Control of proton transport and hydrogenation in double-gated graphene.

The basal plane of graphene can function as a selective barrier that is permeable to protons1,2 but impermeable to all ions3,4 and gases5,6, stimulating its use in applications such as membranes1,2,7,8, catalysis9,10 and isotope separation11,12. Protons can chemically adsorb on graphene and hydrogenate it13,14, inducing a conductor-insulator transition that has been explored intensively in graphene electronic devices13-17. However, both processes face energy barriers1,12,18 and various strategies have been proposed to accelerate proton transport, for example by introducing vacancies4,7,8, incorporating catalytic metals1,19 or chemically functionalizing the lattice18,20. But these techniques can compromise other properties, such as ion selectivity21,22 or mechanical stability23. Here we show that independent control of the electric field, E, at around 1 V nm-1, and charge-carrier density, n, at around 1 × 1014 cm-2, in double-gated graphene allows the decoupling of proton transport from lattice hydrogenation and can thereby accelerate proton transport such that it approaches the limiting electrolyte current for our devices. Proton transport and hydrogenation can be driven selectively with precision and robustness, enabling proton-based logic and memory graphene devices that have on-off ratios spanning orders of magnitude. Our results show that field effects can accelerate and decouple electrochemical processes in double-gated 2D crystals and demonstrate the possibility of mapping such processes as a function of E and n, which is a new technique for the study of 2D electrode-electrolyte interfaces.

From morbidity reduction to cost-effectiveness: Enhanced recovery after surgery (ERAS) society recommendations in minimal invasive liver surgery.

PURPOSE: Minimal-invasive liver surgery (MILS) reduces surgical trauma and is associated with fewer postoperative complications. To amplify these benefits, perioperative multimodal concepts like Enhanced Recovery after Surgery (ERAS), can play a crucial role. We aimed to evaluate the cost-effectiveness for MILS in an ERAS program, considering the necessary additional workforce and associated expenses. METHODS: A prospective observational study comparing surgical approach in patients within an ERAS program compared to standard care from 2018-2022 at the Charité - Universitätsmedizin Berlin. Cost data were provided by the medical controlling office. ERAS items were applied according to the ERAS society recommendations. RESULTS: 537 patients underwent liver surgery (46% laparoscopic, 26% robotic assisted, 28% open surgery) and 487 were managed by the ERAS protocol. Implementation of ERAS reduced overall postoperative complications in the MILS group (18% vs. 32%, p = 0.048). Complications greater than Clavien-Dindo grade II incurred the highest costs (€ 31,093) compared to minor (€ 17,510) and no complications (€13,893; p < 0.001). In the event of major complications, profit margins were reduced by a median of € 6,640. CONCLUSIONS: Embracing the ERAS society recommendations in liver surgery leads to a significant reduction of complications. This outcome justifies the higher cost associated with a well-structured ERAS protocol, as it effectively offsets the expenses of complications.

Graduate Student Literature Review: The use of integrated sensor data for the detection of hyperketonemia in pasture-based dairy systems during the transition period.

This review evaluates research regarding the use of sensors to predict and manage hyperketonemia (HYK) in dairy cows during the transition period, with a focus on pasture-based systems. By doing so, we assessed the accuracy of HYK detection models, noting that no studies thus far have produced models with sufficient accuracy for practical use. Sensors have been validated for their use in dairy farming, proving they produce reliable and useful information. Research is beginning to focus on the analysis of multiple sensors together as a sensor system, discovering the potential for these technologies to be a valuable aid in decision making and farm management. Of the studies that use sensors to predict and manage disease in dairy cows, few studies use data integration (the process of combining data from multiple sensors which in turn improves model accuracy), highlighting a gap in the literature. Recently published research has focused on the detection of mastitis and lameness in pasture-based systems, with less focus toward the detection of metabolic disease. This is reflected in the lack of studies that report the prevalence of metabolic diseases, such as HYK, in pasture-based systems, especially in Australia and New Zealand. It is suggested that further research focuses on (1) determining the prevalence and impact of HYK in pasture-based systems; (2) exploring the use of sensors for HYK detection in pasture-based systems; (3) improving model accuracy with data integration; and (4) confirming the economic benefit of sensors to justify the cost of investing in sensor systems.

