Malignant pleural mesothelioma.
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Humans↗
Biomedical subjects
H I Pass
Publications and source records attributed to H I Pass.
Cytoreductive surgery prior to interleukin-2-based therapy in patients with metastatic renal cell carcinoma.
From May 1985 to December 1990, 93 patients with the clinical diagnosis of metastatic renal cell carcinoma and their primary tumor in place were evaluated for cytoreductive surgery as preparation for systemic therapy with regimens based on interleukin-2. These patients had typical sites of metastatic disease and manifestations of paraneoplastic syndromes. Patients underwent removal of the primary tumor, as well as debulking when this could be performed safely. Thirty-two percent of patients (30/93) had a second surgical resection in addition to their nephrectomy, frequently because of the large size of the primary tumor and its invasion of adjacent structures. Thirteen percent of patients (12/93) experienced postoperative complications. There were no perioperative mortalities. Forty percent of patients (37/93) who underwent nephrectomy could not be treated with immunotherapy, usually because of progression of disease. A preoperative ECOG status greater than or equal to 2 was the only significant risk factor associated with failure to undergo immunotherapy (P = 0.043). The response rate to immunotherapy in the 56 patients receiving interleukin-2 was 27 percent (4 CR, 11 PR).
Adolescent↗
Differential expression of platelet derived growth factor-beta in malignant mesothelioma: a clue to future therapies?
Malignant mesothelioma (MM) is resistant to most standard forms of treatment. Accordingly, novel therapies based on the genetic and autocrine growth characteristics are being investigated. Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells, is produced by several human malignant cell lines including MM and therefore may promote tumourigenesis by an autocrine mechanism. We investigated the expression of PDGF-beta mRNA in tumour specimens excised from 18 patients with MM. Total cellular RNA was successfully extracted from 16/18 frozen tumour specimens with guanidine isothiocyanate and purified by centrifugation through a caesium chloride gradient. Northern blots were prepared and probed sequentially with 32P-labelled PDGF-beta and beta-actin cDNA. Gene expression was quantitated by optical densitometry. Freshly elutriated human peripheral blood monocytes were stimulated to induce PDGF-mRNA expression with transforming growth factor-beta-1. This positive control was assigned an expression index (EI) of 1, with the EI for the tumour sample calculated as: PDGFpatient/Actinpatient/EI positive control. In the 16 tumour specimens with useable RNA, transcripts for PDGF-beta MRNA were detected. Northern blot analyses revealed elevation of PDGF-beta expression above control in 10/16 (63%) of MM patients. A 230% increase in PDGF-beta expression (EI = 1.62 vs. EI = 0.49) was found between the lowest and highest expression samples. The specimens from which the PDGF transcripts were derived were found histologically to contain 87% tumour and 13% contaminating normal cells, predominantly lymphocytes. The elucidation of the transcriptional regulation of growth factors which are implicated in the pathogenesis of MM may guide the development of more effective biologic therapies.
Blotting, Northern↗
Targetted phototherapy with sensitizer-monoclonal antibody conjugate and light.
Photodynamic therapy (PDT) was performed in vitro and in vivo using monoclonal antibody conjugated to hematoporphyrin (HP). The antibody (45-2D9) recognized a cell surface glycoprotein on cells derived from NIH 3T3 cells which were transformed with the ras oncogene (45-342). Radionuclide imaging with either In111 or I125 chelated to 45-2D9 or the isotype identical (IgG1) antibody MOPPC-21 revealed selectivity of 45-2D9 for 45-342 flank tumours in nude mice, and minimal targetting for a 45-342 clone which did not express the cell surface glycoprotein. The 45-2D9-HP conjugate resulted in selective killing of the 45-342 line compared with the parent line in vitro. At HP concentrations of 76 micrograms ml-1, the 45-2D9-HP conjugate resulted in significantly more long-term cures of PDT treated flank tumours compared with free HP at the same concentration. 45-2D9 alone had no effect on tumour growth. The antibody-HP conjugate resulted in significantly less local toxicity compared with standard Photofrin II PDT, and also achieved a greater number of long-term cures. This 'photoimmunotherapy' demonstrates the ability to treat established tumours with greater efficacy and decreased morbidity, probably due to specific sensitizer targetting which allows normal surrounding tissue to be spared upon illumination.
3T3 Cells↗
Intraoperative ultrasound in the evaluation of tumor involvement of the inferior vena cava.
