Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.

CHK1 inhibition in soft-tissue sarcomas: biological and clinical implications.

Background: Inhibition of ChK1 appears as a promising strategy for selectively potentiate the efficacy of chemotherapeutic agents in G1 checkpoint-defective tumor cells such as those that lack functional p53 protein. The p53 pathway is commonly dysregulated in soft-tissue sarcomas (STS) through mutations affecting TP53 or MDM2 amplification. GDC-0575 is a selective ATP-competitive inhibitor of CHK1. Methods: We have performed a systematic screening of a panel of 10 STS cell lines by combining the treatment of GDC-0575 with chemotherapy. Cell proliferation, cell death and cell cycle analysis were evaluated with high throughput assay. In vivo experiments were carried out by using TP53-mutated and TP53 wild-type patient-derived xenograft models of STS. Clinical activity of GDC-0575 combined with chemotherapy in patients with TP53-mutated and TP53 wild-type STS was also assessed. Results: We found that GDC-0575 abrogated DNA damage-induced S and G2-M checkpoints, exacerbated DNA double-strand breaks and induced apoptosis in STS cells. Moreover, we observed a synergistic or additive effect of GDC-0575 together with gemcitabine in vitro and in vivo in TP53-proficient but not TP53-deficient sarcoma models. In a phase I study of GDC-0575 in combination with gemcitabine, two patients with metastatic TP53-mutated STS had an exceptional, long-lasting response despite administration of a very low dose of gemcitabine whereas one patient with wild-type TP53 STS had no clinical benefit. Genetic profiling of samples from a patient displaying secondary resistance after 1 year showed loss of one preexisting loss-of-function mutation in the helical domain of DNA2. Conclusion: We provide the first preclinical and clinical evidence that potentiation of chemotherapy activity with a CHK1 inhibitor is a promising strategy in TP53-deficient STS and deserves further investigation in the phase II setting.

Routine histopathological examination after female-to-male gender-confirming mastectomy.

BACKGROUND: The number of transmen seeking gender-confirming surgery has risen steadily throughout the last decade. Pathologists are increasingly confronted with transmale mastectomy specimens. It is not clear whether routine histopathological examination is useful. This study explored the possible benefit of routine investigation through detailed description of lesions encountered in mastectomy specimens after female-to-male gender-confirming surgery. METHODS: Breast tissue from a cohort of transmen was reviewed. The presence of benign and malignant breast lesions was recorded. The number of terminal duct-lobule units (TDLUs) per ten low-power fields (LPFs) was quantified. Information on hormone therapy and morphometry was retrieved for selected patients. RESULTS: The cohort included 344 subjects with a mean age of 25·8 (range 16-61) years at the time of surgery; the age at surgery decreased significantly over time. Older individuals presented with a significantly higher number of breast lesions. The number of TDLUs per LPF was lower in heavier breasts, but did not correlate with age. Breast lesions, either benign or malignant, were present in 166 individuals (48·3 per cent). Invasive breast cancer was found in two (0·6 per cent); one tumour was an unexpected finding. The number of breast lesions encountered on histopathological examination increased significantly when more tissue blocks were taken. CONCLUSION: The discovery of an unexpected breast cancer in a 31-year-old transman emphasizes the importance of thorough routine histopathological examination of mastectomy specimens. The number of tissue blocks taken should be based on age and breast weight.

Moderate hypofractionated radiotherapy for prostate cancer: 3-year toxicity results of a multicentre randomized phase 3, non-inferiority trial.

