Reoperative pulmonary metastasectomy for sarcomatous pediatric histologies.

BACKGROUND: The role for reoperative pulmonary metastasectomy in patients with "pediatric sarcomas" (osteosarcoma, nonrhabdomyosarcoma-soft tissue sarcoma, and Ewing's sarcoma) is undefined. METHODS: We reviewed our results for patients with these histologic presentations (median age, 17.5 years; range, 6 to 32 years) having two (70), three (27), or four (10) metastasectomies between January 1965 and March 1995 to define postresection survival and potential prognostic factors. Simple wedges (88 thoracotomies, 84%) were performed more frequently than anatomic (17 thoracotomies, 16%) resections. RESULTS: With a median potential follow-up of 12.7 years, median survival was 2.25, 3.60, and 0.96 years from the second, third, and fourth explorations, respectively. Primary tumor site, sex, histology, age, maximal metastasis size, and systemic chemotherapy did not influence survival. Resectability was the most important prognostic factor (5.6 versus 0.7 years, 5.2 versus 2.5 years, 2.2 versus 0.2 years, resectable versus unresectable, median survival from second, third, and fourth thoracotomy, respectively). Unresectability, disease-free interval less than 6 months between initial (ie, first) pulmonary resection and the second thoracotomy, and two or more preoperative nodules noted on the right were simultaneously negatively associated with survival from the second thoracotomy. Unresectability or finding two or more metastases negatively affected survival from the third thoracotomy. CONCLUSIONS: These data imply that repeat metastasectomy can salvage a subset of patients with sarcomatous pediatric histologic presentations who retain favorable prognostic determinants.

Pharmacokinetics of fentanyl during hyperthermic, isolated lung perfusion.

BACKGROUND: Hyperthermic, isolated pulmonary perfusion with tumor necrosis factor is a surgical procedure that isolates the pulmonary vasculature from the systemic circulation in patients with unresectable primary or metastatic disease confined to the chest. High drug levels are delivered to the perfused organ, avoiding systemic toxicity, and preventing loss of active drug through metabolism. METHODS: The pharmacokinetics of fentanyl are evaluated in three patients while the operative lung is hyperthermic, ventilated, and perfused with an asanguineous solution during nonpulsatile bypass. A loading dose of fentanyl, 1.5 microg/kg to 2.5 microg/kg, was given during the induction of anesthesia followed by a continuous infusion of 150 microg/hr. RESULTS: Results showed no difference in mean plasma fentanyl concentrations before, during, or after bypass and was consistent with clearance values previously reported in healthy adult surgical patients in the absence of an extracorporeal circuit. CONCLUSIONS: Adjustments in fentanyl dosing are not required before, during, or after hyperthermic, isolated pulmonary perfusion is established and a steady state of fentanyl is achieved.

Preoperative tumor volume is associated with outcome in malignant pleural mesothelioma.

OBJECTIVES: Our objective was to analyze the impact of preoperative and postresection solid tumor volumes on outcomes in 47 of 48 consecutive patients undergoing resection for malignant pleural mesothelioma who were treated prospectively and randomized to photodynamic therapy or no photodynamic therapy. METHODS: From July 1993 to June 1996, 48 patients with malignant pleural mesothelioma had cytoreductive debulking to 5 mm or less residual tumor by extrapleural pneumonectomy (n = 25) or pleurectomy/decortication (n = 23). Three-dimensional computed tomographic reconstructions of preresection and postresection solid tumor were prospectively performed and the disease was staged postoperatively according to the new International Mesothelioma Interest Group staging. RESULTS: Median survival for all patients is 14.4 months (extrapleural pneumonectomy, 11 months; pleurectomy/decortication, 22 months; p2 = 0.07). Median survival for preoperative volume less than 100 was 22 months versus 11 months if more than 100 cc, p2 = 0.03. Median survival for postoperative volume less than 9 cc was 25 months versus 9 months if more than 9 cc, p2 = 0.0002. Thirty-two of forty-seven (68%) had positive N1 or N2 nodes. Tumor volumes associated with negative nodes were significantly smaller (median 51 cc) than those with positive nodes (median 166 cc, p2 = 0.01). Progressively higher stage was associated with higher median preoperative volume: stage I, 4 cc; stage II, 94 cc; stage III, 143 cc; stage IV, 505 cc; p2 = 0.007 for stage I versus II versus III versus IV. Patients with preoperative tumor volumes greater than 52 cc had shorter progression-free intervals (8 months) than those 51 cc or less (11 months; p2 = 0.02). CONCLUSIONS: Preresection tumor volume is representative of T status in malignant pleural mesothelioma and can predict overall and progression-free survival, as well as postoperative stage. Large volumes are associated with nodal spread, and postresection residual tumor burden may predict outcome.