Management of treatment-related sequelae following colorectal cancer.

AIM: Colorectal cancer survivors are one of the most rapidly growing groups of patients living with and beyond cancer. In a national multidisciplinary setting, we have examined the extent of late treatment-related sequelae in colorectal cancer survivors and present the scientific evidence for management of these conditions in this patient category with the aim of facilitating identification and treatment. METHOD: A systematic search for existing guidelines and relevant studies was performed across 16 and 4 databases, respectively, from inception to 2021. This yielded 13 guidelines and 886 abstracts, of which 188 were included in the finalized guideline (231 included for full text review). Secondarily, bibliographies were cross-referenced and 53 additional articles were included. RESULTS: Symptoms have been divided into overall categories including psychosocial, bowel-related, urinary, sexual (male and female), pain/neuropathy and fatigue symptoms or complaints that are examined individually. Merging and grading of data resulted in 22 recommendations and 42 management strategies across categories. Recommendations are of a more general character, whereas management strategies provide more practical advice suited for initiation on site before referral to specialized units. CONCLUSION: Treatment-related sequelae in colorectal cancer survivors are common and attention needs to be focused on identifying patients with unmet treatment needs and the development of evidence-based treatment algorithms.

Assessment of caesarean section and inguinal hernia repair as proxy indicators of total number of surgeries.

BACKGROUND: The traditional instruments used to assess surgical capacity in low-income countries require substantial amounts of time and resources, and have thus not been systematically used in this context. Proxy indicators have been suggested as a simpler method to estimate surgical volume. The aim of this study was to assess caesarean section and inguinal hernia repair as proxy indicators of the total number of surgeries performed per capita in a given region in Sierra Leone in sub-Saharan Africa. METHODS: Avaliable handwritten surgical data were compiled from 58 (96·7%) health institutions that performed WHO defined major surgery in Sierra Leone in 2012 (from Jan 1, to Dec 31). 24 152 surgical procedures were included in the study. Validity of proxy indicators was tested by logistic regression analyses with the rate of caesarean sections compared with total operations (% CS), hernia repairs (% HR), or both (% CS plus HR) as dependent variables and the operations per 100 000 capita as the covariate. FINDINGS: The number of operations per 100 000 capita for the 13 districts of Sierra Leone varied from 909 in the urban Western District to 32 in the rural district of Moyamba. There was a significant negative correlation between each of the proxy indicators and the number of operations per 100 000 capita. For changes in the operations per 100 000 capita of 100, we obtained an estimated odds ratio for the % CS proxy indicator of 0·675 (95% CI 0·520-0·876; p<0·01), % HR being 0·822 (0·688-0·983; p<0·05), and for % CS plus HR being 0·838 (0·731-0·962; p<0·05). INTERPRETATION: The unmet need for surgical services in Sierra Leone can be estimated by either of the three proxy indicators. However, it seems that % CS is more sensitive to small changes in operations per 100 000 capita compared with the % HR. There is no obvious added benefit of use of the combined proxy indicator. Although this study shows that proxy indicators are a promising method to evaluate surgical activity, this is a cross-sectional study and can thus only show correlation. Longitudinal studies would strengthen these findings. FUNDING: Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway, and CapaCare.

Reply to Soldo, A.; Lipej, L. Comment on "Balàka et al. Updated Checklist of Chondrichthyan Species in Croatia (Central Mediterranean Sea). Biology 2023, 12, 952".

Balàka et al [...].