BACKGROUND AND PURPOSE: Moderate hypofractionated radiotherapy (HFRT) is a standard treatment for prostate cancer patients. We compared 2 moderate HFRT regimens, with a biologically equivalent dose of 80 Gy in 2 Gy fractions, with a modest simultaneous integrated boost to the dominant intraprostatic lesion. MATERIAL AND METHODS: This is a multicenter, non-inferiority, randomized phase 3 trial with acute toxicity as the primary endpoint, comparing: 56 Gy in 4 weeks (16x3.5 Gy, 4 days/week, Arm A) with 67 Gy in 5 weeks (25x2.68 Gy, 5 days/week, Arm B). The H0 hypothesis is that both regimens are equivalent in terms of acute grade ≥ 2 gastro-intestinal toxicity, defined as a difference in acute grade ≥ 2 gastro-intestinal toxicity of ≤ 10 %. Here we report on acute and late toxicity. RESULTS: We included 170 patients in Arm A and 172 patients in Arm B. The median follow-up time for all patients was 42 months. Acute grade ≥ 2 gastrointestinal toxicity was reported by 24 % of patients in both groups. Acute grade 2 and 3 urinary toxicity was observed in 52 % and 9 % of patients in Arm A and 53 % and 7 % in Arm B. Late grade 2 and grade ≥ 3 gastrointestinal toxicity occurred in 19 % and 4 % of patients in Arm A compared with 15 % and 4 % in Arm B. Late grade 2 and grade ≥ 3 urinary toxicity was observed in 37 % and 10 % of patients in Arm A and 36 % and 6 % in Arm B. CONCLUSION: This analysis confirms that both HFRT regimens are safe and equivalent in terms of acute grade ≥ 2 gastrointestinal toxicity.

An unusual tumour causing neonatal respiratory distress.

PROBLEM: We present the case of a term neonate referred shortly after birth because of breathing and feeding difficulties. METHODOLOGY: Fiber-endoscopic examination of the nasal cavity showed a pendulating mass in the nasopharynx. RESULTS: A complete surgical resection was performed and the baby recovered completely. Microscopic examination of the mass showed an overlying non-keratinized squamous cell lining with an atypical cell population in some fragments. Histological features were compatible with a high-grade epithelial tumour like a midline carcinoma, but a final diagnosis of a salivary gland anlage tumour was established. CONCLUSION: Flexible fiber endoscopy is the method of choice for examining the nasal passages and oropharynx in neonates with respiratory distress. Congenital salivary gland anlage tumour is a rare cause of neonatal nasal obstruction; it is benign and complete excision results in a cure. Histologically, it may mimic a malignant tumour owing to the high mitotic index.

Adjuvant Radiotherapy After Radical Cystectomy for Patients with High-risk Muscle-invasive Bladder Cancer: Results of a Multicentric Phase II Trial.

BACKGROUND: High-risk muscle-invasive bladder cancer (MIBC) has a poor prognosis. Old trials showed that external beam radiotherapy (EBRT) after radical cystectomy (RC) decreases the incidence of local recurrences but induces severe toxicity. OBJECTIVE: To evaluate the toxicity and local control rate after adjuvant EBRT after RC delivered with volumetric arc radiotherapy. DESIGN, SETTING, AND PARTICIPANTS: This is a multicentric phase 2 trial. From August 2014 till October 2020, we treated 72 high-risk MIBC patients with adjuvant EBRT after RC. High-risk MIBC is defined as ≥pT3-MIBC ± lymphovascular invasion, fewer than ten lymph nodes removed, pathological positive lymph nodes, or positive surgical margins. INTERVENTION: Patients received 50 Gy in 25 fractions with intensity-modulated radiotherapy to the pelvic lymph nodes ± cystectomy bed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome is acute toxicity. We report on local relapse-free rate (LRFR), clinical relapse-free survival (CRFS), overall survival (OS), and bladder cancer-specific survival (BCSS). RESULTS AND LIMITATIONS: The median follow-up is 18 mo. Forty-two patients (61%) developed acute grade 2 gastrointestinal (GI) toxicity. Four patients (6%) had acute grade 3 GI toxicity. One patient had grade 5 diarrhea and vomiting due to obstruction at 1 mo. Two-year probabilities of developing grade ≥3 and ≥2 GI toxicity were 17% and 76%, respectively. Urinary toxicity, assessed in 17 patients with a neobladder, was acceptable with acute grade 2 and 3 urinary toxicity reported in 53% (N = 9) and 18% (N = 3) of the patients, respectively. The 2-yr LRFR is 83% ± 5% and the 2-yr CRFS rate is 43% with a median CRFS time of 12 mo (95% confidence interval: 3-21 mo). Two-year OS and BCSS are 52% ± 7% and 62% ± 7%, respectively. Shortcomings are the nonrandomized study design and limited follow-up. CONCLUSIONS: Adjuvant EBRT after RC can be administered without excessive severe toxicity. PATIENT SUMMARY: In this report, we looked at the incidence of toxicity and local control after adjuvant external beam radiotherapy (EBRT) following radical cystectomy (RC) in high-risk muscle-invasive bladder cancer patients. We found that adjuvant EBRT was feasible and resulted in good local control. We conclude that these data support further enrollment of patients in ongoing trials to evaluate the place of adjuvant EBRT after RC.

