Impact of EBUS-TBNA on modalities for tissue acquisition in patients with lung cancer.

BACKGROUND: The impact of the introduction of Endobronchial ultrasound with real-time guided transbronchial needle aspiration (EBUS-TBNA) on the use of diagnostic modalities for tissue acquisition in patients with lung cancer is unknown. METHODS: A retrospective review of 328 consecutive patients diagnosed with lung cancer at a university teaching hospital, where they first presented in London in 2007, 2009 and 2011. EBUS was introduced in 2008. RESULTS: In total, 316 patients were included in the analysis. Comparing 2007 with 2011 data, there has been a significant reduction in standard bronchoscopy (P < 0.0001) and mediastinoscopy (P = 0.02). The proportion of cases diagnosed by EBUS-TBNA significantly increased from 0% in 2007 to 26.7% in 2009 and 25.4% in 2011 (P < 0.0001). In the same period there has also been an increased trend in the proportion of patients going directly to surgery without pathological confirmation with a 9.6% increase in diagnoses obtained at thoracotomy (P = 0.0526). CONCLUSION: The use of diagnostic modalities that provide information on diagnosis and staging in a single intervention are increasing. At our hospital, the use of EBUS-TBNA for providing a lung cancer diagnosis is increasing and this has led to a significant reduction in standard bronchoscopies and mediastinoscopies. These changes in practice may have implications for future service provision, training and commissioning.

Microdissection molecular copy-number counting (microMCC)--unlocking cancer archives with digital PCR.

Most cancer genomes are characterized by the gain or loss of copies of some sequences through deletion, amplification or unbalanced translocations. Delineating and quantifying these changes is important in understanding the initiation and progression of cancer, in identifying novel therapeutic targets, and in the diagnosis and prognosis of individual patients. Conventional methods for measuring copy-number are limited in their ability to analyse large numbers of loci, in their dynamic range and accuracy, or in their ability to analyse small or degraded samples. This latter limitation makes it difficult to access the wealth of fixed, archived material present in clinical collections, and also impairs our ability to analyse small numbers of selected cells from biopsies. Molecular copy-number counting (MCC), a digital PCR technique, has been used to delineate a non-reciprocal translocation using good quality DNA from a renal carcinoma cell line. We now demonstrate microMCC, an adaptation of MCC which allows the precise assessment of copy number variation over a significant dynamic range, in template DNA extracted from formalin-fixed paraffin-embedded clinical biopsies. Further, microMCC can accurately measure copy number variation at multiple loci, even when applied to picogram quantities of grossly degraded DNA extracted after laser capture microdissection of fixed specimens. Finally, we demonstrate the power of microMCC to precisely interrogate cancer genomes, in a way not currently feasible with other methodologies, by defining the position of a junction between an amplified and non-amplified genomic segment in a bronchial carcinoma. This has tremendous potential for the exploitation of archived resources for high-resolution targeted cancer genomics and in the future for interrogating multiple loci in cancer diagnostics or prognostics.

Clonal divergence in lung cancer development is associated with allelic loss on chromosome 4.

Patients who receive curative treatment for lung cancer can develop additional lung tumors that may or may not be related to the original tumor and thus require different clinical management. If a subsequent tumor has a pattern of allele loss, revealed by allelotype analysis, overlapping that of the first tumor, it is believed to be a local recurrence or metastasis. In this case history, we present loss of heterozygosity analyses of the original primary tumor, and two second primary tumors occurring in the ipsilateral and the contra-lateral lungs. The allelotyping suggests that these tumors are all clonally related but concordance is not complete. Our interpretation is that the original primary tumor and the two new primary tumors have developed to full malignancy independently, but are clonally related, possibly via a clone of motile progenitor cells. Deletion mapping of DNA from biopsies of this patient delineated a region in 4p16 that we had previously shown to be lost in the transition from carcinoma in situ to invasive tumor. We identified a minimally deleted region encompassing six genes including two candidate tumor suppressor genes, CRMP1 a lung cancer metastasis-suppressing gene and PPP2R2C a gene for a regulatory subunit of the PP2 complex known to suppress tumorigenesis, particularly viral induced transformation.