The successful excision of genitourinary malignancies extending to the inferior vena cava relies heavily on accurate preoperative imaging. For the majority of these patients magnetic resonance imaging, inferior venacavography, abdominal ultrasound or abdominal computerized tomography will reliably predict the extent of inferior vena caval involvement by tumor. However, occasionally the results of these studies will conflict or be called into question intraoperatively. We report on 8 patients considered to be at risk for inferior vena caval involvement by tumor and for whom intraoperative ultrasound was obtained to clarify the presence or extent of thrombus. Five patients had renal cell carcinoma and 3 had adrenal carcinoma. In all patients concern as to the extent or presence of tumor was based on either inconclusive preoperative studies or unexpected intraoperative findings. In each case intraoperative ultrasound clearly visualized the inferior vena cava and established the presence or extent of tumor invasion. In 4 patients venacavotomy was avoided as a consequence of these findings. Intraoperative ultrasound is a useful tool that can accurately assess the inferior vena cava for possible tumor invasion, especially when the presence or extent of tumor involvement is not definitively established preoperatively.
Adolescent↗
Pulmonary cryptococcosis presenting as metastases in children with sarcomas.
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Adolescent↗
Pulmonary metastatic disease in ameloblastoma.
Ameloblastoma is a rare disease of odontogenic origin with indeterminate metastatic potential. The first site of metastatic disease is usually the lung. We report aggressive surgical treatment of a patient with bilateral disease with five subsequent recurrences. A review of the literature suggests that in the absence of effective chemotherapy or radiation, surgery should be considered the treatment of choice for metastatic ameloblastoma confined to the lung.
Adult↗
Photodynamic therapy for thoracic cancer: biology and applications.
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Humans↗
Effective reversibility of the signs and symptoms of hypercortisolism by bilateral adrenalectomy.
BACKGROUND: The long-term outcome of bilateral adrenalectomy in the management of patients with Cushing's syndrome has not been previously well studied. METHODS: We reviewed our long-term results in 34 patients treated with bilateral adrenalectomy between 1983 and the present. Fourteen presented with occult or metastatic ectopic adrenocorticotropic hormone (ACTH) syndrome, 10 with failed treatment of Cushing's disease, five with primary micronodular and four with massive macronodular adrenocortical disease and one with indeterminate cause of Cushing's syndrome. RESULTS: All patients underwent bilateral adrenalectomy. Of 19 patients who required antihypertensive medications before operation, 15 (79%) had significant improvement and were either off all antihypertensive medication or required less medication after operation. Of 7 patients who required medications for diabetes mellitus, after operation 6 (86%) required no medication or changed from injections to oral hypoglycemic agents. Of 9 patients with mood changes or depression, the symptoms of 8 (88%) resolved. Of 29 patients with documented weight gain, 23 (79%) showed marked weight loss. Of 13 hirsute patients, 10 (77%) had resolutions of symptoms. Of 21 patients with complaints of fatigue, the symptoms of 16 (76%) resolved. Of 8 women with amenorrhea, 6 (75%) had resolution of symptoms. Each patient in the primary adrenocortical disease group, except one with residual fatigue, had complete resolution of his or her symptoms. There was no difference in resolution of symptoms between the ectopic ACTH and Cushing's disease groups. Six patients died: in the ectopic ACTH group one died of suicide at 1 month, and four of metastatic tumor at 9, 24, 25, and 48 months, and the patient with macronodular adrenocortical hyperplasia died of a myocardial infarction at 30 months. The remainder of the patients have been followed for a mean of 32 months (3 to 67 months). None of the patients had any evidence of recurrent hypercortisolism. CONCLUSIONS: We conclude that bilateral adrenalectomy is a safe, effective, and long-lasting method to ameliorate the devastating signs and symptoms of hypercortisolism in patients with Cushing's syndrome.
ACTH Syndrome, Ectopic↗
Neoadjuvant chemotherapy for locally advanced gastric adenocarcinoma.
Gastric adenocarcinoma is typically diagnosed at an advanced stage, and even with "curative" gastrectomy, most patients die of recurrent disease. Neoadjuvant chemotherapy for locally advanced gastric cancer is an experimental treatment strategy that may increase resectability and improve survival for patients afflicted with an almost uniformly fatal neoplasm. At our institution, we are evaluating the efficacy of fluorouracil, leucovorin, and interferon alfa-2A administered for three cycles, followed by surgery and consolidation therapy for patients with T3-4, N1-2, M0 gastric adenocarcinoma. The rationale for the use of neoadjuvant therapy combined with radical extirpative surgery in this setting and related issues are discussed.
Adenocarcinoma↗
Surgical resection of metastatic renal cell carcinoma and melanoma after response to interleukin-2-based immunotherapy.