Massive swelling of Surgicel® Fibrillar™ hemostat after spinal surgery. Case report and a review of the literature.

BACKGROUND: Oxidized regenerated cellulose is commonly used in many surgical fields as a hemostatic agent. Complications related to swelling or compression after application of small portions of Surgicel® Fibrillar™ have not yet been described. PATIENTS: We report on a 65-year-old woman who was operated for a high-grade spinal stenosis at the L2-L3 level. Small portions of Surgicel® Fibrillar™ were used to control bleeding from the epidural venous plexus. The immediate postoperative course was uneventful. However, one day after surgery, the patient complained about progressive worsening pain at the operated level. A non-contrast lumbar CT scan showed no evidence of a postoperative hematoma or other complication. MR imaging showed a horseshoe-shaped mass compressing the dural sac at the operated level from posterior and both sides. Because we suspected a postoperative hematoma, the patient was re-operated. No hemorrhage was seen but instead we found large, swollen firm pieces of Surgicel® Fibrillar™ compressing the dural sac. These pieces were removed. RESULT: Postoperatively no neurological deficit or pain was present. Histological examination of the removed mass of Surgicel® Fibrillar™ revealed only the presence of blood, fibrin and an amorphous eosinophilic content. There was no sign of any inflammation. CONCLUSION: On the basis of this experience, we advise caution with the use of hemostatic agents during spinal surgery and - if used - strongly advise the removal of Surgicel® Fibrillar™ after the hemostasis has been achieved to avoid the development of complications due to a mass effect.

GSK3-beta as a candidate therapeutic target in soft tissue sarcomas.

Soft tissue sarcoma (STS) is a predominantly fatal rare malignancy with inadequate treatment options. Glycogen synthase kinase 3ß (GSK-3ß) is an emerging target in human malignancies. Its therapeutic relevance in STS is unknown. We analyzed the prognostic impact of GSK-3ß gene and protein expression in two independent cohorts of patients with STS. We then treated STS cell lines and mice xenografts with a novel GSK-3 inhibitor 9-ING-41 alone or in combination with chemotherapy. We demonstrated that 9-ING-41 treatment induced significant STS cells apoptosis and was synergistic in vivo when combined with chemotherapy. Mechanistically, 9-ING-41 induces significant apoptosis of STS cells via suppression of NF-κB-mediated X-linked inhibitor of apoptosis protein (XIAP) expression. These data support the inclusion of patients with STS in clinical studies of 9-ING-41 alone and in combination with chemotherapy.

Impression cytology of melanocytic conjunctival tumours using the Biopore membrane.

PURPOSE: To compare a new Biopore membrane impression cytology method with the routinely used exfoliative cytology in patients with a melanocytic lesion of the conjunctiva. METHODS: Sixty-eight consecutive patients with a conjunctival melanocytic lesion underwent Biopore membrane impression cytology as well as exfoliative cytology. A histologic sample was also available in 26 cases. All Biopore samples were stained immediately with RAL 555. Both Biopore and exfoliative cytology samples were assessed by two cytopathologists and graded into four different categories of atypia. RESULTS: Twenty-three out of 26 Biopores and 20 out of 24 for the exfoliative smears correlated with the corresponding histologic sample. Biopore cytology resulted in higher numbers of cells with a greater density compared to exfoliative cytology. CONCLUSIONS: Biopore cytology can be used for cytologic sampling of conjunctival melanocytic lesions. Because of the larger amount and higher density of cells obtained with the Biopore membrane, interpretation by a pathologist is easier and faster. Sampling of the fornix, caruncula, and ocular material in children is difficult with the Biopore method, and exfoliative cytology seems to be the favorable test in those situations.