Bilateral lung collapse in an asthmatic patient during thoracotomy.

Bilateral sequential pulmonary atelectasis occurred during median sternotomy for metastasis resection in a 19-year-old women with asthma. Collapse was secondary to mucus plugging and resolved with mechanical ventilation, suctioning, and treatment for bronchospasm.

Surgically debulked malignant pleural mesothelioma: results and prognostic factors.

BACKGROUND: We analyzed morbidity and mortality, sites of recurrence, and possible prognostic factors in 95 (78 male, 17 female) patients with MPM on phase I-III trials since 1990. A debulking resection to a requisite, residual tumor thickness of < or = 5 mm was required for inclusion. METHODS: Preoperative tumor volumes were determined by three-dimensional reconstruction of chest computerized tomograms. Pleurectomy (n = 39) or extrapleural pneumonectomy (EPP; n = 39) was performed. Seventeen patients could not be debulked. Preoperative EPP platelet counts (404,000) and mean tumor volume (491 cm3) were greater than that seen for pleurectomy (344,000, 114 cm3). RESULTS: Median survival for all patients was 11.2 months, with that for pleurectomy 14.5 months, that for EPP 9.4 months, and that for unresectable patients 5.0 months. Arrhythmia (n = 14; 15%) was the most common complication, and there were two deaths related to surgery (2.0%). Tumor volume of > 100 ml, biphasic histology, male sex, and elevated platelet count were associated with decreased survival (p < 0.05). Both EPP and pleurectomy had equivalent recurrence rates (27 of 39 [69%] and 31 of 39 [79%], respectively); however, 17 of 27 EPP recurrences as opposed to 28 of 31 pleurectomy recurrences were locoregional (p2 = 0.013). CONCLUSIONS: Debulking resections for MPM can be performed with low operative mortality. Size and platelet count are important preoperative prognostic parameters for MPM. Patients with poor prognostic indicators should probably enter nonsurgical, innovative trials where toxicity or response to therapy can be evaluated.

Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma.

BACKGROUND: Patients with malignant pleural mesothelioma (MPM) usually die of progressive local disease. This report describes the results of a Phase III trial comparing maximum debulking surgery and postoperative cisplatin, interferon alpha-2b, and tamoxifen (CIT) immunochemotherapy with and without intraoperative photodynamic therapy (PDT) to determine (1) whether such a multimodal approach can be performed with minimum morbidity and mortality in malignant pleural mesothelioma (MPM), and (2) whether first-generation (i.e., 630-nm laser light, Photofrin II) intrapleural PDT impacts on local recurrence of survival. METHODS: From July 1993 to June 1996, 63 patients with localized MPM were randomized to either PDT or no PDT. The tumors of 15 patients could not be debulked to 5 mm. Patients assigned to PDT (n = 25) and no PDT (n = 23) were similar with respect to age, sex, tumor volume, and histology. RESULTS: The type of resection (11 pleurectomies and 14 pneumonectomies vs. 12 pleurectomies and 11 pneumonectomies), length postoperative stay, and ICU time were comparable (PDT vs. no PDT). There was one operative death (hemorrhage), and each group had two bronchopleural fistulas. Postoperative staging divided patients into the following categories: stage I: PDT, 2, no PDT, 2; stage II: PDT, 2, no PDT, 2; stage III, PDT, 21; no PDT, 17; stage IV, PDT, 0; no PDT, 2. Comparable numbers of CIT cycles were delivered. Median survival for the 15 non-debulked patients was 7.2 months, compared to 14 months for the 48 patients on protocol. There were no differences in median survival (14.4 vs. 14.1 months) or median progression-free time (8.5 vs. 7.7 months), and sites of first recurrence were similar. CONCLUSIONS: Aggressive multimodal therapy can be delivered for patients with higher stage MPM. First-generation PDT does not prolong survival or increase local control for MPM.

