Outpatient surgery of the first ray of the foot: post-operative pain monitoring at home.

INTRODUCTION: At present, health facilities are forced to switch to outpatient care. While it lends itself well to this organizational arrangement, first ray surgery is broadly considered as painful by patients, who are often reluctant to this treatment. The evolution of post-operative pain in patients who underwent operations for first ray surgery from D0 to D15 were studied. Secondly, the duration of the oral analgesic treatment, the patient's satisfaction level, and searched for complications were assessed. METHODS: This is an observational, single-center and single-operator study. Between July and December 2019, forty patients who underwent first ray surgery (hallux valgus or rigidus) and eligible for outpatient treatment were included. The surgical technique of the hallux valgus treatment consisted of open surgery via double metatarsal and phalangeal osteotomy. The hallux rigidus surgery consisted of arthrodesis using an open dorsal plate. Home monitoring was carried out by a healthcare provider (e-HORUS). The protocol provided for pain management by means of a diffuser of Nefopam IV for a maximum of 5 days, combined with alleviating oral analgesics 1 and 2 and NSAIDs. The pain was evaluated on D0, D1, D3, D5, D8 and D15, using a numerical scale (NS) from 0 to 10. The degree of patient satisfaction was recorded at 1 month. RESULTS: 35 patients were followed. 5 patients were excluded due to incomplete data. The series included 26 women and 9 men, with an average age of 59.9 years. There were 30 hallux valgus and 5 hallux rigidus. The pain analyzed by the NS was 5.37 on D0, 3.34 on D1, 1.83 on D3, 1.43 on D5, 1.06 on D8 and 2.2 on D15. The average duration of Nefopam infusions was 3.89 days, and the average duration of oral analgesics was 17.7 days. The tolerance of the treatment was satisfactory in 79% of the cases. 69% of patients were very satisfied with the management of their pain. There were no scar complications or infections. No re-hospitalization was necessary. 3 algoneurodystrophies were identified. The existence of fibromyalgia or Parkinsonian syndrome was correlated with higher pain. DISCUSSION-CONCLUSION: Pain management after outpatient first ray surgery using the injectable Nefopam protocol was satisfactory in the majority of cases, with a high degree of patient satisfaction. This protocol is routinely offered to our patients who must undergo first ray surgery.

Effects of serum deprivation on the mechanical properties of adherent vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) function plays a key role in regulating the development and progression of vascular lesions. Among the more significant phenomena that occur during the development of these lesions is the phenotypic switching of VSMCs from a contractile to a synthetic state. A better understanding of the concurrent changes to VSMC mechanical properties that occur with phenotypic shifts can help to elucidate the role of VSMC mechanics in the development of vascular diseases. In the current study, the mechanical properties of adherent cultured rat aortic VSMCs were assessed by atomic force microscopy. Serum starvation was used to induce a phenotypic shift in vitro. It was concluded that serum starvation led to a statistically significant increase in apparent elastic modulus after 5 days, as well as a statistically significant decrease in hysteresis after culture for 3 days. If this trend of VSMC mechanical properties changing concurrently with phenotypic shifts were to hold true in vivo, such changes could affect the processes of mechanotransduction and/or arterial mechanical properties, thereby contributing to the progression of vascular disease.

DairyWise, a whole-farm dairy model.

A whole-farm dairy model was developed and evaluated. The DairyWise model is an empirical model that simulated technical, environmental, and financial processes on a dairy farm. The central component is the FeedSupply model that balanced the herd requirements, as generated by the DairyHerd model, and the supply of homegrown feeds, as generated by the crop models for grassland and corn silage. The output of the FeedSupply model was used as input for several technical, environmental, and economic submodels. The submodels simulated a range of farm aspects such as nitrogen and phosphorus cycling, nitrate leaching, ammonia emissions, greenhouse gas emissions, energy use, and a financial farm budget. The final output was a farm plan describing all material and nutrient flows and the consequences on the environment and economy. Evaluation of DairyWise was performed with 2 data sets consisting of 29 dairy farms. The evaluation showed that DairyWise was able to simulate gross margin, concentrate intake, nitrogen surplus, nitrate concentration in ground water, and crop yields. The variance accounted for ranged from 37 to 84%, and the mean differences between modeled and observed values varied between -5 to +3% per set of farms. We conclude that DairyWise is a powerful tool for integrated scenario development and evaluation for scientists, policy makers, extension workers, teachers and farmers.