Thirty-one patients with disseminated melanoma or renal cell cancer (RCC) who had a limited relapse or persistent disease after a partial or complete response to interleukin-2 (IL-2)-based immunotherapy underwent resection of progressing tumors or residual sites of disease. There were no surgery-related deaths. The median time to disease progression after resection for patients with RCC (n = 16) and melanoma (n = 15) was 11 and 5 months, respectively. All patients with melanoma had tumor progression within 10 months of surgery. Seven of 16 patients with RCC were free of tumor progression 4 to 44 months after surgery. Three of 12 patients with RCC rendered disease-free by surgery remain disease-free after 2 years. These data suggest that surgical resection is a reasonable option in selected patients who have a relapse after responding to IL-2-based immunotherapy. Although this retrospective study could not determine the relative survival benefits of surgery and immunotherapy, it showed that resection of metastatic disease after a response to immunotherapy can result in significant disease-free survival in patients with RCC but not melanoma.
Carcinoma, Renal Cell↗
Randomized trial of neoadjuvant therapy for lung cancer: interim analysis.
The role of neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer remains undefined. Since 1987, 27 patients with non-small cell lung cancer, all with histologically confirmed metastases to the ipsilateral mediastinal lymph nodes, have been enrolled in an ongoing prospective, randomized trial at our institution. Thirteen patients have been randomized to preoperative etoposide-platinum (EP) chemotherapy-surgery-postoperative EP, and 14 other patients have been randomized to surgery-postoperative mediastinal irradiation (SRT). Both groups are similar in sex, age, weight loss, tumor location, preoperative pulmonary function, physiologic grade, and tumor histology. Eight of the 13 EP patients have responded as evidenced by a 50% or greater radiographic tumor shrinkage after two cycles. Complete tumor and nodal resection rates were similar: 11/13 EP patients versus 12/14 SRT patients. There was no operative mortality for the 27 patients. Median potential follow-up is 29.9 months for the EP group and 34.9 months for the SRT group. Preliminary results suggest a trend toward increased survival time for the EP group (median, 28.7 months) versus the SRT group (median, 15.6 months) (p2 = 0.095). Eleven of 12 resected SRT patients have had recurrence versus 8 of 11 resected EP patients. Time to recurrence reveals no significant differences between the two groups but a trend toward increased disease-free interval in the EP group (12.7 months versus 5.8 months, EP versus SRT). This interim analysis demonstrates the feasibility of such a trial; however, despite the trends, definitive conclusions await further accrual and study maturation.
Antineoplastic Combined Chemotherapy Protocols↗
Renal cell carcinoma: resection of solitary and multiple metastases.
Between 1985 and 1991, 23 patients underwent resection of pulmonary metastases from renal cell carcinoma, of whom 18 had previously received interleukin-2 based immunotherapies. Mean survival from exploration in all patients was 43 months. Survival after resection did not correlate with the number of nodules on preoperative tomograms, the number of nodules resected, or the disease-free interval. Patients who underwent complete resection of metastatic disease (n = 15), however, had a significantly longer survival (mean, 49 months; median not yet achieved) compared with patients with incomplete resection (median, 16 months) (p2 = 0.02). Two of the 15 patients who underwent curative resections are presently free of disease greater than 45 months after exploration. These data support surgical resection of isolated pulmonary metastatic disease from renal cell cancer.
Adult↗
Alterations in macrophage free radical and tumor necrosis factor production by a potassium channel activator.
The potassium channel activator nicorandil, under evaluation for antianginal management, has been shown to decrease neutrophil respiratory burst. Since our laboratory has demonstrated that reactive oxygen species (ROS) increase tumor necrosis factor (TNF) production, we hypothesized that nicorandil might decrease TNF production from a lipopolysaccharide (LPS) challenge via reduction of respiratory burst. Macrophage viability and TNF production were determined after an 18-hr exposure to 5.0 micrograms/ml LPS and varying concentrations of nicorandil. Nicorandil was not toxic to macrophages below 12 mM (94 +/- 3% viability versus control) and decreased ROS and TNF production. Intracellular superoxide production decreased from 164 +/- 24 OD550 to 99 +/- 6 OD550 with 10 mM nicorandil and extracellular superoxide decreased from 3108 +/- 111 to 1760 +/- 210 nM. Hydrogen peroxide production was also decreased by 10 mM nicorandil. TNF production in response to 5 micrograms/ml LPS decreased from 6.8 +/- 0.6 to 2.7 +/- 0.4 ng/ml with 10 mM nicorandil. Northern and slot blot analyses demonstrate that nicorandil acts at a post-transcriptional site. These data imply that nicorandil decreases macrophage TNF production from an LPS challenge, possibly through a reduction in respiratory burst. Such compounds may prove useful in the treatment of conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion injury, oxygen toxicity, adult respiratory distress syndrome, and septic shock.
Animals↗
Long term tolerance of thoracic organs to intraoperative radiotherapy.