Somatostatin analogue in the localization and treatment of bronchial carcinoid tumours.

Octreotide scanning is increasingly being used to detect tumours with somatostatin receptors. Moreover, there is growing interest in the use of somatostatin analogues for the treatment of tumours with somatostatin receptors. This review documents the use at our institution of the octreotide scan in three patients with intrathoracic pathology, and comments on overall experience in the literature with this technology.

Isolated lung perfusion with tumor necrosis factor for pulmonary metastases.

BACKGROUND: A phase I trial was initiated to define the feasibility and safety of single-lung isolation perfusion with tumor necrosis factor-alpha, interferon-gamma, and moderate hyperthermia for patients with unresectable pulmonary metastases. METHODS: Twenty patients with lung metastases (Ewing's, 2; sarcoma, 8; melanoma, 6; other, 4) were considered for single-lung isolation perfusion with 0.3 to 6.0 mg of tumor necrosis factor-alpha and 0.2 mg interferon-gamma delivered through an oxygenated pump circuit. Sixteen perfusions were performed in 15 patients (bilateral in 1). Metastases were completely resected (no single-lung isolation perfusion) in 3 patients, 1 patient had extrapulmonary disease, and one single-lung isolation perfusion was aborted for mechanical reasons. RESULTS: There were no significant changes in systemic arterial blood pressure or cardiac output during perfusion. Systolic pulmonary artery pressure increased with isolation, but returned to pre-single-lung isolation perfusion levels after clamp release. The maximum systemic tumor necrosis factor-alpha level was 8 ng/mL, whereas pump-circuit levels ranged from 200 to 10,976 ng/mL. There were no deaths, and the mean hospitalization period was 9 days (range, 5 to 34 days). A short-term (6 to 9 month) unilateral decrease in perfused nodules was noted in 3 patients (melanoma in 1, adenoid cystic carcinoma in 1, renal cell carcinoma in 1). CONCLUSIONS: Future studies using a combination of biologic modifiers, chemotherapy, and hyperthermia should be pursued to define active cytotoxic agents that will preserve underlying pulmonary function.

Phase II trial of 5-fluorouracil, leucovorin, interferon-alpha-2a, and cisplatin as neoadjuvant chemotherapy for locally advanced esophageal carcinoma.

BACKGROUND: Most patients with esophageal carcinoma present with locally advanced disease and a poor prognosis. Surgery or radiation provides palliation for locally advanced esophageal carcinoma. The role of neoadjuvant therapy remains to be defined. We administered neoadjuvant chemotherapy consisting of 5-fluorouracil (5-FU), leucovorin, interferon-alpha, and cisplatin to 11 patients with locally advanced disease. METHODS: Eleven patients with squamous cell or adenocarcinoma of the esophagus were treated peroperatively with two to three cycles of combination chemotherapy. Nine patients underwent resection with curative intent. RESULTS: Six patients received three cycles of chemotherapy, and five received two. Dose reduction was necessary for two patients. One patient achieved a pathologic complete response, histologically confirmed. Of the eleven patients, two did not undergo surgery because of progressive disease during chemotherapy. Seven of the 9 patients relapsed after surgery and 2 have been disease free for 27 months. CONCLUSIONS: The combination 5-FU leucovorin, interferon-alpha-2a, and cisplatin administered in a neoadjuvant setting resulted in a median survival of 11.8 months with a median time to relapse of 7 months.

Role of tissue diagnosis in pulmonary involvement in pediatric human immunodeficiency virus infection.

BACKGROUND: Pulmonary complications occur commonly during HIV infection. The aim of this study was to evaluate the clinical value of lung tissue examination in the diagnosis and treatment of pulmonary disorders in children with HIV infection. METHODS: The medical records of 347 children enrolled between January, 1990, and April, 1994, into various antiretroviral therapy protocols were reviewed to identify patients who underwent a lung biopsy. RESULTS: Fourteen patients underwent diagnostic lung biopsies on 16 separate occasions. The most common radiologic findings were nodular infiltrates which were localized in 7 patients and diffuse in 6. Eight patients presented with fever and progressive respiratory distress unresponsive to empiric therapy, whereas the rest had progressive nodular infiltrates. The pathologic diagnoses included opportunistic infection in 7 patients, lymphocytic interstitial pneumonitis in 5, non-Hodgkin's lymphoma in 3 and interstitial fibrosis in 1. The biopsy led to a major change in the treatment of 7 patients which resulted in a significant improvement of the pulmonary process in all of them. In an additional patient the excisional biopsy proved curative. CONCLUSIONS: When patients are selected appropriately, lung biopsy might have a significant impact on therapy and outcome in HIV-infected children with pulmonary infiltrates.

