Pulmonary histiocytosis X in a patient with epithelioid mesothelioma.
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Biomedical subjects
Publications and source records attributed to W S Walker.
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Accurate staging of the mediastinum in lung cancer is essential for optimising treatment strategies. Conventional transbronchial needle aspiration (TBNA) is a blind procedure, reliant upon prior computed tomography (CT) or ultrasound imaging, but has low sensitivity. The current study reports the initial experience of using a prototype endobronchial ultrasound (EBUS) probe that allows TBNA under real-time imaging. In 20 patients selected by CT scanning, a linear-array ultrasound bronchoscope was used to visualise paratracheal and hilar lymph nodes, and TBNA was performed under direct ultrasonic control. In seven cases, sequential endoscopic ultrasound (EUS) was used to assess postero-inferior mediastinal lymph nodes. All procedures were performed under conscious sedation. EBUS-TBNA was undertaken in 18 out of 20 cases and EUS-guided fine-needle aspiration in six out of seven cases. Cytology showed node (N)2/N3 disease in 11 out of 18 EBUS-TBNA cases and provided a primary diagnosis for eight patients. EBUS-TBNA cytology was negative in six cases, which was confirmed by mediastinoscopy or clinical follow-up in four. EUS provided additional information in all cases. There were no procedural complications. Sensitivity, specificity and accuracy for EBUS-TBNA were 85%, 100% and 89%, respectively. In conclusion, endobronchial ultrasound with real-time transbronchial needle aspiration offers improved sensitivity and accuracy for staging of the middle mediastinum, and, combined with endoscopic ultrasound, should allow investigation of the majority of the mediastinum.
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OBJECTIVE: Repeat median sternotomy is a potentially dangerous technique providing variable but mainly poor access to the mitral valve. Right thoracotomy is an alternative route previously used to access the mitral valve in the early years of cardiac surgery that offers the advantage of a fresh surgical field in the context of redo surgery. We have reviewed our experience with mitral prosthetic replacement undertaken via a right thoracotomy in order to determine the immediate and long-term results obtained with this approach. METHODS: The operation was carried out on a beating heart using normothermic bypass without cross-clamping the aorta. Arterial inflow was achieved via the femoral artery or ascending aorta and venous drainage with bi-caval cannulae. Pre-, intra- and postoperative data were documented from case note review. Long-term follow-up was established from the UK Heart Valve Registry, referring Cardiologist, direct patient contact and the Scottish Registry for births and deaths. Statistical analysis was undertaken using a desktop computer package. RESULTS: One hundred and twenty-five patients (mean age 63 years) underwent mitral prosthetic replacement by this technique. One hundred and eleven patients (86%) were in NYHA grades III or IV preoperatively. Twenty-two patients (16.6%) had also undergone previous CABG. Thirty-five patients (28%) had undergone two or more sternotomies. Mean bypass time was 83.6 min (SD 43.1). Postoperatively, mean duration of ventilation was 44 h; mean ITU stay was 4 days (SD 5.3) and mean inpatient total stay was 12 days. Thirty-six patients (28.8%) required inotropic support postoperatively. Complication rates were low: pleuro-pulmonary, 30 patients (24%), re-operation for bleeding, four patients (3.2%) and CVA, two patients (1.6%). Eight patients (6.4%) died within 30 days. Ten-year survival figures (Kaplan-Meier) were: 47% for all causes of mortality and 82.9% when only valve related causes of death were considered. Most of the patients (97.5%) had not required re-operation at 10 years. CONCLUSION: Mitral prosthetic replacement via a right thoracotomy on beating heart under normothermic bypass offers a safe alternative to redo median sternotomy in this high-risk group. Operative access is facilitated and procedural time reduced. Complication rates are low and perioperative mortality is lower than that generally reported with conventional surgery.