Circulating long noncoding RNA PDE4DIPP6: A novel biomarker for improving the clinical management of non-ST-segment elevation myocardial infarction.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers. Here, we investigated the cardiac-expressed and plasma-detectable lncRNA PDE4DIPP6 as a biomarker for non-ST-segment elevation myocardial infarction (NSTEMI), specifically assessing its potential to enhance the diagnostic efficacy of high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS: The study enrolled individuals presenting with suspected acute coronary syndrome (ACS). LncRNA quantification was performed in plasma samples using RT-qPCR. The discriminatory performance was assessed by calculating the Area Under the Curve (AUC). Reclassification metrics, including the Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) indexes, were utilized to evaluate enhancements in diagnostic accuracy. Among the 252 patients with suspected ACS, 50.8 % were diagnosed with ACS, and 13.9 % with NSTEMI. Initially, the association of lncRNA PDE4DIPP6 with ACS was investigated. Elevated levels of this lncRNA were observed in ACS patients compared to non-ACS subjects. No association was found between lncRNA PDE4DIPP6 levels and potential confounding factors, nor was a significant correlation with hs-cTnT levels (rho = 0.071). The inclusion of lncRNA PDE4DIPP6 on top of hs-cTnT significantly improved the discrimination and classification of ACS patients, as reflected by an enhanced AUC of 0.734, an IDI of 0.066 and NRI of 0.471. Subsequently, the lncRNA PDE4DIPP6 was evaluated as biomarker of NSTEMI. Elevated levels of the lncRNA were observed in NSTEMI patients compared to patients without NSTEMI. Consistent with previous findings, the addition of lncRNA PDE4DIPP6 to hs-cTnT improved the discrimination and classification of patients, increasing the AUC from 0.859 to 0.944, with an IDI of 0.237 and NRI of 0.658. CONCLUSION: LncRNA PDE4DIPP6 offers additional diagnostic insights beyond hs-cTnT, suggesting its potential to improve the clinical management of patients with NSTEMI.

miRNA as potential biomarkers after liver transplantation: A systematic review.

BACKGROUND: Liver transplantation is a life-saving therapy for end-stage liver disease patients, but acute cellular rejection (ACR) and graft complications remain significant postoperative challenges. Early and accurate diagnosis is crucial for timely intervention and improved patient outcomes, but their diagnosis rely currently on invasive biopsy sampling, thus prompting the search for non-invasive Biomarkers. MicroRNA (miRNA) have emerged as promising biomarkers in various pathological conditions, and their potential utility in diagnosing acute cellular rejection after liver transplantation has gained significant interest. METHODS: This systematic review of PubMed, Web of Science, and the ClinicalTrials.gov registry analyzes studies exploring miRNA as biomarkers for ACR and graft dysfunction in liver transplantation (PROSPERO ID CRD42023465278). The Cochrane Collaboration tool for assessing risk of bias was employed. Population data, identified miRNA and their dynamic regulation, as well as event prediction were compared. Data extraction and quality assessment were performed independently by two reviewers. RESULTS: Thirteen studies were included in this systematic review. Various investigated miRNAs were upregulated in association with acute cellular rejection, like miR-122, miR-155, miR-181, miR-483-3p, and miR-885-5p, demonstrating great biomarker potential. Additionally, several studies conducted target gene analysis, revealing insights into cellular mechanisms linked to ACR. Moreover, various miRNA were also capable of predicting different organ complications following transplantation, expanding their versatility. Remaining challenges include the standardization of miRNA profiling, the need for functional validation, and the necessity for long-term studies. CONCLUSION: The results highlight the potential of miRNA as specific, non-invasive biomarkers for ACR and graft dysfunction following liver transplantation. However, further research is needed to validate these findings and establish standardized diagnostic panels to incorporate them into clinical practice and explore miRNA-based therapies in the future.

Dysphagia after definitive radiotherapy for head and neck cancer. Correlation of dose-volume parameters of the pharyngeal constrictor muscles.