Metastasectomy for sarcomatous pediatric histologies: results and prognostic factors.

We reviewed our experience of pediatric metastasectomy to define (1) morbidity/mortality in this population and (2) any preoperative or intraoperative prognostic predictors of survival. One hundred fifty-two patients with median age 19 years (range, 5 to 33 years) had 258 thoracic explorations (Ewing's sarcoma, 28; rhabdomyosarcoma, 6; nonrhabdomyosarcoma soft tissue sarcoma, 42; and osteosarcoma, 76). Resections were accomplished by 218 wedge resections, 19 anatomic resections, 14 wedge and anatomic resections, 4 wedge and chest wall resections, and 3 wedge resections/other procedures. An initial complete resection was accomplished in 121/152 patients (80%). With a median potential follow-up of 10.6 years, median survival from initial thoracotomy is 2.2 years. By the Cox proportional hazards model, three or more positive nodules (p = 0.021), histology other than osteosarcoma (p = 0.0054), and incomplete resection (p < 0.0001) were unfavorable prognostic factors for survival. Two or more positive nodules (p = 0.0049), left location (p = 0.0031), age 14 years or greater at diagnosis (p = 0.0052), or rhabdomyosarcoma (p = 0.0066) predicted shorter pulmonary progression-free survivals after resection. Nonrhabdomyosarcoma pediatric metastasectomy can yield selected long-term survival. Morbidity/mortality is low, and a complete resection, if possible, is paramount. Prognostic factors can be defined that can be used to define the limits of this therapy to the patient and family.

A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction.

BACKGROUND: The treatment of malignant pleural mesothelioma (MPM) continues to be inadequate with the use of standard techniques, including surgery, radiotherapy and chemotherapy. We initiated a phase II trial of immunochemotherapy with cisplatinum (25 mg/m2 four times weekly), interferon-alpha (5 mU/m2 s.c. three times weekly, and tamoxifen (20 mg orally twice a day for 35 days) (CIT) based on in vitro and in vivo data suggesting interrelating efficacy of this combination. METHODS: Since July 1991, 36 patients have been evaluable for response after receiving one to five cycles of CIT. Ten additional patients had debulking surgery followed by two cycles of postoperative adjuvant CIT commencing a mean of 6 weeks after surgery. RESULTS: Toxicity was acceptable (4% grade III/IV). One treatment-related death (2%) occurred, from myocardial infarction. A 19% partial response rate, objectively quantified using three-dimensional computerized tomographic (CT) measurement of solid disease volume, was recorded. The median survival for the seven responders was 14.7 months, whereas that of the nonresponders was 8 months (p2 = 0.2). Median survival for the entire group was 8.7 months. Preoperative size, platelet count > 360,000/ml, and nonepithelial histology were associated with shortened survival. CONCLUSIONS: The CIT regimen has some activity in MPM and can be delivered after debulking resection. In good-risk patients, as defined by favorable prognostic factors, a randomized trial using this combination may be warranted.

Pulmonary malignant lymphoma of mucosa-associated lymphoid tissue (MALT) arising in a pediatric HIV-positive patient.

A malignant lymphoma arising in the lung of a pediatric HIV-positive patient exhibited histologic and clinical features of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Clinically, the neoplasm consisted of a 4-cm mass in the left-upper lobe of the lung of a 7-year-old girl. The lung mass was surgically resected. Monoclonal immunoglobulin heavy and light chain gene rearrangements were shown by Southern blot. Monoclonality of light chain expression was demonstrated by immunohistochemistry. Coexpression of Leu-22 (CD43) by the tumor cells supported the diagnosis of lymphoma. The remainder of the pulmonary parenchyma distal to the mass was associated with pulmonary lymphoid hyperplasia/lymphocytic interstitial pneumonitis, which may have been a predisposing factor. Gastric MALT lymphomas have recently been described in adult HIV-antibody-positive patients. Ours represents the first reported case of a pulmonary MALT lymphoma in a pediatric HIV-positive patient. In addition, at age 7, this is the youngest patient reported with a MALT lymphoma.