Flow cytometric S-phase fraction contributes to diagnosis of diploid malignant salivary gland tumours.

DNA ploidy studies on salivary gland tumours have shown that the proportion of aneuploid cases, although confined to the malignant entities, is considerably lower than for other solid malignancies. To analyse whether the S-phase fraction (SPF) may contribute to discrimination of diploid malignant from benign tumours, DNA flow cytometric data from 45 different malignant salivary gland tumours was compared with that of 121 pleomorphic adenomas. All benign tumours were diploid. Twelve malignant tumours contained aneuploid cell populations. The SPF values for diploid malignancies ranged between 0.9% and 11.0% (mean 3.9%), and between 0.5% and 7.9% (mean 2.7%) for pleomorphic adenomas. A 4% cut-off value gained statistical significance for discriminating diploid malignant tumours from pleomorphic adenomas (P<0.01). The sensitivity for SPF>4% was 46% and the positive predictive value was 40%. A sensitivity of 60% and a positive predictive value of 54% was achieved by combining aneuploidy and SPF>4%. These results show that DNA flow cytometry may contribute to diagnostic assessment in salivary gland tumours.

Fibromyalgia and Gaucher's disease.

BACKGROUND: Patients with symptomatic Gaucher's disease sometimes have non-specific symptoms (such as general malaise with widespread musculoskeletal pains) that respond poorly to enzyme replacement treatment. These may indicate fibromyalgia syndrome; if so, other therapeutic options might be more appropriate. AIM: To identify patients with Gaucher's disease for whom fibromyalgia-specific therapy may be therapeutic. DESIGN: Questionnaire-based survey. METHODS: Adult patients (n = 109) with non-neuronopathic Gaucher's disease and adult healthy controls (n = 108) completed health-related questionnaires including the Fibromyalgia Impact Questionnaire, and underwent testing with a dolorimeter to ascertain sensitivity at 22 tender points. RESULTS: Six patients, but no controls, met the criteria for fibromyalgia. Patients with fibromyalgia had a significantly greater incidence of co-morbidities (p = 0.014) relative to other patients with Gaucher's disease; four suffered from bone involvement and were receiving enzyme therapy, but two were untreated. DISCUSSION: The presence of fibromyalgia-specific trigger points may result from multiple aetiologies, or may be an independently-sorting predisposition. Our findings cannot distinguish between these possibilities, but if fibromyalgia were the cause, enzyme replacement therapy would be expensive and inappropriate.

Stability of aneuploid clones during oral squamous cell carcinoma metastasis.

BACKGROUND: The development of aneuploid clones contributes to the expression of metastatic growth properties in head and neck squamous cell carcinomas. Controversy persists as to whether aneuploid clones acquire an autonomous metastatic potential or instead activate diploid tumor cells to disseminate. PATIENTS AND METHODS: DNA flow cytometry was performed on 73 primary oral squamous cell carcinomas and their synchronous lymph node metastases as well as on 20 other patients who experienced delayed manifestation of occult lymph node involvement. RESULTS: Diploidy for both the primary and metastatic tumor was recognized in 6.5% of patients; 5.4% showed a shift from diploidy to aneuploidy while 3.2% had aneuploid tumors that associated with diploid metastases. Aneuploid clones in corresponding lesions were identified in 84.9% of cases. Despite the wide variation of individual DNA contents, 86.1% of the latter group expressed aneuploid clones with identical DNA indices in both the primary and metastatic tumors. The stability of initially established aneuploid clones was monitored even after 58 months of occult metastasis growth. CONCLUSION: Lymph node metastases preferentially originate from pre-existing aneuploid tumor clones.

Gray ramus communicans nerve block: novel treatment approach for painful osteoporotic vertebral compression fracture.

BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common complication of osteoporosis in the aging population. Refractory chronic pain may develop, and few effective treatment options exist. METHODS: We retrospectively analyzed 52 cases in which gray ramus communicans nerve block was used for painful OVCF after failure of conservative analgesic therapy. All were office-based, fluoroscopically guided procedures; a combination of 2% lidocaine and 2% sterile triamcinolone diacetate (Aristocort) was injected on the gray ramus tract of the somatic nerve root corresponding with radiographically documented OVCF. Patient-reported and physician-reported pain scores, analgesic medication use, and overall patient satisfaction were measured. The average follow-up period was 9 months. RESULTS: A 1-point improvement in pain scores was reported by 92% of patients and 88% of physicians; a 4-point improvement was reported by 63% and 58%, respectively. No patients reported increased pain scores; physicians reported increases in two cases. Decreased analgesic requirement was documented in 42%. Patient satisfaction was "high" in 50% and "medium" in 25%. No procedural complications occurred. CONCLUSION: Prompt and sustained improvements in all parameters, especially pain scores, support widespread clinical application of this safe effective and cost-effective therapy.

Multiparameter flow cytometry for simultaneous assessment of p53 protein expression and cellular DNA content in oral squamous cell carcinomas: evidence for the development of aneuploid clones from p53-deficient diploid progenitor cells.

Diploid tumour cells regularly continue to progress after the development of aneuploid cell populations in head and neck squamous cell carcinomas. The coexistence of aneuploid clones with their diploid progenitor cells provides a unique opportunity to study the order of appearance of p53 mutation and aneuploidy in the same tumour. Multiparameter flow cytometry was therefore applied to 22 oral squamous cell carcinomas to simultaneously assess cellular DNA content and p53 protein expression on a single-cell basis. Concurrent measurements of cytokeratin expression served to identify tumour cells of epithelial origin. One of 5 diploid and 2 of 17 aneuploid carcinomas were p53-negative. For 15 p53-positive aneuploid tumours, overexpression of p53 protein was identified for the aneuploid clones as well as for coexisting diploid tumour cell populations in 14 cases. On the understanding that coexisting diploid and aneuploid tumour cell populations have a common clonal origin, these results provide evidence that aneuploid tumour clones typically develop from p53-deficient diploid progenitor cells. Loss of wild-type p53 function may therefore contribute to the development of aneuploidy in head and neck cancer.

High-resolution DNA flow cytometry in oral verrucous carcinoma.

The classification of verrucous carcinoma as an entity unto itself or as a variant of well differentiated squamous cell carcinoma is controversial. To contribute new insights into the biological behavior of this rare tumor, we applied DNA flow cytometry to three node-negative verrucous carcinomas of the oral cavity. All tumors expressed a single aneuploid cell population. One of the patients experienced three courses with local recurrence. All secondary tumors retained the initially established aneuploid clone. The development of aneuploidy is thus a cytogenetic event common to both verrucous and squamous carcinoma of the oral cavity.

Prognostic value of graph theory-based tissue architecture analysis in carcinomas of the tongue.

Several studies on oral squamous cell carcinomas (OSCC) suggest that the clinical value of traditional histologic grading is limited both by poor reproducibility and by low prognostic impact. However, the prognostic potential of a strictly quantitative and highly reproducible assessment of the tissue architecture in OSCC has not been evaluated. Using image analysis, in 193 cases of T1-2 (Stage I-II) OSCC we retrospectively investigated the prognostic impact of two graph theory-derived structural features: the average Delaunay Edge Length (DEL_av) and the average homogeneity of the Ulam Tree (ELH_av). Both structural features were derived from subgraphs of the Voronoi Diagram. The geometric centers of the cell nuclei were computed, generating a two-dimensional swarm of point-like seeds from which graphs could be constructed. The impact on survival of the computed values of ELH_av and DEL_av was estimated by the method of Kaplan and Meier, with relapse-free survival and overall survival as end-points. The prognostic values of DEL_av and ELH_av as computed for the invasive front, the superficial part of the carcinoma, the total carcinoma, and the normal-appearing oral mucosa were compared. For DEL_av, significant prognostic information was found in the invasive front (p < 0.001). No significant prognostic information was found in superficial part of the carcinoma (p = 0.34), in the carcinoma as a whole (p = 0.35), or in the normal-appearing mucosa (p = 0.27). For ELH_av, significant prognostic information was found in the invasive front (p = 0.01) and, surprisingly, in putatively normal mucosa (p = 0.03). No significant prognostic information was found in superficial parts of the carcinoma (p = 0.34) or in the total carcinoma (p = 0.11). In conclusion, strictly quantitative assessment of tissue architecture in the invasive front of OSCC yields highly prognostic information.