BACKGROUND: Dysphagia is a complication of head and neck cancer patients undergoing radiotherapy (RT). We analysed frequency and severity of swallowing dysfunction and correlated these findings with dose-volume histograms (DVHs) of the pharyngeal constrictor muscles. METHODS: A total of 50 patients treated by radical RT were enrolled. DVHs of constrictor muscles were correlated with acute and late dysphagia and with the items of three quality of life questionnaires. RESULTS: Mean dose to superior and middle constrictor muscles (SCM, MCM), partial volume of SCM and MCM receiving a dose ≥ 50 Gy dose to the whole constrictor muscles ≥ 60 Gy and tumour location were associated to late dysphagia at univariate analysis. Mean dose to the MCM was the only statistically significant predictor of late dysphagia at the multivariable analysis. CONCLUSION: The study shows a significant relationship between long-term dysphagia and mean doses to SCM, MCM, whole constrictor muscles, and oropharyngeal tumour. This finding suggests a potential advantage in reducing the RT dose to swallowing structures to avoid severe dysphagia.

[Validation of BR23 questionnaire for the assessment of quality of life of breast cancer patients in Chile]. / Calidad de vida en cáncer de mama: validación del cuestionario BR23 en Chile.

BACKGROUND: Quality of Life assessment in oncologic patients evaluates the impact and sequels of the disease ana the adverse effects of available treatments. AIM: To validate in Chile the breast cancer specific-questionnaire (BR23) developed by the European Organization for Research and Treatment of Cancer (EORTC). PATIENTS AND METHODS: After performing a linguistic validation of the BR23 according to EORTC instructions, its psychometric properties were tested in 103 patients with breast cancer whose ages ranged from 34 to 83 years. Internal consistency of the scales was assessed using the Cronbach's alpha coefficient. The test-retest correlations of each scale (n = 83) were evaluated. The correlation of BR23 scales with SF36 version 2 and C30 version 3.0 scales was also assessed. The sensitivity and specificity of the instrument were analyzed using receiver operating characteristic curves (ROC). RESULTS: Alpha values showed acceptable levels of internal consistency, ranging between 0.702 and 0.917 in all scales of BR23. The statistical analysis revealed significant test-retest correlations in most scales of BR23. The correlations between BR23 and similar domains of C30 and SF36 questionnaires were also significant. The BR23 questionnaire demonstrated satisfactory levels of sensitivity and specificity when compared with the SF-36 scale. CONCLUSIONS: The BR23 questionnaire adapted for use in Chile is linguistically appropriate and psychometrically valid.

Updated Checklist of Chondrichthyan Species in Croatia (Central Mediterranean Sea).

Almost half of all chondrichthyan species in the Mediterranean Sea are threatened with extinction, according to the IUCN Red List. Due to a substantial lack of access to data on chondrichthyan catches in the Mediterranean Sea, especially of threatened species, the implementation of conservation measures is extremely insufficient. This also concerns the Adriatic Sea. Here we present a detailed and up-to-date assessment of the species occurring in Croatian waters, as the last checklist of chondrichthyans in Croatian waters was conducted in 2009. Occurrence records from historical data, literature and citizen science information have been compiled in order to present a comprehensive list of species occurrences. We found 54 chondrichthyan species between 1822 and 2022, consisting of a single chimaera, 23 rays and skates, and 30 shark species. Here, four additional species are listed but are considered doubtful. Five species are reported here for the first time for Croatian waters that were not listed in the survey from 2009. Nearly one-third of the species reported here are critically endangered in the entire Mediterranean Sea, based on the IUCN Red List. Additionally, we revisited the Croatian records of the sandtiger shark Carcharias taurus Rafinesque, 1810 and discussed its potential confusion with the smalltooth sandtiger shark Odontaspis ferox (Risso, 1810). Our results thus provide novel insights into the historical and current distribution patterns of chondrichthyan fishes in the Croatian Sea and provide a basis for further research as well as conservation measures.

Artificial intelligence can detect left ventricular dilatation on contrast-enhanced thoracic computer tomography relative to cardiac magnetic resonance imaging.

