Metastasis in pleural mesothelioma. Immunohistochemical markers for disseminated disease.

AIMS: To examine 13 cases of mesothelioma with metastases and compare these with 29 biopsy samples of patients without metastases. Metastatic disease was defined as tumour in which tumour appeared in a different cavity/tissue of the body and which showed no direct spread. Consequently, mediastinal nodal and parenchymal lung spread was excluded. METHODS AND RESULTS: Standard sections were prepared and stained according to the manufacturers' protocols. The antibodies used were MIB-1, nm23, Bcl-2, MMP-9, EMMPRIN (CD147) and alpha-catenin. Scoring employed a grading system (0/1/2/3), and was performed by two pathologists independently. The tissues revealed no significant staining differences for MIB-1, Bcl-2, MMP-9 or EMMPRIN, and therefore no linkage to metastatic potential was determined. Alpha-Catenin showed a diminished level of expression in cases of metastatic mesothelioma (P = 0.024), possibly reflecting dimished catenin-cadherin binding and paralleling data from other tumours. nm23 showed greater staining in metastatic tumours when compared with the controls (P = 0.001). Intriguingly, the nm23 staining pattern was the reverse of that expected. This reversed pattern has been noted before in other tumours and therefore a biological prognostic event may exist for this antibody test and mesothelioma metastasis. CONCLUSION: There may be a place for nm23 and possibly alpha-catenin in immunohistochemical assessment of mesothelioma metastatic potential. However, MIB-1, Bcl-2, MMP-9 and EMMPRIN (CD147) do not show significant staining results.

Offline telepathology diagnosis of colorectal polyps: a study of interobserver agreement and comparison with glass slide diagnoses.

BACKGROUND/AIMS: Technological advances have produced telepathology systems with high quality colour images and reasonable transmission times. Most applications of telepathology have centred on the remote diagnosis of frozen sections or remote real time expert opinions. This study investigates the reproducibility and accuracy of offline telepathology as a primary diagnostic medium for routine histopathology specimens. METHODS: One hundred colorectal polyps (50 hyperplastic, 50 adenomatous) were presented in a randomised order to five histopathologists as offline images on a telepathology workstation. Six images of each case were used: the slide label, a low power scan of all material on the slide, and four higher magnification views. The times taken to prepare the images, and to make the diagnoses, were recorded. Interobserver agreement was measured with kappa statistics and compared with the glass slide diagnoses. RESULTS: The kappa statistics for the interobserver agreement on the telepathology images lay in the range of 0.90-1.00, which is interpreted as excellent agreement, and were significantly higher than those for the glass slide diagnoses (range, 0.84-0.98; p = 0.001). The median time taken to capture the images for a case was 210 seconds. The median time taken to make a diagnosis from the telepathology images was five seconds, which was significantly shorter than for the glass slide diagnoses (median, 13 seconds; p < 0.0005). CONCLUSIONS: Offline telepathology has the potential to be a primary diagnostic medium for routine histopathology with a high degree of reproducibility and short diagnosis times. Further studies are required to validate offline telepathology for different types of specimens and different operators of the image capture system.

Forensic web watch.

The chosen subject for this month's review is toxicology and covers sites touching upon prescription and illicit drugs, analytical techniques and poisonous plants. It highlights a common problem to the user of the Internet. As more and more people log on and put their web site on for public access, searching for a single, comprehensive, all-encompassing single site becomes almost impossible. Many sites are repetitive or purely personal adverts. Unless you are recommended a site or you are prepared to wade your way through all the junk, one will never find the 'El Dorado' you are seeking.

Forensic web watch.

The chosen subject for this month's review is toxicology and covers sites touching upon prescription and illicit drugs, analytical techniques and poisonous plants. It highlights a common problem to the user of the Internet. As more and more people log on and put their web site on for public access, searching for a single, comprehensive, all-encompassing single site becomes almost impossible. Many sites are repetitive or purely personal adverts. Unless you are recommended a site or you are prepared to wade your way through all the junk, one will never find the 'El Dorado' you are seeking.

Low-dose heparin appears safe and can eliminate protamine use for carotid endarterectomy.

