Kidney after nonrenal transplantation-the impact of alemtuzumab induction

BACKGROUND.: Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population. PATIENTS AND METHODS.: We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007. Seventy-two patients transplanted between January 15, 2003, and October 8, 2007, received alemtuzumab induction and continued their pretransplant immunosuppression. Seventy-two patients transplanted between May 18, 1998, and July 21, 2007, did not receive alemtuzumab induction, but received additional steroids and maintenance immunosuppression. Donor and recipient demographics were comparable. RESULTS.: Overall, 1-and 3-year patient survival and renal function were comparable between the two groups. One-and 3-year graft survival was 93.0% and 75.3% in the alemtuzumab group and 83.3% and 68.7% in the no alemtuzumab group, respectively (P=0.051). The incidence of acute rejection was lower in the alemtuzumab group, 15.3%, than in the no alemtuzumab group, 41.7% (P=0.0001). The incidence of delayed graft function was lower in the alemtuzumab group, 9.7%, than in the no alemtuzumab group, 25.0% (P=0.003). The incidence of viral complications was comparable. CONCLUSION.: Alemtuzumab induction with simple resumption of baseline immunosuppression in patients undergoing kidney transplantation after nonrenal transplantation represents a reasonable immunosuppressive strategy. Copyright © 2009 by Lippincott Williams & Wilkins

Pediatric lung transplantation: The years 1985 to 1992 and the clinical trial of FK 506

The application of lung transplantation to the pediatric population was a natural extension of the success realized in our adult transplantation program, which began in 1982. Twenty pediatric patients (age range 3 to 18 years) have had heart-lung (n = 11), double lung (n = 8), and single lung (n = 1) transplantation procedures. The causes of end-stage lung disease were primary pulmonary hypertension (n = 7), congenital heart disease (n = 5), cystic fibrosis (n = 4), pulmonary arteriovenous malformation (n = 2), graft- versus-host disease (n = 1), and desquamative interstitial pneumonitis (n = 1). Four (20%) patients had thoracic surgical procedures before the transplantation operation. The survival was 80% at a mean follow-up of 2 years. Immunosuppressive drugs included cyclosporine (n = 9) or FK 506 (n = 11) based therapy with azathioprine and steroids. Children were followed up by means of spirometry, transbronchial biopsy, and primed lymphocyte testing of bronchoalveolar lavage fluid. The mean number of treated episodes of rejection was 1.4 at 30 days, 0.5 at 30 to 90 days, and 1.4 at more than 90 days, and the first treated rejection episode occurred on average 28 days after the operation. Obliterative bronchiolitis developed in four (25%) of 16 patients surviving more than 100 days. Results of pulmonary function tests have remained good in almost all recipients. The greatest infectious risk was that of cytomegalovirus: one death and one case of pneumonia. Posttransplantation lymphoproliferative disease was diagnosed in two (12.5%) patients; both recovered. The most common complications were hypertension (25%) and postoperative bleeding (15%). Early results indicate that lung transplantation is a most promising therapy for children with severe vascular and parenchymal lung disease

Targeted Deletion of Kcne2 Causes Gastritis Cystica Profunda and Gastric Neoplasia

Gastric cancer is the second leading cause of cancer death worldwide. Predisposing factors include achlorhydria, Helicobacter pylori infection, oxyntic atrophy and TFF2-expressing metaplasia. In parietal cells, apical potassium channels comprising the KCNQ1 α subunit and the KCNE2 β subunit provide a K+ efflux current to facilitate gastric acid secretion by the apical H+K+ATPase. Accordingly, genetic deletion of murine Kcnq1 or Kcne2 impairs gastric acid secretion. Other evidence has suggested a role for KCNE2 in human gastric cancer cell proliferation, independent of its role in gastric acidification. Here, we demonstrate that 1-year-old Kcne2−/− mice in a pathogen-free environment all exhibit a severe gastric preneoplastic phenotype comprising gastritis cystica profunda, 6-fold increased stomach mass, increased Ki67 and nuclear Cyclin D1 expression, and TFF2- and cytokeratin 7-expressing metaplasia. Some Kcne2−/−mice also exhibited pyloric polypoid adenomas extending into the duodenum, and neoplastic invasion of thin walled vessels in the sub-mucosa. Finally, analysis of human gastric cancer tissue indicated reduced parietal cell KCNE2 expression. Together with previous findings, the results suggest KCNE2 disruption as a possible risk factor for gastric neoplasia

My own medicine: A doctor's life as a patient

Item consists of a digitized copy of an audio recording of a Vancouver Institute lecture given by Geoffrey Kurland on February 21, 2004. Original audio recording available in the University Archives (UBC AT 2720).Other UBCUnreviewedOthe

Comparative analysis of chest tube thoracostomy and video-assisted thoracoscopic surgery in empyema and parapneumonic effusion associated with pneumonia in children

