, its clinical value for other outcomes is limited.

Performance assessment and external validation of specific thresholds of total psoas muscle cross-sectional area as predictors of mortality in oncologic spine surgery for spinal metastases.

PURPOSE: The purpose of this study was to assess the utility of low muscle mass (LMM) in predicting 90-day and 12-month mortality after spinal tumor surgery. METHODS: We identified 115 patients operated on for spinal metastases between April 2012 and August 2022 who had available perioperative abdominal or lumbar spine CT scans and minimum 90-day follow-up. LMM was defined as a total psoas muscle cross-sectional area (TPA) at the L4 pedicle level less than 10.5 cm2 for men and less than 7.2 cm2 for women based on previously reported thresholds. A secondary analysis was performed by analyzing TPA as a continuous variable. The primary endpoint was 90-day mortality, and the secondary endpoint was 12-month mortality. Multivariate logistic regression analyses were performed. RESULTS: The 90-day mortality was 19% for patients without and 42% for patients with LMM (p = 0.010). After multivariate analysis, LMM was not independently associated with increased odds of 90-day mortality (odds ratio 2.16 [95% confidence interval 0.62 to 7.50]; p = 0.223). The 12-month mortality was 45% for patients without and 71% for patients with LMM (p = 0.024). After multivariate analysis, LMM was not independently associated with increased odds of 12-month mortality (OR 1.64 [95% CI 0.46 to 5.86]; p = 0.442). The secondary analysis showed no independent association between TPA and 90-day or 12-month mortality. CONCLUSION: Patients with LMM had higher rates of 90-day and 12-month mortality in our study, but this was not independent of other parameters such as performance status, hypoalbuminemia, or primary cancer type.

Cochlear Implants: What the Neurosurgeon Needs to Know.

Patients with cochlear implants (CIs) commonly undergo neurosurgical interventions for concurrent pathologies. The neurosurgeon must be aware of the limitations these devices place on treating these patients and all pertinent interactions CIs have with common neurosurgical instruments and procedures. A literature search was performed utilizing the terms "cochlear implant" and "neurosurgery" or "neurosurgical" and all associated iterations. We reviewed the abstracts of 146 generated reports and eight published papers discussing the interaction and limitations of CI use in different neurosurgical procedures. Five realms were identified in which a CI may potentially interfere with standard neurosurgical care: Magnetic resonance imaging (MRI), radiotherapy, deep brain stimulation (DBS), intraventricular shunt placement, and intraoperative neuromonitoring (IONM). First, MRI use with CIs is limited due to thermal injury risk, imaging disruption, and implant damage. Secondly, high-dose >50 Gy single-fraction linear accelerator-based radiosurgery has been demonstrated to result in a loss of radio frequency link range in CIs, interfering with their function. Next, during surgery for DBS, the need for MRI and microelectrode recording requires CI magnet removal by neurotology and the surgeon must communicate with a non-hearing patient. Tunneling of shunts must accommodate CI position retroauricularly, if ipsilateral, and programmable valves must be placed >2 cm from the CI to prevent interference. Intraoperative neuromonitoring may produce voltages that interfere with CIs, and while monopolar cautery may pose the same risk, no study has proven this to date. Generally, bipolar cautery is safe and favored >1 cm from CIs. MRI use is limited in CI patients, although MRI-safer devices are in production. DBS electrodes may be successfully placed after CI magnet removal. Programmable shunt valves may be placed >2 cm away from CIs and radiosurgery <50 Gy has not demonstrated harm to these devices. IONM and monopolar cautery have not been demonstrated to directly affect CIs; however, more research is needed.

Cement Augmentation of Two-Level Lumbar Corpectomy Cage After Malposition: A Novel Salvage Procedure Technical Note.

