Search

Byline: Lary A. Robinson, Elizabeth C. Reed, Timothy A. Galbraith, Anselmo Alonso, Anthony L. Moulton, William H. Fleming Abstract: Standard antifungal medical therapy of invasive pulmonary aspergillosis that occurs in immunocompromised patients with hematologic diseases with neutropenia or in liver transplant recipients results in less than a 5% survival. In view of these dismal mortality rates, we adopted an aggressive approach with resection of the involved area of lung along with systemic antifungal therapy when localized invasive pulmonary aspergillosis developed in these patients. Between January 1987 and December 1993, 14 patients with hematologic diseases and 2 liver transplant recipients underwent resection of acute localized pulmonary masses suggestive of invasive pulmonary aspergillosis a median of 7.5 days (range 1 to 45 days) after the diagnosis was clinically suggested and confirmed by chest computed tomographic scans. Operative procedures done included two pneumonectomies, one bilobectomy with limited thoracoplasty, nine lobectomies, and five wedge resections (one patient with hematologic disease had two procedures). All patients were treated before and after the operation with antifungal agents. Nine (64%) of 14 patients with hematologic disease and 2 (100%) of 2 liver transplant recipients survived the hospitalization with no evidence of recurrent Aspergillus infection after a median 8 months of follow-up (range 3 to 82 months). The five hospital deaths (all patients with hematologic diseases) occurred a median of 20 days after operation from diffuse alveolar hemorrhage in three, graft-versus-host disease in one, and multiple organ system failure with presumed disseminated Aspergillus infection in one. Four of the five deaths were in patients with allogeneic bone marrow transplants. Two of the three patients requiring resection of multiple foci of infection died, as did the only patient who was preoperatively ventilator dependent. In immunocompromised patients with hematologic diseases or liver transplantation with invasive pulmonary aspergillosis, early pulmonary resection should be strongly considered when the characteristic clinical and radiographic pictures appear. (J T HORAC C ARDIOVASC S URG 1995;109:1182-97) Author Affiliation: Omaha, Neb Article Note: (footnote) [star] From the Section of Cardiothoracic Surgerya and Section of Oncology and Hematology,b University of Nebraska Medical Center, Omaha, Neb., [star][star] Read at the Seventy-fourth Annual Meeting of The American Association for Thoracic Surgery, New York, N.Y., April 24-27, 1994., a Address for reprints: Lary A. Robinson, MD, Division of Cardiothoracic Surgery, University of South Florida, 12902 Magnolia Dr., Tampa, FL 33612-9497., aa *Present address: Division of Cardiothoracic Surgery, The Miriam Hospital, Brown University, 164 Summit Ave., Providence, RI 02906., acents 0022-5223/95 $3.00 + 0, acentsacents 12/6/62948

BACKGROUND: Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow transplantation and is associated with very high mortality. This disorder's association with pulmonary inflammation, its coincidence with marrow recovery, and the usefulness of corticosteroids for treating other pulmonary hemorrhage syndromes provided the rationale for this study. METHODS: We retrospectively studied 65 episodes of diffuse alveolar hemorrhage that had occurred in 63 of 603 consecutively treated patients who had undergone high-dose chemotherapy with bone marrow transplantation. Patients were divided into three groups according to the therapy they had received for diffuse alveolar hemorrhage: supportive therapy alone (n = 12); low-dose corticosteroids (30 mg or less of methylprednisolone or its equivalent; n = 10); and high-dose corticosteroids (more than 30 mg methylprednisolone or its equivalent; n = 43). The primary outcome measures were overall survival and survival to hospital discharge, occurrence of respiratory failure requiring intubation, and development of infections subsequent to the diagnosis of diffuse alveolar hemorrhage. RESULTS: Overall survival at the end of the follow-up period was significantly higher for the highdose corticosteroid group compared with the supportive therapy group (P = 0.005); however, treatment with low-dose steroids did not increase survival over supportive therapy alone (P = 0. 198). In addition, survival to discharge was significantly increased for the high-dose group compared with the other two groups combined (33% versus 9. 1 %, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of the 22 unintubated patients in the high-dose group compared with 9 of the 10 initially unintubated patients in the other two groups (P = 0.056). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticosteroid treatment significantly increased the risk of infections (P >0.4, all comparisons). CONCLUSIONS: in this study, high-dose corticosteroid therapy for diffuse alveolar hemorrhage related to bone marrow transplantation was associated with improved total survival and survival to hospital discharge, and decreased development of respiratory failure in these patients. These results suggest the therapy is beneficial, and further prospective studies are warranted to verify the effectiveness of the treatment.