OBJECTIVES: To assess the diagnostic accuracy of an automated algorithm to detect left ventricular (LV) dilatation on non-ECG gated CT, using cardiac magnetic resonance (CMR) as reference standard. METHODS: Consecutive patients with contrast-enhanced CT thorax and CMR within 31 days (2016-2020) were analysed (n = 84). LV dilatation was defined against age-, sex- and body surface area-specific values for CMR. CTs underwent automated artificial intelligence(AI)-derived analysis that segmented ventricular chambers, presenting maximal LV diameter and volume. Area under the receiver operator curve (AUC-ROC) analysis identified CT thresholds with ≥90% sensitivity and highest specificity and ≥90% specificity with highest sensitivity. Youden's Index was used to identify thresholds with optimised sensitivity and specificity. RESULTS: Automated diameter analysis was feasible in 92% of cases (77/84; 45 men, age 61 ± 14 years, mean CT to CMR interval 10 ± 8 days). Relative to CMR as a reference standard, 45% had LV dilatation. In males, an automated LV diameter measurement of ≥55.5 mm was ≥90% specific for CMR-defined LV dilatation (positive predictive value (PPV) 85.7%, negative predictive value (NPV) 61.2%, accuracy 68.9%). In females, an LV diameter of ≥49.7 mm was ≥90% specific for CMR-defined LV dilatation (PPV 66.7%, NPV 73.1%, accuracy 71.9%). AI CT volumetry data did not significantly improve AUC performance. CONCLUSION: Fully automated AI-derived analysis LV dilatation on routine unselected non-gated contrast-enhanced CT thorax studies is feasible. We have defined thresholds for the detection of LV dilatation on CT relative to CMR, which could be used to routinely screen for dilated cardiomyopathy at the time of CT. ADVANCES IN KNOWLEDGE: We show, for the first time, that a fully-automated AI-derived analysis of maximal LV chamber axial diameter on non-ECG-gated thoracic CT is feasible in unselected real-world cases and that the derived measures can predict LV dilatation relative to cardiac magnetic resonance imaging, the non-invasive reference standard for determining cardiac chamber size. We have derived sex-specific cut-off values to screen for LV dilatation on routine contrast-enhanced thoracic CT. Future work should validate these thresholds and determine if technology can alter clinical outcomes in a cost-effective manner.

Subacute combined degeneration of the cord secondary to nitrous oxide misuse: No laughing matter.

Nitrous oxide (N2O) has several traditional uses as a surgical and dental anaesthetic, as well as in aerosol spray propellants. It is the combination of analgesic and euphoric qualities coupled with accessibility as an over-the-counter household item that lends N2O to recreational use. Despite increasing evidence that prolonged use of N2O both medically and as a drug of abuse can cause disabling neurological side-effects, it remains widely used. We present the case of an 18-year-old male who was diagnosed with subacute combined degeneration of the cord (SCDC) secondary to acute, heavy recreational use of N2O. The patient presented with progressive paraesthesia affecting his hands and feet associated with distal weakness. MRI of the cervical spine revealed symmetric bilateral high T2 signal within the dorsal columns extending from the level of C2 to T2 with the inverted 'V' sign on axial T 2-weighted slices indicative of SCDC. Although vitamin B12 levels were within normal range, marked elevation of methylmalonic acid and homocysteine support the diagnosis of B12 inactivation and functional B12 deficiency, which fully resolved with treatment.

18FDG-PET/CT findings in COVID-19: a single centre retrospective radiological review.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the infectious disease COVID-19, was declared a global pandemic in March 2020. As radiology departments recommence 18FDG-PET/CT imaging, it is likely that both asymptomatic and specific symptomatic patients with COVID-19 infection will be imaged, particularly if the disease becomes endemic in the UK. We review the clinical scenarios where 18FDG-PET/CT could be performed in COVID-19 positive patients. Our local protocol for safely scanning known COVID-19 positive patients is described, highlighting considerations for other departments. We present the findings from a series of known COVID-19 positive patients and two further asymptomatic cases evaluated with18FDG-PET/CT. Classic, indeterminate, normal and non-COVID-19 manifestations on both the 18FDG-PETand low dose CT component are described as an aid for radiologists and nuclear medicine physicians when reporting 18FDG PET/CT.

