Effect of diarrhoea on Tacrolimus trough level in a post liver transplant patient.

Tacrolimus, which bonds to an immunophilin, FK506 binding protein (FKBP) has emerged as one of the most widely used immunosuppressant post solid organ transplantation. It offers excellent patient survival rates post-transplantation and a lesser number of acute rejections as compared to cyclosporine. Tacrolimus has a narrow therapeutic window with overexposure leading to acute and chronic forms of nephrotoxicity. Remarkably few data have been published on the overexposure to tacrolimus following mild diarrhoea in post-transplant patients who received treatment with tacrolimus. We observed a post-liver transplant patient with increased trough level of tacrolimus during severe diarrhoea with no complications following a timely adjustment on the dose of tacrolimus.

Cholangiocarcinoma: a 10-year experience of a single tertiary centre in the multi ethnicity-Malaysia.

Cholangiocarcinoma (CCA) is a rare biliary tract epithelial malignancy. We described the clinical features of CCA patients in our institution. A 10-year retrospective study of patients with cholangiocarcinoma in University Malaya Medical Centre was conducted. Clinical data and outcomes in relation to the three anatomical groups of CCA were collected and analysed. Of the 69 patients that were included 55% were male. Mean age was 61 years. Twelve (17%) had intrahepatic, 38 (55%) perihilar and 19 (28%) distal tumour. Mean age (p=0.043), median duration of symptoms (p=0.011), jaundice (p<0.001), total bilirubin level (p=0.003), INR (p=0.005) and mean tumour size (p=0.048) were significantly related to the site of tumour. Only 12 patients had curative resection with seven R0 resections. Cholangiocarcinoma is increasingly diagnosed in our population. Despite that, the diagnosis is still often late. Age, jaundice and tumour size may predict anatomical location of CCA.

Dyspnea response following bilateral thoracoscopic staple lung volume reduction surgery.

PURPOSE: Lung volume reduction surgery (LVRS) has shown promise for treating patients with severe emphysema in recent clinical trials. However, response following surgery is difficult to assess due to frequent discrepancies between subjective and objective outcomes. We evaluated the relationship between improvement in dyspnea and pulmonary function response in 145 consecutive patients with inhomogeneous emphysema enrolled in a bilateral thoracoscopic lung volume reduction protocol in order to assess predictors of improved dyspnea outcome and correlation of subjective and objective improvement measures. MATERIALS AND METHODS: Baseline complete pulmonary function testing, spirometry, gas exchange, plethysmography, gas dilution lung volumes, along with resting dyspnea index determinations were performed preoperatively, and repeated short term (mean, 33 days; n=129) and long term (>6 months; mean, 276 days; n=84) following surgery. RESULTS: Improvement in FEV1 percent predicted was significantly associated with improvement in dyspnea scores, though considerable variability exists (r=0.04, p<0.01, short term; r=0.4, p=0.1, long term). In this preselected patient group, those with the extreme degrees of hyperinflation may have less improvement in dyspnea following LVRS than those with milder preoperative hyperinflation. Greater improvement in dyspnea short term and long term was seen in patients with lower presenting residual volume/total lung capacity ratios (r=0.4, p=0.02, short term; r=0.4, p<0.05, long term). CONCLUSIONS: Bilateral thoracoscopic staple LVRS results in significant objective and subjective improvement in patients with severe emphysema and hyperinflation. There was considerable variability between improvement in dyspnea and improvement in spirometry, and preoperative predictors of response may differ between these outcome variables. Further studies are needed to define the long-term implications of these findings.

Patient selection criteria for lung volume reduction surgery.