[Pitfalls for renogram interpretation in pediatric urology]. / Biais d'interprétation de la scintigraphie rénale chez l'enfant.

Renograms are currently used for functional assessment by pediatric urologists. The aim of the present work was to focus on the potential pitfalls concerning renography. Potential confounding factors are described in reference to concrete cases. The main types of pitfalls concern venous or urinary catheters and background area definition. Protocols and renogram interpretation are critiqued in a bibliographic review. We propose a technical update and original data on the potential pitfalls in renography interpretation. Multidisciplinary discussion between nuclear medicine, pediatrics and pediatric surgery departments is required before drawing conclusions.

HCV core protein augments cyclosporine immunosuppression.

Hepatitis C viremia occurs universally after liver transplantation. It is speculated that soluble HCV proteins may be immunomodulatory. We measured the effects of HCV core upon human T-cell proliferation, expression of activation markers, and interaction with cyclosporine. Cells were activated with anti-CD3 for 2-6 days. Cultivation with 1, 2, 4, and 8 microg/mL core reduced tritiated thymidine uptake by 7% (P = ns), 63% (P < .001), 69% (P < .001) and 92% (P < .001). Direct cell counting (10(4)) showed proliferative inhibition in treated cultures after 2 days (84%, P < .05), 4 days (93%, P < .05), and 6 days (88%, P < .05). Viability remained greater than 90%. Expression of activation markers was reduced with core treatment. Treatment with 4 microg/mL core for 2, 4, and 6 days reduced CD2+CD25+ by 67% (P < .05), 67% (P < .05), and 51% (P < .05) and CD2+DR+ expression by 54% (P < .05), 46% (P < .05), and 54% (P < .05). Interaction between core and cyclosporine was determined by isobologram analysis which determines whether interactions are synergistic, additive or antagonistic. Combining core with cyclosporine resulted in an additive effect upon proliferative suppression. Linear regression confirmed an additive interaction with an r2 value of 0.98. The data shows that soluble core causes dose dependent suppression of T-cell proliferation and may potentiate suppression by cyclosporine.

Influenza vaccination does not promote cellular or humoral activation among heart transplant recipients.

BACKGROUND: The impact of influenza vaccination on in vitro parameters of cellular and humoral immunity, anti-viral titers, and clinical outcome was evaluated among cardiac transplant recipients. METHODS: Blood was collected from 29 patients before and 3-4 weeks after influenza vaccination and tested for phenotypic changes in lymphoid subpopulations and generation of antibodies against the allograft and vaccine. RESULTS: Vaccination did not change the percentage of lymphoid subpopulations and did not induce generation of anti-HLA alloantibodies. Anti-vaccine response was detected in 12 of 29 patients and did not correlate with rejection history, length of graft survival, or immunosuppressive therapy. Vaccination did not change the frequency of rejection. Flu-like symptoms were reported in one patient but not confirmed microbiologically. CONCLUSION: Despite the small number of patients in the study, influenza vaccination did not induce undesirable side effects, such as graft rejection or allo-sensitization. Generation of a positive anti-vaccine response was lower among the transplant recipients than healthy volunteers (41% vs. 80%). Clinical efficacy of the vaccine among the responders was not evaluated.

Effect of Lactobacillus ingestion on the gastrointestinal mucosal barrier alterations induced by indometacin in humans.