OBJECTIVE: Sequential lung volume reduction (LVR) is thought to provide additional and prolonged benefit compared with unilateral LVR. We tested this hypothesis by reviewing physiological, subjective and survival outcome data on patients who underwent sequential or unilateral LVR. METHODS: LVR was performed as a unilateral video-assisted thoracoscopic surgery (VATS) procedure, with bilateral reduction being undertaken in a staged manner. Pulmonary function data were collected prospectively. A telephone survey of patients and general practitioners was used to determine quality of life and survival. RESULTS: Fifty patients underwent LVR. Twenty-one patients had staged reduction of the contra-lateral lung at a median interval of 9 months. Pre-operatively, patients undergoing sequential LVR were not significantly different from patients undergoing unilateral LVR: forced expiratory volume in 1 s (FEV1) 23% predicted vs. 27% predicted, KCO 40% vs. 45%, total lung capacity (TLC) 124% vs. 121%, residual volume (RV) 217% vs. 214%, health score 34.5 vs. 30.8. After single-side LVR, both groups demonstrated equivalent and significant improvement in spirometric and subjective health scores: FEV1 +15% predicted (P<0.01), TLC -5% (P=0.03), health score +80% (P<0.01). Patients undergoing sequential reduction demonstrated no further significant improvements using either an intragroup comparison with their pre-second operation values or an intergroup comparison with the unilateral LVR patients. However, sequential LVR appeared to prolong the benefits experienced after the initial surgery by 1 year. Overall, 12 patients (24%) died during follow-up with no survival difference between the two groups (P=0.65). CONCLUSION: Sequential LVR is a safe strategy. Undertaking LVR to the second side does not further improve spirometric or subjective performance but does prolong the benefits achieved with the initial reduction.
OBJECTIVES: Ideal treatment for achalasia permanently eliminates the dysfunctional lower oesophageal sphincter, relieving dysphagia and regurgitation. The aim of this study was to review the results in a series of patients undergoing video-imaged thoracoscopic Heller's myotomy (THM). METHODS: Records of all patients undergoing THM by a single surgeon at one institution were analysed. Follow-up was conducted using a structured questionnaire together with oesophageal manometry and/or 24 h pH monitoring when clinically indicated. RESULTS: Twenty-five consecutive patients (13 males, 12 females, mean age 40.3+/-19.9 years) suffering from grade 4 dysphagia underwent THM between 1993 and 2001. Preoperative mean lower oesophageal sphincter (LOS) pressure was 42.6+/-6.3 mmHg. Seven patients (28%) had undergone previous pneumatic dilatations. There were no hospital deaths and no oesophageal perforations. Length of hospital stay was 4.3+/-1.8 days. One patient died 3 years after surgery from unrelated causes. At follow-up of 5.4+/-2.1 years, freedom from any reintervention was 95.8% (23/24). Eleven patients (45.8%) were asymptomatic. In patients with residual or recurrent symptoms (n=13), their severity was significantly reduced from the preoperative period (dysphagia score 1.7+/-0.8 versus 4+/-0; P</=0.05). Four patients (16%) with troublesome residual or recurrent grade 3-4 dysphagia underwent repeat oesophageal manometric study, showing a mean reduction in LOS pressure from their baseline values of 46.8+/-6.1 to 30+/-5.4 mmHg (P</=0.01). One of these patients (4.2%) required repeat Heller's myotomy 1.5 years after THM. Six patients complained of troublesome postoperative heartburn; distal oesophageal acid exposure was shown to be abnormal in 3 (12.5%) of these patients and all enjoyed symptomatic relief with medical therapy. CONCLUSIONS: THM is a safe and effective procedure in the treatment of achalasia. Some patients do experience recurrence of symptoms; however, these are significantly less severe. The incidence of postoperative heartburn is acceptably low and can be controlled with oral medications, making the addition of an anti-reflux procedure not necessary. Longer-term follow up and randomised studies comparing THM to other therapeutic modalities are needed to ascertain respectively the durability of this approach and its relative advantages.
OBJECTIVE: A free jejunal graft is used for reconstruction following pharyngolaryngooesophagectomy, due to the relative ease of harvesting, low donor site morbidity and a lumen diameter compatible with that of the oesophagus. Our aim is to evaluate the postoperative outcome and functional results of the procedure. METHODS: Retrospective analysis of 20 consecutive patients, with a mean age of 62.5 years (range 48--76), who underwent free jejunal reconstruction following pharyngolaryngooesophagectomy for laryngeal malignancy. Surgery was performed secondary to radiotherapy or as the main stem of treatment. The functional results were assessed at 6 months and 1 year and correlated with postoperative morbidity. Chi-square test was used for statistical significance and Kaplan--Meyer to estimate survival. RESULTS: There were six transient leaks and six cases with anastomotic stricture. There was no morbidity associated with the donor site and the perioperative mortality (30 days) was zero. At 6 months, 13 (87%) out of the 15 patients alive had satisfactory speech and 11 (78%) had satisfactory swallowing. At 1 year, 11 patients were alive and maintained a satisfactory speech, while nine (81%) of them were eating well. The incidence of leaks, strictures, or the moment of radiotherapy has no influence on the functional outcome. The 1- and 3-year survival rates were 52.3 and 33.2%, respectively. CONCLUSIONS: A free jejunal graft reconstruction is technically demanding, but provides a near-physiologic swallowing mechanism, avoiding the complications of a gastric pull-up procedure. Functional results are good and justify the procedure despite the relatively high co-morbidity.