Intervertebral cage mispositioning is an uncommon complication of a posterior lumbar corpectomy. Most frequently, cages are placed obliquely, laterally, or protruding. However, there are few reports of implanted cages that fail to contact the adjacent vertebral endplate and thus no descriptions of successful revisions. The objective of this case report is to report a unique case of minimally invasive rescue vertebroplasty with cement augmentation following a lumbar corpectomy that resulted in graft-endplate noncontact in a medically complicated patient A 60-year-old male with a history of active intravenous (IV) drug use, untreated hepatitis C virus (HCV) infection, and chronic malnourishment presented with low back pain. He had a history of vertebral osteomyelitis managed with intravenous antibiotics, although he was noncompliant with infusions. The diagnosis of L2-L3 discitis-osteomyelitis with intradiscal abscess causing cord compression was made using inpatient lumbar imaging. The initial intervention was accomplished with L2 and L3 vertebral corpectomy with decompression and expandable cage placement as well as a T10-pelvis posterior fixation. Despite the resolution of presenting symptoms, routine postoperative radiographs identified noncontact between the inferior surface of the cage and the superior endplate of the L4 vertebral body. Salvage therapy was pursued via fluoroscopy-guided vertebroplasty with cement augmentation to correct cage malposition. Secondary surgical intervention was successful in bringing the intervertebral cage into contact with the adjacent vertebral body. Lower extremity strength improved, and back pain was resolved. The postoperative motor examination remained unchanged after the rescue procedure. Accurate intraoperative cage placement can be difficult in patients with poor bone quality, especially in the setting of ongoing infection and cachexia. For this reason, routine postoperative imaging is crucial to assessing graft complications. In patients who are poor candidates for revision surgery, we demonstrate that an interventional radiology-based approach may be successful in correcting cage mispositioning and preventing further changes during healing and fusion.

An Artificial Neural Network Model for the Prediction of Perioperative Blood Transfusion in Adult Spinal Deformity Surgery.

Prediction of blood transfusion after adult spinal deformity (ASD) surgery can identify at-risk patients and potentially reduce its utilization and the complications associated with it. The use of artificial neural networks (ANNs) offers the potential for high predictive capability. A total of 1173 patients who underwent surgery for ASD were identified in the 2017-2019 NSQIP databases. The data were split into 70% training and 30% testing cohorts. Eighteen patient and operative variables were used. The outcome variable was receiving RBC transfusion intraoperatively or within 72 h after surgery. The model was assessed by its sensitivity, positive predictive value, F1-score, accuracy (ACC), and area under the curve (AUROC). Average patient age was 56 years and 63% were female. Pelvic fixation was performed in 21.3% of patients and three-column osteotomies in 19.5% of cases. The transfusion rate was 50.0% (586/1173 patients). The best model showed an overall ACC of 81% and 77% on the training and testing data, respectively. On the testing data, the sensitivity was 80%, the positive predictive value 76%, and the F1-score was 78%. The AUROC was 0.84. ANNs may allow the identification of at-risk patients, potentially decrease the risk of transfusion via strategic planning, and improve resource allocation.

Protective Effect of Portulaca oleracea Extract Against Lipopolysaccharide-Induced Neuroinflammation, Memory Decline, and Oxidative Stress in Mice: Potential Role of miR-146a and miR-let 7.

Neuroinflammation is an adaptive immune response to the central nervous system (CNS) injury induced by infection or toxins. MicroRNAs (miRs) showed critical roles in neuroinflammation as either proinflammatory or anti-inflammatory molecules. Interestingly, Portulaca oleracea (purslane) is an edible plant capable of ameliorating several diseases, including headache, burns, and diabetes; however, its effect on the neuroinflammation-associated miRs was not previously investigated. This study aimed to investigate the effect of aqueous purslane extract on the neuroinflammation induced by lipopolysaccharide (LPS) in mice and to identify its effect on animal cognition, oxidative stress, and expressions of miR-146a and miR-let 7. Adult mice were divided into the following groups: Normal group, LPS group, and Purslane+LPS group. Novel target recognition test, brain histopathology, and measurement of oxidative stress and inflammatory markers were performed. The results showed that LPS group exhibited significant decline in the cognitive memory, brain histopathological injury and a decrease in the number of intact neurons compared to the normal group. Furthermore, the LPS group showed a significant increase in malondialdehyde concentration, whereas superoxide dismutase and catalase activities were decreased. The LPS group also showed an increase in the inflammatory markers tumor necrosis factor-α and nuclear factor kappa B and downregulation of miR-146a and miR-let 7 expressions in the brain cells compared to the normal group, P value <.05. Interestingly, all these changes were reversed by administration of the aqueous purslane extract. In conclusion, the aqueous purslane extract protected from LPS-induced neuroinflammation and memory decline in mice through antioxidant and anti-inflammatory effect where upregulation of miR-146a and miR-1et 7 expressions was involved.