Upper airways sarcoidosis presenting as obstructive sleep apnoea.

Sarcoidosis may present in a number of different ways, affecting many organ systems. The case history is presented of a 32 year old woman who presented with symptoms of severe obstructive sleep apnoea (OSA) due to infiltration of the upper airway by sarcoidosis. To our knowledge this presentation of sarcoidosis has not previously been described.

Clinical spectrum and mortality of extradural haematoma in rural versus urban India.

This study comprised of 340 cases of extradural haematomas (EDHs) treated during a period of 10 years (1984-1994) in the division of Neurosurgery, Institute of Medical Sciences, Varanasi. Majority of them were rural patients (55.9 percent). The commonest mode of injury was blunt impact to the head mainly by lathi in rural India (48.4 percent), and road traffic accidents in urban population (60 percent). Only 12 percent of patients reached hospital within 6 hours of injury. Outcome is better in rural cases (11.5 percent) inspite of late reporting to the hospital. Such cases are not usually associated with other injuries as impact is focal. Clot with less than 50 ml, 50-100 ml and more than 100 ml had mortality rate 0 percent, 12.5 percent and 18.7 percent respectively; similarly outcome became poorer with increasing midline shift in computed tomography scan (1-4 mm: 0 percent, 5-9 mm: 9.2 percent and 10 mm or more: 29.8 percent). The common site of EDH is temporal (42.2 percent) in urban and parietal (51.6 percent) in rural patients.

Preoperative laser therapy in a patient with resectable bronchogenic carcinoma and severe coronary artery disease.

A 67 year old man with severe coronary artery disease was found to have a resectable bronchogenic carcinoma. Myocardial revascularisation and lung resection were considered to be unduly hazardous as either separate or combined operations. Preoperative laser therapy, however, enabled the two procedures to be performed in greater safety in the most appropriate sequence.

Role of the Gianturco expandable metal stent in the management of tracheobronchial obstruction.

This paper reports our experience in treating localized airway obstruction with expandable metal stents. Nine patients were treated for malignant obstruction and 6 for benign obstruction. The main indications for treatment were imminent asphyxia, breathlessness and/or repeated chest infections. All but 2 patients had received other treatments before referral. Seven patients with malignant obstruction had extrinsically compressed airways and all derived a sustained symptomatic improvement. Two patients with recurrent tracheal obstruction caused by intraluminal tumor gained lasting relief with the use of a covered expandable metal stent. All 6 patients with benign strictures were improved, although 2 developed recurrent obstruction caused by granulation tissue growing within and beyond the stent. It is concluded that the expandable metal stent provides an effective and noninvasive method of relieving large airway obstruction. As the long-term tissue tolerance to this type of stent is not known, caution is advised in the management of benign strictures. In patients with malignant obstruction, however, the expandable metal stent would appear to have considerable potential as a palliative treatment.

Susceptibility status of five species of Japanese encephalitis vectors to insecticides from Kolar district, Karnataka.

Susceptibility tests were conducted on the adults of five species of mosquito vectors of Japanese encephalitis (JE) viz., Culex tritaeniorhynchus, C. vishnui, C. pseudovishnui, C. gelidus and C. fuscocephala from Kolar district, Karnataka during 1990-91 against organo chloride compounds (DDT 4%, dieldrin 4%), organo phosphate compounds (malathion 5%, fenitrothion 1.0%), carbamate (propoxur 0.1%) and pyrethroid (deltamethrin--OMS 0.025%). All the five species were found susceptible to malathion. C. tritaeniorhynchus was resistant to DDT, dieldrin and fenitrothion; C. vishnui was also susceptible to fenitrothion and propoxur; C. pseudovishnui was resistant to dieldrin but it was susceptible to fenitrothion and propoxur. C. gelidus and C. fuscocephala were susceptible to dieldrin, fenitrothion and propoxur. Deltamethrin did not exhibit a good adulticidal effect except for C. pseudovishnui and C. fuscocephala. However, verifications are required to determine the susceptibility status of C. vishnui, C. pseudovishnui, C. gelidus and C. fuscocephala against DDT, C. tritaeniorhynchus against propoxur and C. vishnui against dieldrin.