OBJECTIVES: Major thoracic surgery is associated with trauma-related immunological changes. These may impair anti-tumour immunity. We hypothesize that the reduced operative trauma associated with a video-assisted thoracic surgery (VATS) approach may decrease acute phase responses and, consequently, lead to better preservation of immune function. This prospective randomized study compared the effects of conventional open thoracic surgery and VATS on acute phase responses in patients undergoing pulmonary lobectomy. METHODS: Acute phase indicators were analyzed in patients undergoing lobectomy for suspected bronchogenic carcinoma. Surgery was prospectively randomized to pulmonary lobectomy by VATS or limited postero-lateral thoracotomy. Blood was taken pre-operatively and at 4, 24, 48, 72, 120 and 168 h post-operatively for analysis of C-reactive protein (CRP; 41 patients: open, n=22; VATS, n=19) interleukin (IL)-6, tumour necrosis factor (TNF) receptors (TNF-sR55, TNF-sR75) and P-selectin (24 patients: open, n=12; VATS, n=12). Samples taken at 48 and 168 h were also analyzed for phagocyte reactive oxygen species (ROS) production (25 patients: open, n=16; VATS, n=19). RESULTS: Surgery increased acute phase responses. VATS was associated with lower CRP and IL-6 levels. In the open surgery group, significant increases in ROS in neutrophils (up to 36% greater than before surgery, n=12, P<0.02-0.05) were detected at 2 days after surgery, but in the VATS group, the increase after surgery (of up to 17%, n=18) did not reach significance. Similarly, monocyte ROS increases of up to 25% in the mean ROS in the open surgery group and of up to 17% in the VATS group were detected on days 2 and 7 after surgery. CONCLUSIONS: VATS pulmonary lobectomy is associated with reduced peri-operative changes in acute phase responses. This finding may have implications for peri-operative tumour immuno-surveillance in lung cancer patients.
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Primary pericardial Hodgkin's disease is extremely rare, increasingly so in the decades of modern imaging. We illustrate one of these atypical presentations, with absent mediastinal lymphadenectomy and with pericardial effusion successfully managed by video-assisted thorascopic surgery (VATS).
BACKGROUND: Immunosuppression associated with surgery may predispose to increased tumour growth or recurrence. Lymphocytes are central components of the immune network, signalling specific and non-specific responses in tumour immunosurveillance. This study was therefore designed to compare the effects of minimally invasive and conventional approaches to major thoracic surgery on lymphocyte populations and oxidative activity. PATIENTS AND METHODS: The effects of conventional and minimally invasive video-assisted thoracic surgery (VATS) on the numbers and types of circulating lymphocytes and on lymphocyte oxidation were compared in a prospective randomized study of 41 patients undergoing lobectomy for peripheral bronchogenic carcinoma. Blood taken pre-operatively and on days 2 and 7 post-operatively was analysed for T (CD4, CD8), B (CD19) and natural killer (NK) (CD56, CD16) cell counts and for lymphocyte oxidative activity. Leucocyte numbers were compared with pre-surgical values and oxidative rate with healthy donor controls. RESULTS: Lymphocyte counts fell after surgery; VATS was associated with less effect on circulating T (CD4) cells at 2 days and on NK lymphocytes at 7 days post-surgery. Lymphocyte oxidation was less suppressed in the VATS group 2 days after surgery. In general, post-surgical changes in key cells of cellular immunity were smaller in the VATS group, and recovery to normal levels was more rapid. CONCLUSION: The degree of invasiveness of thoracic surgery may influence the extent of immunosuppression in patients undergoing pulmonary lobectomy for pulmonary neoplasm.
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The brain contains two populations of macrophages: the microglia of brain parenchyma, and the central nervous system (CNS) macrophages located in the perivascular spaces, the leptomeninges and the choroid plexus. The microglia are characterized, in part, by their paucity of major histocompatibility complex (MHC) molecules and lack of constitutive antigen (Ag)-presenting activity for naïve CD4+ T-cells. Some CNS macrophages, on the other hand, constitutively express MHC molecules and present Ag to naïve CD4+ T-cells. We have reported that mouse brain contains precursor cells that, in the presence of colony-stimulating factor-1, the macrophage growth factor, give rise to clones of cells that differ in their ability to constitutively present Ag to naive CD4+ T cells. Here we report that this population of precursor cells can be separated into two discrete subpopulations based on differences in cell density and that the two cell populations give rise to progeny that differ in their content of cells constitutively expressing MHC class II and CD86 molecules, and the ability to present Ag to naïve CD4+ T-cells. A comparison of the level of CD45 staining of the progeny, an indication of a microglial or a CNS macrophage origin, suggests that one population of precursor cells yields immunologically immature microglia and the other CNS macrophages.