The tolerance of mediastinal structures to intraoperative radiotherapy (IORT) was investigated in 3 separate animals trials using 49 adult foxhounds and one limited Phase I trial in 4 patients with Stage II or III non-small cell lung cancer (NSCLC). The 1- to 2-year results of these trials have been previously reported with significant toxicity found at dose levels over 20 Gy. We now report the results of five dogs reserved for long term studies and one Stage II NSCLC patient alive at 5 years. Two dogs received 20 Gy IORT and one received 30 Gy IORT to the esophagus, all three to a single 6 cm field with 9 MeV electrons. One control dog underwent surgery without irradiation. One dog received 20 Gy IORT to a single 5 cm mediastinal field with 13 MeV electrons following left pneumonectomy. At 5 years, all five dogs reserved for a long term evaluation were alive and evaluable with minimal endoscopic and radiographic abnormalities. The one patient alive at 5 years for evaluation received 25 Gy IORT to two matched 6 cm fields with 13 MeV electrons. She has stable dyspnea on exertion and there is no evidence of cancer by endoscopy. We conclude, based on these limited data, that IORT in the mediastinum may be safe at dose levels that do not exceed 20 Gy, and further careful evaluation at these lower treatment doses is warranted to determine efficacy.
Animals↗
Successful treatment of systemic Exophiala dermatitidis infection in a patient with chronic granulomatous disease.
Exophiala dermatitidis, one of the saprophytic dematiaceous fungi, is a rare cause of human infection that, when invasive, is nearly always fatal. Besides the more common subcutaneous infection usually caused by traumatic inoculation, infection can also spread hematogenously, in which case the organism has a distinct neurotropism. A patient with autosomal recessive chronic granulomatous disease of childhood who was found to have a progressive pulmonary and central nervous system infection with E. dermatitidis responded to an aggressive, multifaceted therapeutic approach. Scanning electron microscopy of the cultured conidiogenous cells confirmed that the manner of conidiogenesis is typical of the genus Exophiala. We report the first successful treatment of an infection involving the lungs and central nervous system by a combination of surgical resection of the pulmonary source and medical therapy with amphotericin B, flucytosine or ketoconazole, and transfused white cells, followed by a prolonged course of fluconazole.
Adult↗
Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism.
Persistent primary hyperparathyroidism due to mediastinal parathyroid adenoma was effectively treated by either angiographic ablation or median sternotomy in this study of 49 patients managed at the National Institutes of Health since 1977. Each patient presented here with symptomatic persistent primary hyperparathyroidism after failed initial surgical procedures done at other institutions. Each patient underwent extensive parathyroid localization procedures, including selective angiography, and most had a parathyroid adenoma localized to the mediastinum. Angiographic ablation, the deliberate injection of large doses of contrast material into the artery that selectively perfuses the adenoma, was initially successful in 22 of 30 procedures (73%) in 27 patients. Long-term control of persistent primary hyperparathyroidism was achieved in 17 of 27 patients (63%) by angiographic ablation. Each unsuccessful ablation could be easily salvaged by surgical resection. Surgical resection of the parathyroid adenoma by median sternotomy achieved immediate success in 24 of 24 procedures (p2 less than 0.02 versus ablation), and long-term cure in 23 of 23 evaluable patients (p2 less than 0.001 versus ablation). However, ablation did have benefits for the patients in whom it was successfully performed. It was associated with a significantly shorter hospital stay (median, 6 days versus 9 days for sternotomy, p2 less than 0.003), much less pain, and easier recuperation. Complications of each procedure were transient and similar in both groups. Operative resection is the most effective single means to eradicate mediastinal parathyroid adenoma; however, angiographic ablation can provide similar long-term control of hyperparathyroidism in 63% of patients with less pain and shorter convalescence than that seen in patients after median sternotomy. Our results suggest that angiographic ablation should be attempted as the initial procedure for patients with persistent primary hyperparathyroidism caused by an angiographically identified mediastinal parathyroid adenoma. Operation can be reserved for those who fail ablation.
Adenoma↗
Pulmonary metastases: MR imaging with surgical correlation--a prospective study.
The sensitivity of magnetic resonance (MR) imaging for detection of pulmonary metastases in 11 patients scheduled for thoracotomy and curative resection of metastases was evaluated with a prospective, controlled study. MR imaging performed at 0.5 T was compared with chest radiography, computed tomography (CT), and thoracotomy in 12 cases. (One patient had two separate occurrences of pulmonary metastases.) All images were interpreted in blinded fashion. When all MR sequences were interpreted together, MR imaging enabled correct identification of all patients with pulmonary nodules (100%). CT enabled detection of at least one nodule in all 12 cases (100%) by design; the sensitivity of chest radiography was only 64%. For individual nodules, MR imaging was at least as sensitive as CT (P2 less than .25 [two-sided value]) and significantly more sensitive than chest radiography (P2 less than .01). Among all MR sequences, short inversion time inversion-recovery sequences had the highest sensitivity for detection of individual nodules (82%).
Adult↗