Long term effects of smoke inhalation in survivors of the King's Cross underground station fire.

BACKGROUND: In most accidents causing smoke inhalation only a few victims actually inhale the smoke. The fire at King's Cross provided an opportunity to assess the long term effects of smoke inhalation in a larger number of patients. METHODS: Fourteen survivors from the King's Cross underground station fire were assessed for respiratory disability six months after the disaster and 10 were reassessed at two years. All had inhaled substantial quantities of smoke and 10 had skin burns of differing severity. RESULTS: Six months after the fire nine survivors admitted to one or more symptoms, which included hoarseness (two cases), cough (five cases), and breathlessness (six cases); and a survivor with asthma noted a worsening of his symptoms. The remaining five denied new symptoms. Peak expiratory flow, spirometric indices, and transfer factor for carbon monoxide were within the predicted normal ranges. The mean residual volume, however, was greater than the predicted value and the mean maximum expiratory flow at 25% of vital capacity (V25) less than predicted, with no significant differences between smokers (n = 7) and non-smokers (n = 7). At least one of these ventilatory defects, suggesting small airways obstruction, was present in 11 survivors at six months and they had persisted in the seven patients who were reassessed at two years. CONCLUSION: Smoke inhalation may be associated with injury to the small airways.

Carboxyhaemoglobin concentrations, pulse oximetry and arterial blood-gas tensions during jet ventilation for Nd-YAG laser bronchoscopy.

Oxygen saturation measured with pulse oximetry (SpO2) is overestimated in the presence of carboxyhaemoglobin (COHb). Smoke produced during laser resection of tracheobronchial malignancies may increase concentrations of COHb. We have measured COHb concentrations in 14 patients undergoing laser resection and compared SpO2 with functional oxygen saturation (SaO2) to ascertain if pulse oximetry is an accurate monitor of oxygen saturation. During the procedure frequent changes occur in ventilatory mechanics. Arterial blood-gas tensions were measured to see if gas exchange was satisfactory. Mean preoperative COHb was 1.4%. There was no significant change in COHb in any patient at any stage during treatment. The highest value was 2.05%. The mean difference between SaO2 and SpO2 was 1.13% (95% confidence interval 0.70-1.56%). Oxygen saturation may therefore safely be monitored by pulse oximetry in patients managed by our technique. Empirical setting of a jet ventilator provided acceptable blood-gas tensions, although sometimes it was necessary to increase the FlO2 to greater than 0.3 to maintain oxygenation.

Bronchography in the assessment of patients with lung collapse for endoscopic laser therapy.

In an attempt to improve selection of patients and the efficacy of endoscopic laser treatment, a bronchographic technique has been developed for patients with tumours causing complete endobronchial obstruction. This technique has shown patent distal airways in 16 out of 17 patients with a collapsed lung or lobe. These airways were abnormally dilated in each case, suggesting bronchiectasis. In one patient the appearances of bronchiectasis were sufficiently severe to decide against attempting treatment. Treatment was not attempted in another patient as a large cavity was seen within the collapsed lung and this was thought to carry a risk of postoperative infection and haemorrhage. Treatment with a neodymium YAG laser under general anaesthesia successfully recanalised the airway in 12 of the 15 remaining patients and was associated with a substantial reduction in breathlessness. The procedure was abandoned prematurely in one patient because of life threatening haemorrhage. In the remaining two patients in whom treatment was unsuccessful bronchography had suggested very extensive endobronchial obstruction. Spirometry and radionuclide lung scans were performed before and after treatment in eight patients treated successfully and showed significant improvements. Four patients were investigated within two weeks of lung re-expansion by repeat bronchography (three patients) or computed tomography (one patient); in each case the calibre of the airways had returned almost to normal. Thus the radiological demonstration of bronchial dilation in a collapsed lung does not necessarily imply a diagnosis of irreversible bronchiectasis and should not be regarded as a contraindication to treatment. It is concluded that preoperative bronchography provides reliable data on the extent of tumour, the patency of the distal airways, and presence of extensive cavitation. This information should facilitate successful laser treatment.