Esophagopleural fistula: a complication of photodynamic therapy.

Mesothelioma of the pleura remains an incurable disease for which novel treatments are being investigated. One of these is intraoperative photodynamic therapy (PDT), using the principle of cell cytotoxicity produced by light-activated sensitization. We report a complication of this therapy that defined the maximal tolerated dose of PDT, ie, esophagopleural fistula, in two consecutive patients who had received the same dose of PDT at the time of extrapleural pneumonectomy.

The macrophage, TNF, and other cytokines.

A complex interplay of peptides known as the cytokines may have a tremendous influence over a number of inflammatory related conditions. Tumor necrosis factor occupies an early and central role in the initiation of cascades that ultimately influences a number of cell types involved in tissue inflammation, tissue rejection, cancer, and injuries from ischemia reperfusion. Only now are the cascades being defined and therapies being designed to interrupt the toxic effects of these cytokines and to treat malignancy.

Intrapericardial pheochromocytoma complicated by massive intraoperative hemorrhage.

Middle mediastinal pheochromocytomas are exceedingly rare. Because so few cases have been reported, consensus has not been reached regarding the anesthetic management of patients with these tumors. The use of cardiopulmonary bypass (CPB) for the resection of intrapericardial pheochromocytomas has met with varied success. We report the first documented case of successful anesthetic and surgical management of an acute, massive hemorrhage during the dissection of an intrapericardial pheochromocytoma, which was managed without cardiopulmonary bypass. Perioperative anesthetic considerations, including the risks and benefits of CPB, are discussed.

Thoracotomy for pulmonary mycoses in non-HIV-immunosuppressed patients.

Pulmonary mycoses can be life threatening in patients who are in an immunocompromised state stemming from defective host defenses or the use of certain treatment regimens. In 36 immunosuppressed patients undergoing thoracotomy for the treatment of pulmonary fungal disease, the underlying cause of immunosuppression was malignancy (n = 9), Wegener's granulomatosis (n = 4), hematologic disorders (aplastic anemia, 5-Q minus syndrome, or myelofibrosis) (n = 6), or chronic granulomatous disease of childhood (n = 17). The mean age of the patients was 25 years, and 89% were symptomatic (fever, n = 27; cough, n = 20; chest pain, n = 14; and other, n = 13). Chest x-ray studies revealed the presence of cavitary disease (n = 7), a mass (n = 8), infiltrates (n = 20), or cavity and infiltrate (n = 1). A preoperative diagnosis was lacking in 23 of the 36 patients. Procedures included wedge biopsy (n = 13), segmentectomy with or without wedge or chest wall resection (n = 5), lobectomy with or without chest wall resection (n = 16), wedge resection plus completion pneumonectomy (n = 1), and segmentectomy plus completion pneumonectomy (n = 1). Fungi identified included Aspergillus (n = 23), Zygomycetes (n = 4), Cryptococcus (n = 3), and other (n = 6; 1 each), and specific antifungal treatment was instituted in 34 of the patients (94%). The 31% operative (ie, < 30-day or inhospital) mortality was chiefly due to multiorgan system failure (9/11).(ABSTRACT TRUNCATED AT 250 WORDS)

Desmopressin acetate in cardiac surgery: a double-blind, randomized study.

Use of desmopressin acetate (DDAVP) for patients having cardiac surgery is controversial. We did a double-blind, randomized study of 83 patients having cardiac operations at Georgetown University Hospital. The effect of DDAVP on bleeding as compared to placebo was evaluated by blood loss, replacement volume, and laboratory tests. There were no significant differences in baseline and intraoperative data between the DDAVP (n = 40) and placebo (n = 43) groups. Total drainage for the first 24 postoperative hours was 1,214 mL (+/- 78) for the DDAVP group and 1,386 mL (+/- 116) for the placebo group (not significant). There were no significant differences in replacement therapy. In this study, administration of DDAVP did not decrease bleeding.

A method to facilitate subxiphoid pericardiotomy.

Pericardial effusion can be treated effectively by the technique of subxiphoid pericardial window. We present a case in which the Cooper retractor designed for transcervical thymectomy facilitated this operation. When available, the Cooper retractor can be useful in selected patients.