BACKGROUND: Chronic nonsteroidal anti-inflammatory drug (NSAID) ingestion strongly affects the gastrointestinal mucosa as a first stage before ulceration. Some Lactobacillus strains may stabilize the mucosal barrier by increasing mucin expression, reducing bacterial overgrowth, stimulating mucosal immunity and synthetizing antioxidant substances; these events are altered in NSAID-associated gastroenteropathy. AIM: To determine whether ingestion of the probiotic Lactobacillus GG (LGG) protects the gastrointestinal mucosa against indometacin-induced alterations of permeability. SUBJECTS AND METHODS: Four gastrointestinal permeability tests were carried out in random order in 16 healthy volunteers: (i) basal; (ii) after indometacin; (iii) after 5 days of living LGG ingestion before indometacin administration; (iv) after 5 days of heat-killed LGG ingestion before indometacin administration. RESULTS: Indometacin significantly increased basal sucrose urinary excretion (29.6 mg [17.1-42.1] vs. 108.5 mg [68.2-148.7], P=0.0030) (means [95% CI]) and lactulose/mannitol urinary excretion (1.03% [0.73-1. 32] vs. 2.93% [1.96-3.90], P=0.00012). Heat-killed LGG did not modify the indometacin-induced increase of gastrointestinal permeability, while live bacteria significantly reduced the alteration of gastric (47.8 mg [31.1-64.6], P=0.012) but not intestinal permeability induced by NSAID. CONCLUSIONS: Regular ingestion of LGG protects the integrity of the gastric mucosal barrier against indometacin, but has no effect at the intestinal level.

Alpha interferon combined with ribavirin potentiates proliferative suppression but not cytokine production in mitogenically stimulated human lymphocytes.

The improved clinical outcome observed among patients with hepatitis C treated with the combination of alpha interferon (IFN) and ribavirin (RBV) is presumed to result from immunomodulation and viral inhibition. However, the impact of the drug combination upon lymphocyte activity is unknown. The present study evaluated the effects of IFN and RBV, singly and in combination, upon proliferation, cell cycle sensitivity and cytokine elaboration following PHA stimulation of lymphocytes. Two formulations of IFN, interferon-a-2b (IFN-2b) and interferon-a-con-1 (CIFN), were included. Titration of each drug over a wide range of concentrations showed dose dependent proliferative suppression without cytotoxicity. Proliferation was suppressed 57-99% (P<0.001) by IFN-2b (10(5)-10(7) IU/ml), 41-74% (P<0.001) by CIFN (1.5-150 ng/ml), and 10-94% (P<0.001) by RBV (0.5-50 microg/ml). Isobologram analysis showed that the interaction between IFN-2b and RBV on proliferative suppression was additive. In contrast, the interaction between CIFN and RBV was weakly antagonistic. Proliferative suppression by both the IFNs was cell cycle restricted. IFN-2b and CIFN added at the onset of PHA stimulation (G0/G1) versus 24 h later (S phase) inhibited proliferation by 50 versus 5%, respectively (P<0.05). The onset of IFN resistance correlated with a 50% reduction (P<0.05) in IFN receptors on the cell surface. In contrast, RBV caused equivalent proliferative suppression (P=NS) when added at any time during PHA activation. Cytokine secretion after 24 h of PHA stimulation showed that IFN-2b versus CIFN increased the secretion of IL2, TNF and gamma IFN by 4.5-, 4.1- and 8.3-fold (P<0.005) versus 1-, 1.9- and 1.9-fold (P<0.05), respectively, above control levels. Neither IFN affected IL10 secretion. RBV, singly and in combination with IFN, had no impact on cytokine expression (P=NS). This study identifies several potential mechanisms by which the combination of IFN and RBV may exert a more potent effect upon cellular immunity than either agent alone and shows that different formulations of IFN may have non-identical effects upon lymphocyte responses.

Basement membrane and connective tissue proteins in intestinal mucosa of patients with coeliac disease.