Elective resection of tumours of the trachea and main carina after endoscopic laser therapy.

In our patients with tumour affecting the trachea or carina elective surgery was carried out after endoscopic laser treatment. Laser treatment was performed as an emergency procedure in three of the patients, who presented with impending asphyxia; the improvement provided time in which to assess the disease, withdraw corticosteroids, and treat infection. The fourth patient was treated with the laser for life threatening haemoptysis, but further bleeding made it necessary to tamponade the tumour with a cuffed endotracheal tube for 24 hours. Elective resections of the trachea (three cases) and carina (one case) were performed successfully four to eight weeks after laser treatment. Frozen sections of the resection margins were clear in all cases and paraffin sections subsequently confirmed the localised nature of the lesions. All patients are alive and well with no evidence of tumour recurrence after 18 months to 4 years. Laser therapy appears to be an ideal preoperative treatment for patients with impending asphyxia but it may be of limited value in controlling very brisk haemorrhage.

Changes in regional ventilation and perfusion of the lung after endoscopic laser treatment.

To determine whether endoscopic laser treatment improves both ventilation and perfusion in patients with advanced lung cancer, krypton-81m ventilation and technetium-99m labelled macro-aggregate perfusion scanning was performed immediately before and two or four days after treatment in a consecutive series of 28 patients. Twelve patients had not received any other treatment before laser therapy and 16 had undergone previous treatments that included radiotherapy. Ventilation and perfusion were quantified by expressing the number of counts in the affected lung as a percentage of the total counts. Ventilation and perfusion improved after laser treatment in 23 patients (82%). The mean ventilation score in the affected lung rose by 50% (p less than 0.001) and the mean perfusion score rose by 24% (p less than 0.001). Incremental changes in ventilation and perfusion scores were positively correlated (r = 0.80). Mean spirometric values, six minute walking distance, the Karnofsky performance index, and breathlessness and wellbeing scores also improved significantly. Patients with main bronchial obstruction who had had no radiotherapy showed the most striking improvements. It is concluded that the removal of intraluminal tumour from the bronchial tree leads to matched improvements in ventilation and perfusion in most patients and that this is associated with valuable improvement in symptoms.

Covered expandable metal stent for recurrent tracheal obstruction.

Rapidly recurrent symptoms of airways obstruction by tumour may require repeated radiotherapy or endoscopic laser treatment--but these procedures may themselves be distressing. Use of a novel coated metal stent may reduce the frequency with which such palliative intervention is required.

Reversible cold lesions of the parahippocampal gyrus in monkeys result in deficits on the delayed match-to-sample and other visual tasks.

Two bilateral cooling probes were placed over the parahippocampal gyrus (pg) and the cortex just dorsolateral to it, the posterior inferotemporal gyrus (p.itg) in 4 Macaca fascicularis. Behavioral tests included: delayed match-to-sample (DMS); the acquisition and retention of single visual discriminations; the acquisition and retention of a concurrent visual discrimination task; and the retention of a spatial reversal task. During cooling of the pg and of the pg and p.itg together, there was a deficit at all delays on DMS. For both the single and concurrent visual discriminations, pg cooling produced an acquisition but not a retention deficit, although the acquisition deficit for the concurrent task was not significant at the 0.05 level. Cooling of p.itg had no significant effect on these tasks. No cooling had any affect on the spatial reversal task. It was concluded that pg serves as an important visual input into the anterior half of the itg for performance of DMS and the acquisition of visual discriminations. For several reasons, it was argued that the deficits were not caused by cooling of the hippocampus.