OBJECTIVE: Our intent was to refine the patient selection criteria for lung volume reduction surgery because various centers have different criteria and not all patients benefit from the procedure. METHODS: Patient information, x-ray results, arterial blood gases, and plethysmographic pulmonary function tests in 154 consecutive patients who underwent bilateral thoracoscopic staple lung volume reduction surgery were compared with clinical outcome (change in forced expiratory volume in 1 second and dyspnea scale) with t tests and analysis of variance. RESULTS: Three hundred thirty-three of 487 (69%) patients evaluated for lung volume reduction surgery were rejected for lack of heterogeneous emphysema (n = 212), medical contraindications (n = 88), hypercapnia (n = 20), uncontrolled anxiety or depression (n = 10), or pulmonary hypertension (n = 1). Two patients died during the evaluation process. When tested by analysis of variance, there was no difference in clinical outcome associated with preoperative forced expiratory volume in 1 second, residual volume, total lung capacity, single-breath diffusing, and arterial oxygen or carbon dioxide tension. All patients selected for the operation had a heterogeneous pattern of emphysema. The upper lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan was strongly associated with improved outcome with a mean (95% confidence interval) improvement in forced expiratory volume in 1 second of 73.2% (63.3 to 83.1) for the upper lobe compared with a mean (95% confidence interval) improvement of 37.9% (22.9 to 53.0) for the lower lobe or diffuse pattern of emphysema. CONCLUSION: The most important selection criteria for lung volume reduction surgery is the presence of a bilateral upper lobe heterogeneous pattern of emphysema on chest computed tomography and lung perfusion scan. After patients have been selected on the basis of a heterogeneous pattern of emphysema, clinical factors and physiology are not associated with clinical outcome well enough to further refine patient selection criteria. These results do not support the arbitrary patient selection criteria for lung volume reduction surgery reported in the literature.

Changes in pulmonary physiology after lung volume reduction surgery in a rabbit model of emphysema.

OBJECTIVE: The purpose of this study is to investigate the effects of lung volume reduction surgery on pulmonary compliance, airway flow, and helium lung volumes in an elastase-induced emphysema animal model. METHODS: A 15,000-unit bolus of elastase was aerosolized through an endotracheal tube in 14 New Zealand White rabbits to induce emphysema. Stapled lung volume reduction of bilateral upper and middle lobes was performed through a midline sternotomy at 4 weeks after induction of emphysema. Lung functions were measured at baseline before induction of emphysema, preoperatively at 4 weeks, and 1 week postoperatively. RESULTS: Compliance increased after induction of emphysema and decreased in response to lung volume reduction surgery. Functional residual capacity decreased after lung volume reduction surgery in proportion to the amount of excised lung tissue. Expired flows suggested improvement in response to lung volume reduction surgery. Histologic examination confirmed presence of diffuse heterogeneous emphysema in each animal at necropsy. CONCLUSIONS: The decreased compliance and increased airway flow after volume reduction surgery in this model parallels findings in human studies and suggests that similar mechanisms of increased elastic recoil and airway support contribute to improvement.

Factors related to outcome in blunt intestinal injuries requiring operation.

Associated factors related to outcome following blunt intestinal trauma requiring operative therapy were retrospectively reviewed in all trauma patients admitted to one Level I trauma center. Over 4.5 years, 7598 trauma patients were evaluated, with 62 patients having sustained 92 blunt intestinal injuries requiring operative intervention. Mean age was 34.5 years; mean Injury Severity Score was 22. Mechanism of injury was motor vehicle accident in 50 (81%), with 80 per cent being drivers. Associated intra-abdominal injuries occurred in 46 (74%) patients. Extra-abdominal injuries occurred in 56 patients (90%). Thirty-one patients suffered 82 complications or 2.6 complications per patient (comp/pt). Mortality from operative blunt trauma was associated with admission blood pressure < or = 90 mm Hg (57 vs 13%; P < 0.05), age > or = 24 years (26 vs 0%; P < 0.05), and Injury Severity Score > or = 35 (70 vs 8%; P < 0.05). Morbidity was associated with age > or = 24 years (1.5 vs 0.7 comp/pt; P < 0.05) and delay in operative therapy > or = 24 hours (3.3 vs 1.1 comp/pt; P < 0.05). Overall mortality was 18 per cent.