AIMS: Gluten ingestion in coeliac disease is associated with alterations of the intestinal mucosa, especially the expansion of the lamina propria. Antiendomysium and antireticulin antibodies may result from interactions between gliadin and extracellular matrix components. By behaving as autoantigens, connective tissue proteins could initiate mucosal damage. This study evaluates changes in the distribution of laminin, type IV collagen, and fibronectin in the mucosa of patients with coeliac disease in an attempt to explain the alterations of mucosal morphology. METHODS: Intestinal biopsies were obtained from patients with coeliac disease on admission and while on a gluten free diet. The distribution of type IV collagen, laminin, fibronectin, and alpha-smooth muscle actin was evaluated by immunofluorescence and by immunogold labelling and electron microscopy. RESULTS: In patients with coeliac disease, the intensity of type IV collagen, laminin, and fibronectin immunofluorescent staining was decreased and less well defined than in controls, with frequent breaches in the basement membrane; fibronectin staining was weak in the distal third of the elongated crypts and absent under the flat surface. The distribution of smooth muscle fibre in the distal lamina propria of flat mucosae was altered. The distribution of these proteins was normal as assessed by immunoelectron microscopy. CONCLUSIONS: The intensity of staining of some components of the basement membrane is decreased in coeliac disease and the distribution of smooth muscle fibres is altered. These changes may result from interactions between gliadin and components of the extracellular matrix and may play a role in the genesis of mucosal lesions and in the damage to the epithelium.

Tailgut cysts: rare retrorectal tumours.

Two patients presented with tailgut cysts. The first patient complained of pain and pressure in the sacrococcygeal region. The second patient had developed a cystic mass superficial to the coccyx. Pelvic CT scans of both patients demonstrated a retrorectal mass. Both tumours were excised through a posterior para-sacrococcygeal approach with resection of the coccyx.

Transmanubrial osteomuscular sparing approach for sulcus superior tumours.

OBJECTIVE: The authors report their initial experience with the transmanubrial osteomuscular sparing approach for resection of sulcus superior tumours. The feasibility of this technique is evaluated. PATIENTS: Between February 2000 and March 2002 three patients with sulcus superior tumours were surgically treated using the transmanubrial osteomuscular sparing approach. The first two patients had a non-small cell carcinoma of the upper lobe. In the third patient a pathological diagnosis of a plasmocytoma of the first rib was made. In two cases the first thoracic root was resected. RESULTS: In two patients a complete R0 resection was achieved. However, an additional posterolateral thoracotomy was necessary in two patients because the costovertebral angle was difficult to address. In one patient final histologic examination found microscopically positive margins. CONCLUSION: We believe that the transmanubrial osteomuscular sparing technique enables us to approach and control the subclavian vessels and brachial plexus in an oncologically responsible way and permits a radical resection of tumours invading the thoracic inlet.

[Chemical pneumonia in children]. / Chemische pneumonie bij kinderen.

Between 1980 and 1989 the Children's Hospital of Antwerp admitted 954 children with signs of intoxication. In 83 cases (9%) these were due to ingestion of hydrocarbons, 17 of these 83 children (21%) had chemical pneumonia. The most frequent chemicals were turpentine, petrol and lamp oil. The main symptoms were vomiting, skin rash, coughing and fever accompanied by an infectious blood count. Roentgen abnormalities in this group were less frequent than reported in the literature. A chest X-ray immediately after admission does not always provide information about pneumonia because abnormalities may already be present, e.g. due to an acute lung condition; nevertheless it is necessary for further study, if any. An X-ray after 24 hours is indispensable to confirm or exclude chemical pneumonia. As regards treatment, only supportive therapy is possible. Pulmonary function studies after a few weeks may be useful. A survey is presented of the epidemiology, clinical findings, diagnostics, pathophysiology, symptomatic therapy, prevention and prognosis.

Treatment of unstable fractures, dislocations and fracture-dislocations of the cervical spine with Senegas plate fixation.

The results of the anterior approach to the cervical spine for the treatment of fractures and dislocations by arthrodesis and Senegas plate fixation are described. Twenty-two patients underwent a one- or two-level arthrodesis of the cervical spine. Their mean age was 42 years. The injuries were subdivided using the radiological classification described by Harris. In the group of patients who presented with a complete neurological deficit below the level of injury, there was only one patient who deteriorated. X ray examination 1 year after surgery showed fusion in 17 patients (100%). In contrast to some recent cadaveric and animal studies in which the anterior approach and fixation were found to be less stable than posterior fusion, our results obtained with this method are excellent, despite the fact that post-operative immobilization was limited. Problems with the anterior approach did not arise in these 22 patients. Alignment was always acceptable and fusion was achieved within one year in all cases.