Chondrosarcoma of the larynx: a case report.

Chondrosarcomas of the larynx are rare cancers and are more frequently located at cricoid cartilage level. They are characterised by a low tendency to metastatic diffusion (low grade). The treatment of choice is surgery, which may be endoscopic or "open partial surgery", if extension of the cancer is limited. Prognosis is generally good. In this report, a case of low malignancy chondrosarcoma of the larynx is presented, which was treated surgically with a glottic-hypoglottic laryngectomy according to Serafini-Bartual. Chondrosarcoma of the larynx shows a slow and painless growth, the first symptom is often an ingravescent dysphonia. Laryngoscopy reveals tumefaction of the larynx, covered by intact mucosa. Computerized tomography imaging with contrast and magnetic resonance imaging defines not only coarse calcifications, pathognomonic of chondromatous neo-formations but also the relationship of the neoformation with the surrounding tissues. However, histology remains the gold standard for diagnostic purposes. Treatment is essentially surgical; it must allow eradication of the cancer between specific safety margins and, it must, at the same time, be functional, if the lesion does not extend beyond half of the cricoid circle and if histological grade is low.

Impact of resection margin status on oncological outcomes after CO2 laser cordectomy.

The management of positive resection margins in micro-endoscopic glottic laser surgery remains a controversial and critical point. This study aims to assess the impact of margin status after transoral laser surgery on local control, survival and organ preservation rates; the decision-making process and treatment options in cases with positive margins are also discussed. We retrospectively reviewed the clinical and histological records of 308 consecutive patients with primary early glottic carcinoma (T1a, T1b, selected T2) and treated with endoscopic laser cordectomy. Recurrence rates and survival related to margin status were analysed using the Kaplan-Meier method. Local relapses and disease-free-survival rates were significantly related to excision margin status (p < 0.001). In the T1a category (n = 228) no significant differences were observed in disease-free-survival (p = 0.889) and overall survival (p = 0.426) between patients submitted to further treatment (revision endoscopic surgery or radiotherapy) for positive excision margins and patients who were left untreated. In 20 of 24 (83%) patients with positive margins that were surgically re-excised, no residual carcinoma was detected. Margin status (mainly multifocal and deep positive margins) at first surgery was significantly related to the final organ preservation rate (p < 0.001). Margin status during laser cordectomy in early glottic cancer has a prognostic impact on local control of disease without compromising survival. Patients with multifocal and deep positive borders should be surgically retreated and strictly monitored to increase the organ preservation rates. Careful preparation and mapping of the surgical specimen enhances the accuracy of pathological examination by reducing the risk of overestimate positive margins.

[Cutaneous spreading of a chordoma]. / Extension cutanée d'un chordome.

INTRODUCTION: Chordomas are rare extradural bone tumors arising from notochord remnants, the embryonic structure forming the original axis of the spine. They represent 0.1p. 100 of all intra-cranial tumors. The chordoma is a locally malignant cancer that tends to invade the surrounding tissues. Its localization in the skin is exceptional. OBSERVATION: A 56 year-old man developed a nut-sized vegetating nodule on the nasal groove. This lesion appeared a few months following surgery for a frontoglabellar relapse of a chordoma that had developed six years earlier at the base of the skull. DISCUSSION: We report this case because of the rareness of cutaneous involvement and the particular conditions in which it occurred. It may have been due to tumoral seeding during the previous surgical interventions.