Effect of lung volume reduction surgery in a rabbit model of bullous lung disease.

Clinical use of staple lung volume reduction surgery (LVRS) has proliferated for treatment of emphysema despite limited data regarding efficacy or optimal techniques. Recent studies in animal models of obstructive lung disease describe the decrease in lung compliance and increase in airway support as mechanisms of an improvement in pulmonary functions analogous to human data. We describe contrasting results in an animal model of bullous lung disease with a mixed but predominantly restrictive pattern of lung disease. Mixed restrictive and bullous lung disease was induced in 17 New Zealand white rabbits with i.v. Sephadex beads and endotracheally instilled carrageenan. Unilateral stapled lung volume reduction surgery was performed at 5 weeks postinduction of emphysema on the right lower lobe by lateral thoracotomy using a pediatric stapler. Static trans-pleural pressures were measured at 60, 40, and 20 cm3 inflation at preinduction (baseline), pre- and postoperatively, and 1 week postoperatively in anesthetized animals. Lungs were then harvested en bloc and examined histopathologically. The effects of volume reduction surgery on static lung compliance, lung conductance, and forced expiratory flows (FEF) were assessed. Five weeks after induction of lung disease, the animals had no significant change in static compliance and forced expiratory volume in 0.5 s (FEV0.5) or lung conductance compared to baseline. Immediately following LVRS, the animals showed a significant decrease in static compliance, FEV0.5, and conductance. One week postoperatively, compliance increased to approximately baseline levels along with a slight increase in FEFs and conductance toward preoperative levels. Histology examination revealed restrictive and bullous lung disease. Thus, we have demonstrated the feasibility of using an animal model for evaluation of volume reduction therapy for restrictive-obstructive lung disease. Physiologically, this model showed decrease conductance and decreased forced expiratory flows following lung volume reduction despite increased recoil. This is in contrast to increased conductance and flows seen in humans with severe emphysema following surgery and suggests that current criteria excluding patients with a significant restrictive component to their lung disease from LVRS surgery may be justified.

An animal model for lung volume reduction therapy of pulmonary emphysema.

Stapled lung volume reduction surgery (LVRS) has recently been described for treatment of emphysema. Many questions arise regarding physiologic mechanisms of response from surgical treatment of emphysema. The objective of this study was to develop an animal model for the study of lung volume reduction surgery in diffuse heterogeneous emphysema. We hypothesized that elastic recoil would increase, static respiratory system compliance would decrease, and expiratory flows would increase after lung volume reduction surgery in animals with emphysema. In the study, emphysema was induced in 31 New Zealand White rabbits (3-5 kg) with endotracheally aerosalized porcine elastase (10,000-12,000 U). Lateral thoracotomies were performed 4-6 weeks postinduction under general anesthesia and mechanical ventilatory support. Stapled volume reduction was performed on the right lower lobe using a standard multirow pediatric stapler (U.S. Surgical). Pulmonary function tests were performed at baseline (preinduction), before stapling LVRS (postemphysema induction), immediately post stapling LVRS, and 1 week poststapling. Static respiratory system compliance, flow, conductance and forced expiratory flows, and peak flows at 20 and 40 cm3 of exhaled volume were analyzed. Animals were sacrificed 1 week poststapling, and bilateral lungs were harvested for histopathology. Diffuse but heterogeneous pulmonary emphysema was seen in these animals treated with high-dose aerosolized elastase. Static compliance increased, while expiratory flows and conductance decreased after induction of emphysema. Immediately post stapled volume reduction therapy, animals had decreased static compliance. By 1 week following surgery, animals showed increased forced expiratory flows and decreased expiratory resistance, although compliance was similar to preoperative levels. In conclusion, we describe initial results in an animal model of obstructive emphysema suitable for the study of lung volume reduction surgery. Changes in pulmonary function indicate that unilateral lower lobe LVRS increases airway conductance in the rabbits. Findings from LVRS studies in animal models such as this may help explain clinical improvement following LVRS in humans.