Chromosomal composition of aneuploid clones with different DNA contents in head and neck squamous cell carcinomas as determined by combined flow cytometry and fluorescence in situ hybridization.

Studies with DNA flow cytometry (FCM) have shown that DNA contents of aneuploid tumour clones vary in a wide range. The aim of this study was to analyse whether homologous chromosomal changes exist despite the individual differences that may be of general relevance for the development of gross aneuploidy in squamous cell carcinomas of the head and neck. Fluorescence in situ hybridization (FISH) with 13 centromere-specific DNA probes was applied to 3 diploid and 11 aneuploid tumours with DNA indices ranging between 0.8 and 2.2. Disomic and monosomic cell populations were prevalent findings in DNA-diploid tumours. Polysomies were common in aneuploid tumours. Different degrees of aneusomy for identical chromosomes were recurrent features in aneuploid tumours. FISH signal heterogeneity was identified for all chromosomes. The mean number of aneusomic cell populations identified for DNA-aneuploid tumours ranged between 1.6 for chromosome 17 and 3.1 for chromosome 3. Inconsistencies between FISH and FCM data may indicate that centromere-specific DNA probes identify gains and losses of marker DNA due to complex karyotypic rearrangements rather than absolute changes in chromosome numbers. Overall, there was no evidence of the critical involvement of particular chromosomes in the development of different DNA contents.

Progression of diploid tumor cells in aneuploid head and neck squamous cell carcinomas.

The development of aneuploid clones from diploid progenitor cells is a regular characteristic of head and neck squamous cell carcinoma progression. While the significance of aneuploidy formation for the acquisition of invasive and metastatic behavior is well documented, little is known about the contribution of diploid tumor cells after aneuploid clones have emerged. To distinguish diploid cells of epithelial origin from benign cellular components, we applied multiparameter flow cytometry of DNA content and cytokeratin (CK) expression to 36 primary tumors. Twenty-seven carcinomas accommodated aneuploid cell lines that stained positive for CK. All diploid cell populations obtained from aneuploid carcinomas contained CK-positive subpopulations as did all of nine tumors that consisted exclusively of diploid cells. The proportions of CK-positive diploid cells ranged between 6% and 80%, independent of whether they were achieved from entirely diploid or from aneuploid carcinomas. CK-gated diploid and aneuploid cell populations showed largely identical S-phase fractions. These results emphasize that diploid tumor cells regularly persist after the development of aneuploid clones and significantly contribute to local tumor progression. Despite the presence of diploid epithelial cells in aneuploid primary tumors, exclusively the aneuploid clones of eight corresponding lymph node metastases were CK-positive. This provides further evidence of a largely reduced metastatic potential of diploid tumor cells.

DNA aneuploidy by flow cytometry is an independent prognostic factor in squamous cell carcinoma of the oral cavity.

BACKGROUND: The clinical significance of flow cytometric DNA content in head and neck squamous cell carcinoma is still controversial. PATIENTS AND METHODS: We prospectively investigated the prognostic importance of tumor size (T), lymph node involvement at presentation (N), degree of histologic differentiation (G) and DNA ploidy (DNA) in 429 surgically treated patients with primary oral squamous cell carcinoma using multivariate statistics. RESULTS: T, G and DNA were independent predictors of metastasis to the neck. N and DNA were independent prognostic factors of loco-regional recurrence development. N and T were prognostic of overall survival. N and DNA were predictive of recurrence-free survival. For the neck negative group, DNA remained as the only predictor of overall and relapse-free survival. CONCLUSION: DNA flow cytometry adds significant prognostic information beyond that provided by established prognostic factors.

Warthin's tumour is not an Epstein-Barr virus related disease.

BACKGROUND: The histogenesis of Warthin's tumour (WT) is controversial. A possible role for Epstein-Barr virus (EBV) has been suggested. MATERIALS AND METHODS: Twenty formaldehyde-fixed, paraffin-embedded blocks of WT from the parotid gland were examined for the presence of EBV. In situ hybridisation was performed using EBV encoded small nuclear RNAs (EBER1/2) probes labelled with fluorescein isothiocyanate. An EBV-positive P3HR-1 cell line processed to paraffin wax was used as a positive control and a brain section as negative control. RESULTS: EBER1/2 could not be found in the neoplastic epithelial cells in any of the tumours nor in the adjacent normal parotid tissues. Individual positive lymphocytes were present in 7 tumours. CONCLUSIONS: These results indicated that EBV is not involved in the pathogenesis of WT.