P53 overexpression correlates with proliferative activity and prognosis in carcinomas of the pyriform sinus.

p53 overexpression and proliferative activity were investigated in 28 squamous cell carcinomas of the pyriform sinus of the hypopharynx prior to therapy, using DO1 and MIB-1 monoclonal antibodies in routinely processed biopsies. MIB-1 scores were associated with tumour histological grade (35.4% for grade 3 versus 23.8% for grade 2 cases; p=0.008) and survival (the median of survival was 23 months for cases with MIB-1 scores less than or equal to 33.8% but 11 months only for cases with MIB-1 scores >33.8%; p<0.001). p53 scores were associated with tumour histological grade (56.5% for grade 3 versus 37.1% for grade 2 cases; p=0.02) and survival (median of survival 20 months for cases with p53 scores less than or equal to 56.2% versus 11 months for cases with p53 scores >56.2%; p=0.002). Tumour histological grade was also correlated with prognosis (median of survival 50 months for grade 2 versus 14 months for grade 3 cases; p=0.03). In the multivariate analysis, only MIB-1 (p=0.001) and p53 scores (p=0.003) had an independent prognostic significance. A linear relationship between p53 and MIB-1 scores was observed (r=0.54; p=0.012). With the limitation due to the small number of cases, our findings indicate that p53 overexpression correlates with proliferative activity and survival in squamous cell carcinomas of the pyriform sinus, and suggest the use of p53 and MIB-1 immunostainings in the pretherapeutic assessment of the tumour aggressiveness.

Argyrophilic nucleolar organizer region counts and proliferating cell nuclear antigen scores are two reliable indicators of survival in pharyngeal carcinoma.

The proliferative activity of pharyngeal carcinoma has been investigated by means of monoclonal antibody PC10 against proliferating cell nuclear antigen (PCNA/cyclin) and argyrophilic nucleolar organizer region (AgNOR) analysis in formalin-fixed, paraffin-embedded biopsies from 45 primary squamous and undifferentiated carcinomas, prior to therapy. The correlation between AgNOR counts and PCNA(PC10) scores was highly significant (r = 0.73; P < 0.0001) as determined by Pearson's correlation coefficient. Moreover, the univariate Kaplan-Meier survival analysis showed a significant correlation between 3- and 5-year survival rates and the mean AgNOR number per tumour cell (P = 0.0003) or the percentage of PCNA(PC10)-positive cells (P = 0.0001). Our results indicate that both AgNOR counts and PCNA(PC10) scores are reliable markers of the proliferative activity of pharyngeal carcinoma in small, routinely processed biopsies, in which they can allow simultaneous evaluation of the histology and tumour cell kinetics.

Postoperative enteral immunonutrition in head and neck cancer patients.

AIMS: to determine if postoperative feeding of head and neck cancer patients, using an enteral diet supplemented with arginine, improves immunological and nutritional status, and clinical outcome, i.e., reduces postoperative infectious/wound complications and length of stay, when compared with an isocaloric, isonitrogenous control diet. METHODS: at operation 44 patients were randomized into two groups to receive: a) an enriched diet (n=23);b) an isocaloric, isonitrogenous control diet (n=21). Thirteen patients with a history of significant weight loss (> or = 10% over the last 6 months) were considered malnourished. Preoperatively and on postoperative days 1, 4 and 8 the following parameters were evaluated: albumin, prealbumin, transferrin, total number of lymphocytes, lymphocyte subsets (CD3, CD4, CD8 and CD4/CD8 ratio) and immunoglobulins. Postoperative complications and length of stay were recorded. RESULTS: 'visceral' serum proteins and immunological parameters decreased on postoperative day 1 in both groups. However, only the enriched group demonstrated a significant increase (P<0.05) in the total number of lymphocytes, CD4, CD4/CD8 on postoperative day 4, and total number of lymphocytes, CD3, CD4, CD4/CD8 on postoperative day 8. In the malnourished subgroup the administration of the enriched formula significantly reduced both postoperative infectious/wound complications and length of stay compared with the control group (P<0.05). CONCLUSIONS: enteral immunonutrition of head and neck cancer patients improves postoperative immunological response. Significant clinical advantages were observed in malnourished patients.