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Microglia are one of the major glial cell types within the central nervous system, and can function as immune effector cells upon activation. CD40 is a cell surface receptor belonging to the TNF receptor family that plays a critical role in the regulation of immune responses. In this study, we investigated the expression of CD40 on microglia, and the role of transforming growth factor-beta (TGF-beta), an immunosuppressive cytokine, in regulating CD40 expression. Microglia constitutively express very low levels of CD40, and IFN-gamma enhances CD40 mRNA and protein expression in these cells. IFN-gamma-induced CD40 mRNA expression is partially sensitive to the protein synthesis inhibitor puromycin, suggesting that ongoing protein synthesis is necessary for optimal induction of CD40 mRNA by IFN-gamma. TGF-beta inhibits IFN-gamma-induced CD40 protein and mRNA expression. Inhibition of IFN-gamma-induced CD40 mRNA levels by TGF-beta in microglia is not due to inhibition of CD40 transcription; rather, inhibition is due to enhanced degradation of CD40 mRNA. These results indicate that TGF-beta can inhibit expression of an immunologically important receptor, CD40, in microglia, and does so at the post-transcriptional level by destabilizing CD40 mRNA. TGF-beta inhibition of CD40 expression may be one of the mechanisms by which TGF-beta exerts its suppressive effects on immune responses.
In 6 patients undergoing prosthetic mitral valve replacement a ring of Teflon felt, instead of conventional Teflon pledgets, was used because of concern about seating a new prosthesis in a disrupted friable mitral valve annulus. The technique avoided the potential risk of pledget loss in the event of suture breakage and, in these patients, prevented postoperative paraprosthetic mitral valve regurgitation.
BACKGROUND: There is growing evidence that blood transfusion is associated with clinical factors that can lead to transfusion-induced immunosuppression. This effect can be beneficial or deleterious. METHODS: The effect of perioperative allogeneic blood transfusion on survival was studied retrospectively in 524 patients who were discharged from the hospital after esophagogastrectomy for carcinoma performed in a single unit over a 10-year period. RESULTS: The median operative blood loss for the series was 500 mL (range, 50 to 3,750 mL). Three hundred thirty-five patients (64%) received a perioperative allogeneic blood transfusion related to esophagogastrectomy, and 189 (36%) did not. The median perioperative blood transfusion administered was 900 mL (range, 300 to 12,950 mL). Perioperative allogeneic blood transfusion was associated with reduced survival for patients in stage III (p < 0.05) at 1 year, but no significant difference was found in this stage at 3 or 5 years after resection. Stage III disease accounted for 250 (48%) of the 524 patients discharged. CONCLUSIONS: Although perioperative allogeneic blood transfusion does not affect long-term survival after esophagogastrectomy for carcinoma, it does have a significant association with short-term survival in a group whose overall survival is often limited after resection. Attention should be directed toward minimizing operative blood loss and transfusing only for factors known to be clinically important, such as oxygen delivery and hemodynamics, not arbitrary hemoglobin levels.
One hundred fifty video-assisted thoracic surgery (VATS) endoscopic hilar dissection lobectomy procedures are presented. Median blood loss was 65 mL and correlated with operative time (P < .0001) which averaged 144 minutes. Conversion to open thoracotomy was required in a further 20 patients (11.8%). One VATS patient (0.67%) died at 4 days from a catastrophic pulmonary embolus and 2 patients died within 30 days of surgery from pulmonary embolism and adrenal failure (overall 30-day mortality, 2%). Serious complications occurred in 3 cases: bronchopleural fistula (1) and requirement for ventilation (2). Air leakage (>4 days) occurred in 17 patients, correlated (P < .0003) with the presence of either adhesions or fissural fusion (11.3%), and resulted in prolonged hospitalization compared with patients without air leakage (11.1 vs 6.7 days; P < .0004). Open thoracotomy patients required 42% more morphine (P < .001) and 25% more nerve blocks than VATS patients (P < .001) who were 33% more likely to sleep following surgery (P < 0.01). Follow-up of 97 patients with non-small cell lung cancer (2,634 months total: mean 27) revealed 14 recurrences: 10 systemic and 4 (28.6%) within the thorax. No port site or pleural recurrences occurred. Stage analysis showed survival free of lung cancer-related death of 94% at 36 months for Stage I, 57% for Stage II, and 25% for Stage III.