Predictors of axillary lymph node metastases in breast cancer: is there a role for minimal axillary surgery?

INTRODUCTION: Axillary nodal status is one of the most important prognostic factors in breast cancer. In the present study we used it to determine the predictors of axillary lymph node metastases in breast cancer and to determine if there is a group of patients in whom minimal axillary surgery is indicated. METHODS: This article reports a retrospective study of 953 patients with T1 and T2 invasive breast carcinomas seen in the University Malaya Medical Centre between January 2001 and December 2005, where axillary dissection was done. RESULTS: Of the 953 patients, 283 (29.7%) had breast-conserving surgery, and the rest had mastectomies. In this series, 463 patients (48.6%) were younger than 50 years of age; 365 patients (38.3%) had lymph node involvement. The Malays tend to have more axillary node metastases (45.1%) than the Chinese (36.9%); however, there was no significant relationship between age and race and lymph node involvement. Some 23.9% of grade 1 cancers were node positive, compared to 42.9% of grade 2/3 cancers. Tumor size ranged from 0.2 cm to 5 cm; 55.5% of tumors were T2 (>2-5 cm). There were only 13 (1.4%) T1a tumors (>0.1-0.5 cm). Node involvement was documented in 7.7% of T1a tumors, 12.3% of T1b tumors (>0.5-1 cm), 29.2% of T1c tumors, and 48.2% of T2 tumors. In patients who had no lymphovascular invasion (LVI), 24.4% had axillary node metastases, compared with 52.2% of patients where LVI was reported. On univariate analysis, our study found that tumor diameter>2 cm, presence of lymphovascular invasion, and higher tumor grade (2&3) were factors significantly associated with a higher risk of nodal metastases. On multivariate analysis, however, only lymphovascular invasion and tumor size were independent predictors based on the logistic regression. CONCLUSIONS: In T1 tumors, axillary lymph node dissection will overtreat almost 75% of cases; therefore a sentinel lymph node biopsy is justified in these tumors. Sentinel lymph node biopsy has been shown to reduce the complications of formal axillary dissection, such as shoulder stiffness, pain, and lymphedema. In patients with T2 tumors, where almost 45% have lymph node involvement, sentinel node biopsy may not be cost effective.

Does the pre-operative value of serum CA15-3 correlate with survival in breast cancer?

INTRODUCTION: CA15-3 is a well-known tumour marker for breast cancer. Currently it is not recommended for screening or diagnosis of breast cancer and its main application is in monitoring response to treatment in women with metastatic breast cancer. The aim of this study was to correlate serum CA15-3 at presentation with the stage of disease and overall survival in women with breast cancer in the University Malaya Medical Centre. METHODS: This is a retrospective study of 437 women who had CA15-3 levels determined at initial presentation of breast cancer to UMMC between Jan 1999 and Oct 2003. RESULTS: Of those patients who were adequately staged, CA15-3 was found to be elevated (defined as >51 U/ml) in 0% of Stage 1, 7.9% of Stage 2, 36.7% of Stage 3 and 68.6% of Stage 4 cases. In a subset of 331 patients with survival data, patients with normal CA15-3 had a 85% five year overall survival rate compared to 38% in their counterparts with elevation of the tumor marker. The level of elevation was also significantly related to survival; patients with values more than 200 U/ml exhibited only a 28% five year survival. The association of elevated CA15-3 at initial presentation with poor outcome was maintained over univariate and multivariate analyses. CONCLUSION: Estimation of CA15-3 at presentation of breast cancer is important as it is an independent prognostic indicator and may prompt the physician to investigate for metastases if elevated.

Effect of lung volume reduction surgery on pulmonary diffusion capacity in a rabbit model of emphysema.