OBJECTIVE: To determine the morbidity associated with carotid endarterectomy (CEA) when low doses of heparin (30 U/kg) are used for anticoagulation. This technique eliminates the need for protamine and its potentially deleterious effects on some patients. DESIGN: A retrospective chart review. SETTING: A large academic medical center. PARTICIPANTS: The records of 420 consecutive CEAs in 337 patients (83 bilateral procedures). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The amount of heparin used was less than that used in most reported studies. Eighty-two percent of patients received only 2,000 U of heparin for their entire operation (range, 500 to 3,000 U). Complication rates were low. Neurologic complications included a 0.95% incidence of nonfatal stroke and a 2.1% incidence of transient neurologic deficits that resolved in the first day. There was no mortality. The wounds were described in the postoperative period as dry (96%), swollen (3%), or bloody (1%). No patients received protamine. CONCLUSION: The use of 5 to 10,000 U of heparin will provide anticoagulation for more than an hour. In CEA surgery, anticoagulation for this duration is often unnecessary. A smaller dose of heparin (30 U/kg) can provide adequate anticoagulation for this procedure while eliminating the potentially deleterious effects of protamine use. No additional morbidity was attributed to this technique.

Are giant ganglia a reliable marker of intestinal neuronal dysplasia type B (IND B)?

It has been suggested that giant ganglia are a marker for a developmental bowel disorder, intestinal neuronal dysplasia of the submucosal plexus (IND B), diagnosed in a proportion of patients with severe intractable constipation. Diagnosis of this condition, however, remains controversial with a wide variation in the frequency of diagnosis in different centres. Our aim was to assess the frequency with which giant ganglia could be found in the bowel of individuals who did not give a history of life-long constipation. We also aimed to assess the reproducibility of giant ganglia counts. For this two pathologists independently assessed pieces of normal bowel taken away from the site of the lesion in patients who had undergone surgery for colorectal carcinoma. Giant ganglia containing seven or more ganglion cells were found in 76 and 78% of subjects by each of the two pathologists. There was 1 giant ganglion per 10 ganglia counted in those patients in whom they were identified and 1 giant ganglion per 10.9 ganglia overall. Sections from eight patients in whom there was a history of constipation and/or melanosis coli did not show a greater number of giant ganglia. We conclude therefore that so-called "giant ganglia" are a common feature in the submucosa of normal bowel and that the presence of occasional giant ganglia cannot be considered diagnostic of IND B.

Intravenous lidocaine speeds the return of bowel function, decreases postoperative pain, and shortens hospital stay in patients undergoing radical retropubic prostatectomy.

UNLABELLED: Postoperative ileus is a concern among surgical patients. Epidural anesthesia and analgesia with local anesthetics can decrease the duration of ileus. Significant systemic absorption of local anesthesia occurs during epidural use. In this study, we examined whether many of the beneficial effects on bowel function seen with epidural lidocaine are also present when the drug is given parenterally. Forty patients undergoing radical retropubic prostatectomy were studied with one half of the patients receiving a lidocaine bolus (1.5 mg/kg) and infusion (3 mg/min, unless weight <70 kg, then 2 mg/min); the other half received a saline infusion. A blind observer recorded the patient's daily pain score, the time the patient first experienced flatulence and had the first bowel movement, and the total use of analgesics. Lidocaine-treated patients first experienced flatulence in a significantly shorter time (P < 0.01) than control patients. Lidocaine patients' hospital stay was also significantly shorter (P < 0.05); on average, they spent 1.1 fewer days in the hospital. I.V. lidocaine initiated before anesthesia and continued 1 h postoperatively significantly sped up the return of bowel function. Lidocaine patients were also more comfortable postoperatively. Many of the bowel function benefits attributed to epidural lidocaine are also present when the drug is administered parenterally. Additionally, the length of hospital stay was reduced in lidocaine-treated patients. IMPLICATIONS: This study prospectively examined whether I.V. lidocaine could affect the return of bowel function after radical prostate surgery. Lidocaine-treated patients had shorter hospital stays, less pain, and faster return of bowel function. In this population, lidocaine infusion can be a useful adjunct in anesthetic management.

A future role for the pulmonary artery catheter?

Either a moratorium prohibiting, or a prospective, randomized clinical trial on pulmonary artery catheter use has been proposed. Expert opinion regarding both this suggestion and on the therapeutic efficacy of interventions guided by pulmonary artery catheters in a variety of clinical settings has included (in my view incorrectly) physician prerogative and perceived threats to therapeutic freedom. The legitimate concerns of worsened patient outcome secondary to pulmonary artery catheter use and demonstrably inadequate intellectual preparation of practitioners and allied healthcare professionals, which may exacerbate these deficiencies, have also been discussed. The future of the pulmonary artery catheter is questioned; physicians must evaluate the available information and, more importantly, critique their current practice, before employing this technology.