PURPOSE: A prospective study to determine the usefulness of quantitative bacterial cultures of fluid obtained via fiberoptic bronchoscopy and bronchoalveolar lavage as an aid in the diagnosis of bacterial pneumonia. PATIENTS: AND METHODS: All patients undergoing fiberoptic bronchoscopy with bronchoalveolar lavage during a 6 1/2-month period. Presence of pneumonia was determined using clinical, radiographic, laboratory, and histologic data. Quantitative bacterial cultures of bronchoalveolar lavage fluid were determined using a 1-[mu]L culture loop. RESULT: Quantitative bacterial cultures of bronchoalveolar lavage (BAL) fluid were sensitive and specific predictors of bacterial pneumonia. Using [10.sup.3] colony-forming units (cfu)/mL as the threshold value for a positive culture, we determined the sensitivity and specificity to be 90% and 97%, respectively. The data were also analyzed for the subgroups of patients who were intubated or were receiving antibiotics. The sensitivity and specificity were 78% and 96% for the group of patients receiving antibiotics and 100% and 82% for the group of patients intubated for more than 24 hours at the time of BAL. Values for the area under the receiver operating characteristic curve for the 3 groups were 0.94,0.88, and 0.96, respectively. CONCLUSIONS: Quantitative bacterial cultures of BAL fluid are sensitive and specific in the diagnosis of bacterial pneumonia. The use of antibiotics at the time of BAL reduces the sensitivity of the test, and prolonged intubation reduces the specificity of the test.

Hodgkin's disease is often curable with radiotherapy and chemotherapy, and cure may even be possible after the failure of an initial chemotherapy regimen. However, a poor prognosis awaits patients with early relapse after complete remission; those who do not achieve remission with chemotherapy; and those who do not achieve remission even after more than one chemotherapy regimen. Autologous bone marrow transplantation (ABMT), a procedure in which previously removed and stored bone marrow is reinfused into a patient after extremely high doses of chemotherapy are given, is successful for treating many malignancies, but is often withheld until late in the course of Hodgkin's disease. To determine the optimal time for ABMT in relapsed Hodgkin's disease, 70 patients were studied who underwent this procedure after chemotherapy treatment with high-dose cyclophosphamide, carmustine, and etoposide. All patients had been treated with at least one previous chemotherapy regimen, and 29 had been treated with 3 or more. Forty percent of the patients had received radiotherapy as part of their initial treatment. Results showed that 59 percent of the patients who underwent ABMT achieved a complete remission; 11 percent responded partially; 19 percent did not respond; and 11 percent died. The 4-year disease-free survival was approximately 27 percent, and 4-year survival was approximately 47 percent. Patients treated earlier in the course of the disease fared significantly better than those in whom several chemotherapy regimens failed. High-dose chemotherapy plus ABMT appears more effective than salvage chemotherapy (another regimen begun after failure) for patients with relapsed Hodgkin's disease. This treatment should be carried out as soon as possible after relapse. (Consumer Summary produced by Reliance Medical Information, Inc.)