Background: Controversy exists regarding the optimal management strategy for children having empyema or parapneumonic effusion as a complication of pneumonia. We hypothesized that video-assisted thoracoscopic surgery (VATS)-assisted drainage of pleural fluid and debridement of the pleural space is superior to a chest tube alone in the management of these patients. We further identified predictive factors - namely, presentation, radiographic findings, antibiotic usage, and pleural fluid features - that could predict the need for VATS rather than primary chest tube drainage. Methods: Forty-nine pediatric patients with pneumonia complicated by parapneumonic effusion or empyema treated at the Children\u27s Hospital of Pittsburgh (1997-2003) were divided into three groups according to the therapy instituted: Primary chest tube, chest tube followed by VATS, or primary VATS. The groups were analyzed in terms of demographics and outcome, as judged by pleural fluid analysis and hospital resource utilization. Demographic and outcome data were compared among groups using one-way analysis of variance and the Student t-test. Results: All groups were similar with respect to demographics and initial antibiotic usage. Patients undergoing primary VATS had a higher initial temperature, whereas radiographic findings of mediastinal shift and air bronchograms were more likely to be found in patients who underwent primary chest tube placement. Patients undergoing primary VATS demonstrated a significantly shorter total stay and lower hospital charges than the other groups. Forty percent of children started on chest tube therapy failed even with subsequent VATS, necessitating a significantly longer hospital course (18 ± 3 vs. 11 ± 0.8 days; p \u3c 0.05) and higher hospital charges ($50,000 ± 7,000 vs.$29,000 ± 1000) than those having primary VATS. Conclusions: Patients treated by primary VATS had a shorter stay and lower hospital charges than patients treated by chest tube and antibiotic therapy alone. There were no demographic, physiologic, laboratory, or chest radiographic data that predicted the selection of VATS as an initial treatment. These data suggest a strategy of primary VATS as first-line treatment in the management of empyema or parapneumonic effusion as a complication of pneumonia in pediatric patients. © 2008 Mary Ann Liebert, Inc

Feasibility of laparoscopic Nissen fundoplication after pediatric lung or heart-lung transplantation: Should this be the standard?

Background: Five-year graft survival in the pediatric lung transplant (LTxp) population is less than 50%, with obliterative bronchiolitis (OB) the leading cause of death at 1, 3, and 5 years post-transplant. Bronchiolitis obliterans syndrome (BOS), defined using spirometry values, is the clinical surrogate for the histological diagnosis of obliterative bronchiolitis. Surgical correction of documented gastroesophageal reflux disease (GERD) has been proposed as a means to potentially delay the onset of BOS and prolong allograft survival in adults before or after lung transplantation but only one such study exists in children. We have examined the safety and possible benefits of laparoscopic antireflux surgery in pediatric patients following lung (LTxp) and heart-lung transplantation (HLTxp). Methods: An Institutional Review Board (IRB)-approved retrospective chart review was performed to evaluate the outcomes and complications of laparoscopic antireflux surgery in pediatric lung and heart-lung transplant patients. Spirometry data were collected for BOS staging using BOS criteria for children. Results: Twenty-five lung and heart-lung transplants were performed between January 2003 and July 2009. Eleven transplant recipients, including six double-lung and five heart-lung (HLTxp), with a median age of 11.7 years (range 5.1-18.4 years), underwent a total of 12 laparoscopic Nissen fundoplications at a median of 427 days after transplant (range 51-2310 days). GERD was determined based upon clinical impression, pH probe study, gastric emptying study, and/or esophagram in all patients. Three patients already had a gastrostomy tube in place and two had one placed at the time of fundoplication. There were no conversions to open surgery, 30-day readmissions, or 30-day mortalities. Complications included one exploratory laparoscopy for free air 6 days after laparoscopic Nissen fundoplication for a gastric perforation that had spontaneously sealed. Another patient required a revision laparoscopic Nissen 822 days following the initial fundoplication for a paraesophageal hernia and recurrent GERD. The average length of hospital stay was 4.4 ± 1.7 days. Nine of the 12 fundoplications were performed in patients with baseline spirometry values prior to fundoplication and who could also complete spirometry reliably. One of these nine operations was associated with improvement in BOS stage 6 months after fundoplication; seven were associated with no change in BOS stage; and one was associated with a decline in BOS stage. Conclusion: It is feasible to perform laparoscopic Nissen fundoplication in pediatric lung and heart-lung transplant recipients without mortality or significant morbidity for the treatment of GERD. The real effect on pulmonary function cannot be assessed due to our small sample size and lack of reproducible spirometry in our younger patients. Additional studies are needed to elucidate the relationship between antireflux surgery and the potential for improving pulmonary allograft function and survival in children which has been previously observed in adult patients. © 2010 Springer Science+Business Media, LLC