High-resolution DNA flow cytometry in papillary cystadenoma lymphomatosum (Warthin's tumour).

Twenty-eight examples of papillary cystadenoma lymphomatosum (Warthin's tumour) of the parotid gland were analysed by high-resolution DNA flow cytometry. The mean coefficient of variation was found to be 1.19% (SD: 0.41). All tumours were DNA diploid. These results did not correspond with expected deviations based on published chromosomal studies. Also, the homogeneously low S-phase fractions (mean: 4.8%; SD: 2.7) found did not support the hypothesis of etiologically distinctive subgroups in these tumours.

Representativity of incisional biopsies for the assessment of flow cytometric DNA content in head and neck squamous cell carcinoma.

DNA flow cytometry studies of squamous cell carcinoma of the head and neck have shown that patients with diploid tumours have favourable prognoses, whereas the outcomes of those with DNA aneuploid tumours are poor. DNA flow cytometry is therefore increasingly used as an integral part of diagnostic procedures. To evaluate how representative biopsies predict the DNA ploidy of oral carcinomas, incisional biopsies taken pretherapeutically from 256 tumours were compared with the corresponding surgical resection specimens. Sixty-six tumours exclusively displayed cells with flow cytometrically diploid DNA content in both the biopsy and the subsequent resection specimen, while 182 carcinomas expressed DNA aneuploid tumour cell lines in matched samples. There were only 8 tumours (3.1%) with heterogeneity in the DNA ploidy status between the biopsy and the resection specimen. These results emphasise the usefulness of incisional biopsies to reliably prognosticate the DNA ploidy status of oral carcinomas.

Correlation between p53 gene mutation, p53 protein labeling and PCNA expression in oral squamous cell carcinomas.

BACKGROUND: The prevalence of oral squamous cell carcinoma (OSCC) among the Black community in South Africa is unacceptably high. The association between p53 protein, and PCNA overexpression and the presence of p53 gene mutations was evaluated. MATERIALS AND METHODS: One hundred and ten formalin-fixed, paraffin-embedded blocks of OSCC were selected for immunohistochemical studies for p53 protein and PCNA expression using the DO-7 and PC10 monoclonal antibodies, respectively. DNA was extracted from fifty-five blocks and exons 5 to 9 of the p53 gene were amplified with nested primers, thereafter sequencing was performed to confirm the presence of mutations detected by single stranded conformational polymorphism. RESULTS: Fifty-six cases (51%) showed p53 expression, while fourteen mutations (25%) were detected. A significant difference was found between the PCNA index in p53 positive and p53 negative tumors while the mean PCNA index for the tumors with p53 mutations was not significantly different from the tumors without mutations. CONCLUSIONS: No association between p53 protein overexpression and p53 gene mutations could be demonstrated.

The significance of DNA flow cytometry in predicting survival and delayed clinical manifestation of occult lymph node metastasis to the untreated neck in patients with oral squamous cell carcinoma.

A total number of 116 clinically neck-negative patients with squamous cell carcinoma of the oral cavity who underwent radical primary tumour surgery without simultaneous neck treatment were entered into this prospective study. The 5 year overall survival rate was 87% for patients with flow cytometrically diploid tumours and 58% for the aneuploid group (P < 0.05). By multivariate survival analysis, tumour stage (P < 0.05) and DNA ploidy (P < 0.05) were significantly associated with the outcome. The cumulative 3 year rate of delayed clinical manifestation of lymph node metastasis to the previously untreated neck was 12.6% for patients with flow cytometrically diploid tumours and 41.3% for the aneuploid group (P < 0.01). By multivariate analysis, the DNA ploidy status of the primary tumour was the only factor among tumour stage, localization and degree of histological differentiation predictive of occult metastasis development (P < 0.05). Also, patients with T1 tumours who frequently are not considered to benefit from elective neck dissection were at high risk of subclinical lymph node involvement if the primary tumours were aneuploid (47%), whereas only 10% of the diploid T1 sample showed occult neck disease. Particularly in patients with less extensive oral carcinomas, DNA aneuploidy is therefore an important decisive factor in elective neck dissection.