Liver transplants are associated with a high incidence of fungal infections - as high as 28 percent. Prolonged use of antibiotics, indwelling catheters and immunosuppressive therapy may predispose the transplant recipient to these fungal infections. A retrospective study was undertaken of 307 liver transplant patients to determine the incidence and severity of these fungal infections, identify risk factors, and evaluate outcome and treatments. There were 91 infections identified in 72 liver transplants (23.8 percent). Candida, an organism normally found in the gastrointestinal tract and other areas of the body, was responsible for 83.5 percent of the infections. The infections included generalized infection (19 cases), inflammation of the abdominal cavity (17), and inflammation of the lungs (15). The infection was identified within the first two months in 84.7 percent of cases; the average was 16 days after transplant. Early identification is a problem; the main clinical problem was widespread infection. Risk factors identified included: retransplantation, reintubation, need for blood transfusion during surgery, urgent need for the operation, as well as number of steroid doses given, bacterial infection with antibiotic treatment, and vascular complications. Fungal infection was associated with decreased survival; 50 percent, versus 16.5 percent of patients without fungal infection. Treatment with amphotericin B was successful in 63 cases (74.1 percent). These findings indicate that fungal infection is a major cause of morbidity and mortality in liver transplant patients; this is related to specific risk factors, suggesting the need for effective preventive measures. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cytomegalovirus (CMV) has become the most important infectious agent in patients who undergo organ transplantation, due, in large measure, to the immunocompromised condition of the host. Infection with CMV may be the result of exposure to infected blood products or the transplanted organ, of reactivation of latent virus, or of reinfection. Liver transplant patients often develop infections, which are a serious cause of illness and death. To learn more about CMV disease among liver transplant recipients, the records of 211 patients (127 adults, 84 children) at one medical facility were reviewed. Patients were followed-up for an average of 13 months. Thirty-seven retransplantation procedures were performed for the whole group. When CMV disease was diagnosed, antiviral therapy with intravenous ganciclovir was initiated and patients' clinical, viral, and tissue biopsy results noted. Results showed that 73 patients (34.6 percent) experienced at least one episode of CMV disease, with a slightly higher incidence among adults. The diseases that necessitated liver transplantation are enumerated; in adults, there was no diagnosis consistently associated with subsequent CMV disease. In children, however, postnecrotic cirrhosis (a degenerative condition associated with tissue death) tended to be followed by CMV disease more than other disorders, with a lower CMV disease frequency among children with metabolic disorders. The risk of CMV disease was highest in patients who received livers from donors whose blood tested positive for CMV, from those who underwent treatment with agents to suppress lymphocyte proliferation for immunosuppression, and from those who underwent retransplantation. Primary disease (11 people) usually developed in the transplanted liver and had a high recurrence rate; however, it responded to ganciclovir in all cases. Control of CMV disease by this drug was achieved in approximately 94 percent of all cases. A discussion is provided of CMV disease in transplant recipients, and the lack of information regarding the effects of ganciclovir on liver transplant recipients is noted. Prompt diagnosis and preventive therapy are the key elements of treating this disorder in such patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

With current immunosuppressive regimens, viral disease has become an important source of morbidity after orthotopic liver transplantation. Over a 5‐year period, we retrospectively analyzed 422 liver transplants in 370 recipients (242 adults, 128 children) under cyclosporine and prednisone immunosuppression. A total of 108 patients (29.2%) received intravenous ganciclovir for viral disease, including 103 for cytomegalovirus (CMV) disease and 5 for Epstein‐Barr virus (EBV) disease. A total of 132 episodes of CMV disease (103 initial, 29 relapse) were treated with ganciclovir, including 22 patients with primary CMV disease. Opportunistic viral hepatitis was the most common clinical presentation of viral disease while recurrent disease often involved extra‐hepatic sites (especially pulmonary). The majority of cases of viral disease (both initial and relapse) were confined to single organ involvement (81.0%), at which time ganciclovir therapy was begun at a dose of 5 mg/kg twice daily for 2 weeks (with dosage adjustments for renal dysfunction). The initial diagnosis of CMV disease was made at a mean time after transplantation of 38 days, with a mean duration of ganciclovir therapy of 16 d. A prompt and lasting response, characterized by clinical improvement and negative viral cultures, was documented in 74 cases (71.8%). Fourteen additional patients were successfully retreated with ganciclovir for CMV relapse, so that CMV disease was ultimately controlled in 85.4% of cases. EBV disease was diagnosed at a mean time of 124 d after transplantation, with a mean duration of ganciclovir therapy of 39 d. Four cases (80%) were successfully treated. Overall patient survival after ganciclovir therapy is 79.0% with a mean follow‐up of 24 months. Adverse drug effects included significant leukopenia and thrombocytopenia in 7 patients (6.5%), with 2 requiring drug withdrawal. Conclusion: ganciclovir is a safe and effective agent for the treatment of viral disease in liver transplantat recipients. The availability of ganciclovir has resulted in successful treatment of viral disease without dramatic reductions in immunosuppression, thus permitting successful rescue of the patient and allograft with an acceptably low incidence of toxicity and viral relapse.