A Novel Clinical Scoring System for Perioperative Morbidity in Metastatic Spinal Tumor Surgery: The Spine Oncology Morbidity Assessment Score.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate a scoring system to predict morbidity for patients undergoing metastatic spinal tumor surgery (MSTS). SUMMARY OF BACKGROUND DATA: Multiple scoring systems exist to predict survival for patients with spinal metastasis. The potential benefits and risks of surgery need to be evaluated for patients with disseminated cancer and limited life expectancy. Few scoring systems exist to predict perioperative morbidity after MSTS. METHODS: We reviewed records of patients who underwent MSTS at our institution between 2013 and 2019. All perioperative complications occurring within 30 days were recorded. A clinical scoring system consisting of five variables (age ≥ 70 yr, hypoalbuminemia, poor preoperative functional status [Karnofsky ≤ 40], Frankel Grade A-C, and multilevel disease ≥2 continuous vertebral bodies) was evaluated as a predictive tool for morbidity; every parameter was assigned a value of 0 if absent or 1 if present (total possible score = 5). The effect of the scoring system on morbidity was evaluated using stepwise multiple logistic regression. Model accuracy was calculated by receiver operating characteristic analysis. RESULTS: One hundred and five patients were identified, with a male prevalence of 58.1% and average age at surgery of 61 years. The overall 30-day complication rate was 36.2%. The perioperative morbidity was 4.6%, 30.0%, 53.9%, and 64.7% for patients with scores of 0, 1, 2, and ≥3 points, respectively (P < 0.001). On multiple logistic regression analysis controlling for covariates not present in the model, the scoring system was significantly associated with 30-day morbidity (OR 3.11; 95% CI, 1.72-5.59; P < 0.001). The model's accuracy was estimated at 0.75. CONCLUSION: Our proposed model was found to accurately predict perioperative morbidity after MSTS. The Spine Oncology Morbidity Assessment (SOMA) score may prove useful for risk stratification and possibly decision-making, though further validation is needed.Level of Evidence: 4.

Potential Uses of Isolated Toxin Peptides in Neuropathic Pain Relief: A Literature Review.

Neuropathic pain is a subset of chronic pain that is caused by neurons that are damaged or firing aberrantly in the peripheral or central nervous systems. The treatment guidelines for neuropathic pain include antidepressants, calcium channel α2 delta ligands, topical therapy, and opioids as a second-line option. Pharmacotherapy has not been effective in the treatment of neuropathic pain except in the treatment of trigeminal neuralgia with carbamazepine. The inability to properly treat neuropathic pain causes frustration in both the patients and their treating physicians. Venoms, which are classically believed to be causes of pain and death, have peptide components that have been implicated in pain relief. Although some venoms are efficacious and have shown benefits in patients, their side-effect profile precludes their more widespread use. This review identifies and explores the use of venoms in neuropathic pain relief. This treatment can open doors to potential therapeutic targets. We believe that further research into the mechanisms of action of these receptors as well as their functions in nature will provide alternative therapies as well as a window into how they affect neuropathic pain.

Prognostic and predictive value of ERß1 and ERß2 in the Intergroup Exemestane Study (IES)-first results from PathIES†.

BACKGROUND: Intergroup Exemestane Study (IES) was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2-3 years from tamoxifen to exemestane. PathIES aimed to assess the potential prognostic and predictive value of ERß1 and ERß2 expression in primary tumours in order to determine benefit in the two treatment arms. PATIENTS AND METHODS: Primary tumour samples were available for 1256 patients (27% IES population). ERß1 and ERß2 expression was dichotomised at the median IHC score (high if ERß1 ≥ 191, ERß2 ≥ 164). Hazard ratios (HRs) were estimated by multivariable Cox proportional hazards models adjusting for clinicopathological factors. Treatment effects with biomarker expressions were determined by interaction tests. Analysis explored effects of markers both as a continuous variable and with dichotomised cut-offs. RESULTS: Neither ERß1 nor ERß2 were associated with disease-free survival (DFS) or overall survival (OS) in the whole cohort. In patients treated with continued tamoxifen, high ERß1 expression compared with low was associated with better DFS [HR = 0.38:95% confidence interval (CI) 0.21-0.68, P = 0.001]. DFS benefit of exemestane over tamoxifen (HR = 0.40:95% CI 0.22-0.70) was found in the low ERß1 subgroup (interaction P = 0.01). No significant difference with treatment was observed for ERß2 expression in either DFS or OS. CONCLUSION: In the PathIES population, exemestane appeared to be superior to tamoxifen among patients with low ERß1 expression but not in those with high ERß1 expression. This is the first trial of its kind to report a parameter potentially predicting benefit of an aromatase inhibitor when compared with tamoxifen and an independent validation is warranted.

NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer.

Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE100C or endocrine therapy: letrozole 2.5 mg, daily for 18-23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95% CI 57-81) were randomised. 12 (54.5, 95% CI 32.2-75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95% CI 36.4-79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2-4 and at surgery [fold change: 0.24 (95% CI 0.12-0.51) and 0.24; (95% CI 0.15-0.37), respectively]. Plasma total cfDNA levels rose from baseline to week 8 [fold change: chemotherapy 2.10 (95% CI 1.47-3.00), letrozole 1.47(95% CI 0.98-2.20)], and were maintained at surgery in the chemotherapy group [chemotherapy 2.63; 95% CI 1.56-4.41), letrozole 0.95 (95% CI 0.71-1.26)]. An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.

Role of diffusion-weighted MR imaging in cervical lymphadenopathy.

The role of diffusion-weighted magnetic resonance imaging (MRI) for differentiation between various causes of cervical lymphadenopathy was evaluated. In a prospective study, 31 untreated patients (22 males and nine females, aged 5-70 years) with 87 cervical lymph nodes underwent diffusion-weighted MRI before performance of neck dissection (n=14), surgical biopsy (n=9) or core biopsy (n=8). Diffusion-weighted MR images were acquired with a b factor of 0 and 1,000 s/mm2 using single-shot echo-planar sequence. Apparent diffusion coefficient (ADC) maps were reconstructed for all patients. The signal intensity of the lymph nodes was assessed on images obtained at b=0 or 1,000 s/mm2 and from the ADC maps. The ADC value of lymph nodes was also calculated. On the ADC map, malignant nodes showed either low (n=52) or mixed (n=20) signal intensity and benign nodes revealed high (n=13) or low (n=2) signal intensity. The mean ADC value of metastatic (1.09+/-0.11x10(-3) mm2/s) and lymphomatous (0.97+/-0.27x10(-3) mm2/s) lymph nodes was significantly lower than that of benign (1.64+/-0.16x10(-3) mm2/s) cervical lymph nodes (P<0.04). When an ADC value of 1.38x10(-3) mm2/s was used as a threshold value for differentiating malignant from benign lymph nodes, the best results were obtained with an accuracy of 96%, sensitivity of 98%, specificity of 88%, positive predictive value of 98.5% and negative predictive value of 83.7%. The smallest detected lymph node was 0.9 cm. In conclusion, diffusion-weighted MRI with ADC mapping is a new promising technique that can differentiate malignant from benign lymph nodes and delineate the solid viable part of the lymph node for biopsy. This technique provides additional useful physiological and functional information regarding characterization of cervical lymph nodes.

Technetium 99mTc-DTPA clearance in the evaluation of pulmonary involvement in patients with diabetes mellitus.

Systemic thickening of capillary endothelial basement membrane underlies the chronic complications of human diabetic microangiopathy. Since 99mTc-DTPA aerosol scintigraphy is a sensitive, non-invasive test of membrane permeability, we decided to study the effect of diabetes on the permeability of lung epithelium in diabetic patients using this test. Fifty (NIDDM) patients, aged 40-70 years, with or without complications, and who were non-smokers, were subjected to evaluation using 99mTc-DTPA aerosol. At the same time, pulmonary function tests, including carbon monoxide diffusion capacity, were done. Normal non-smoking subjects with no history of cardio-respiratory disease, who underwent 99mTc-DTPA and pulmonary function tests, served as controls. The risk factors which included age, sex, degree of control and presence of complications were noted. Twenty-nine (58%) of the patients had abnormal 99mTc-DTPA clearance. Thirty-four percent of the patients with complications and 24% of those without complications had abnormal clearance. Complications recorded included retinopathy, neuropathy and nephropathy. Fifty-five percent of patients with abnormal 99mTc-DTPA had suffered from diabetes for longer than 10 years. Sixty-two percent of patients with poor glycaemic control had abnormal 99mTc-DTPA. Diffusion capacity was not significantly affected in patients with complicated diabetes. Our preliminary results suggest that 99mTc-DTPA is a potentially sensitive test in assessing the degree of lung affection in diabetic patients. No significant correlation exists between diffusion capacity and 99mTc-DTPA. The risk factors did not affect the 99mTc-DTPA clearance, probably due to the small sample size.