BACKGROUND: While there is renewed interest in lung volume reduction surgery (LVRS) for treatment of emphysema, many aspects of the operation such as patient selection and surgical end points of excision are uncertain. We studied the effects of LVRS on measured lung volumes and diffusion capacity in an animal model to investigate optimal resection volumes. METHODS: Emphysema was induced in 32 New Zealand white (NZW) rabbits using aerosolized elastase. Helium dilution lung volumes and single breath DLCO were measured concurrently at baseline, following induction of emphysema (preop), and 1 week postoperatively (postop) following LVRS. Bilateral upper and middle lobe stapled lung resections were performed through midline sternotomies with excision of variable amounts of lung tissue from 1.8 to 5.8 g. RESULTS: FRC increased following induction of emphysema and decreased postoperatively. DLCO improved with increasing lung tissue resection up to 3 g of tissue and then decreased as even greater amounts were removed (r = 0.54). CONCLUSIONS: Measured lung volumes increase with development of emphysema and appropriately decrease in response to LVRS in this rabbit model. DLCO improves with moderate resection but then decreases with excessive excision of lung quantities and may help define one physiologic operative end point. In this rabbit model, excision of approximately 30% of lung volume was optimal and prevented further decrease in diffusion capacity.

Comparison of Ho:YAG versus Nd:YAG thoracoscopic laser treatment of pulmonary bullae in a rabbit model.

OBJECTIVE: To determine the relative efficacy and morbidity of Ho:YAG versus Nd:YAG laser treatment of bullous lung disease in an animal model. SUMMARY BACKGROUND DATA: Laser coagulation procedures for treatment of emphysematous pulmonary bullae and heterogeneous emphysema continue to evolve. The role of lasers in lung volume reduction surgery remains controversial due to issues of relative efficacy and morbidity. The Nd:YAG laser is most commonly used for these procedures. We hypothesized that the shallower penetration of the Ho:YAG laser may be better suited for laser bullae coagulation and emphysema lung volume reduction with increased efficacy and reduced lung injury. METHODS: Thirty New Zealand White rabbits (15 normal rabbits; 15 with bullous lung disease) were evaluated with Ho:YAG compared to Nd:YAG laser exposures. Bullae were coagulated by either Ho:YAG or Nd:YAG treatment. In all animals (bullous-induced and normals), unaffected lung tissue in the upper lobes and contralateral lungs were treated with 5 spot exposures of Nd:YAG and Ho:YAG, each to assess depth of lung injury. Animals were sacrificed at Days 0, 7, and 21 and their lungs were examined histologically. RESULTS: Ho:YAG and Nd:YAG exposures caused equivalent lung injury to normal lung tissue. In the acute phase, parenchymal necrosis depth was similar for both Ho:YAG and Nd:YAG (850 +/- 273 microns vs. 900 +/- 270 microns respectively, p = 0.7). By Day 7, lung necrosis depth was 925 +/- 133 microns Ho:YAG vs. 1225 +/- 235 microns Nd:YAG (p = 0.33), and lung fibrosis depth was 300 +/- 134 microns Ho:YAG vs. 558 +/- 127 microns Nd:YAG (p = 0.11). By Day 21, pulmonary parenchymal necrosis was not seen. Pleural fibrosis depth was maximal at Day 21, reaching 250 +/- 102 microns for Ho:YAG vs. 300 +/- 156 microns Nd:YAG (P = 0.88). Pleural necrosis depth was 67 +/- 42 microns Ho:YAG vs 48 +/- 34 microns Nd:YAG (p = 0.42) on Day 7 and resolved by Day 21. During surgical coagulation procedures, the Ho:YAG laser was dramatically more efficient in coagulating bullae. The Ho:YAG laser required less exposure at equivalent power and resulted in immediate desiccation of bullae, in sharp contrast to the Nd:YAG laser. CONCLUSIONS: Because the Ho:YAG was more effective and did not result in more acute lung injury than the standard Nd:YAG laser in this study, Ho:YAG lasers may have improved potential for laser treatment of bullae or lung volume reduction surgery (LVRS) compared to Nd:YAG lasers.