At the coalface--medical ethics in practice. First, do no harm.

When a physician acts as both doctor and researcher conflicts can develop. When a doctor does not know whether a patient is taking active drug or placebo, any new medical problems can result in a dilemma. Is the patient's suffering a side effect of the medication or is this a new medical problem? Mrs W's case demonstrates the problem that can occur when the physician is blinded in the name of research.

Pressure support ventilation with the laryngeal mask airway: a method to manage severe reactive airway disease postoperatively.

The use of a laryngeal mask airway (LMA) and a bi-level positive airway pressure (BiPAP) machine is described in a post-operative thoracotomy patient with reactive airway disease. The LMA was placed to avoid reintubation of the trachea after a double lumen tube was no longer necessary. Placement in an awakening patient and positive-pressure ventilatory support were well tolerated and did not trigger a bronchospastic response. The patient was able to cough and breathe deeply with the LMA while receiving ventilatory assistance in the post-anaesthesia care unit (PACU). The LMA is a therapeutic option to tracheal reintubation in patients who need postoperative ventilatory support after one-lung anaesthesia.

Role of endogenous cytokines in endotoxin- and interleukin-1-induced pulmonary inflammatory response and oxygen tolerance.

Endotoxin lipopolysaccharide and the cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), are known to protect adult rats against O2 toxicity. However, whether the effect of endotoxin is mediated by these cytokines is not clear. We have previously demonstrated that depletion of 84% rat alveolar macrophages (AM), which reduced lipopolysaccharide (LPS)-induced release of TNF by 86%, had no effect on LPS-induced O2 tolerance. In this study, we demonstrated that coinsufflation of LPS with anti-TNF antibody and IL-1 receptor antagonist (IL-1ra), which completely inhibited LPS-induced TNF and IL-1 activities, had no effect on LPS-induced alveolar inflammatory response and O2 tolerance. Likewise, coinsufflation of IL-1 and anti-TNF antibody, which completely neutralized IL-1-induced TNF activity, had no effect on IL-1-induced alveolar inflammatory response and O2 tolerance. In contrast, IL-1ra completely abolished IL-1-induced inflammatory response and markedly inhibited IL-1-induced O2 tolerance. These results suggest that LPS-induced alveolar inflammatory response and O2 tolerance are not mediated by endogenous TNF and IL-1. Similarly, endogenous TNF does not mediate IL-1-induced alveolar inflammatory response and O2 tolerance.

Cardiopulmonary bypass: risk management concerns for the anesthesiologist.

Perfusionists have a critically important role in cardiac surgery. Their responsibilities include providing cardiovascular support, maintaining adequate blood flow and blood pressure, maintaining adequate oxygenation, operating suction pumps and other devices, regulating blood temperature, and keeping records. The relationship between perfusionist and anesthesiologist as members of the cardiac surgical team should be one of mutual support. Although many anesthesiologists do not control the pharmacology of perfusion, it is their responsibility to ensure that the perfusionist understands the pharmacopeia being used and to know what the perfusionist is administering. In-depth knowledge of the techniques and practices of cardiopulmonary perfusion is a prerequisite for cardiac anesthesiologists. The future is likely to see an increasingly supportive relationship between anesthesiologists and perfusionists.

Protection against oxygen toxicity by tracheal insufflation of endotoxin: role of Mn SOD and alveolar macrophages.

Endotoxin and the cytokines, tumor necrosis factor and interleukin-1, are known to protect adult rats against O2 toxicity. However, whether the effect of endotoxin is mediated through its direct effect on lung cells or through cytokines is not clear. In this study, we demonstrated that endotoxin at a dosage of 5 micrograms/rat (14-20 micrograms/kg) attenuated O2-induced pulmonary injury and markedly prolonged the survival of rats exposed to 100% O2. Endotoxin was more protective when given by intratracheal insufflation or intravenous injection than by intraperitoneal injection. The endotoxin-induced O2 tolerance was associated with a selective enhancement of pulmonary manganese superoxide dismutase, but not Cu,Zn SOD, mRNA. In addition, depletion of 84% rat alveolar macrophages by liposome-encapsulated dichloromethylene diphosphonate, resulted in a marked reduction (86%) of endotoxin-induced release of tumor necrosis factor into the alveolar space. However, endotoxin was still protective in these alveolar macrophage-depleted animals.