The clinical value of lung imaging fluorescence endoscopy for detecting synchronous lung cancer.

Some patients with non-small cell lung cancer (NSCLC) will also have a synchronous malignant lesion. The lung imaging fluorescence endoscopy (LIFE) has proven better than conventional white light bronchoscopy (WLB) for visualizing premalignant lesions or early stages of lung cancer. In this study, the additional value of LIFE in diagnosing synchronous lung cancers as well as the impact of these findings on definite therapy was analyzed. Seventy-two patients with recently diagnosed NSCLC or pulmonary lesions highly suspect of lung cancer were studied. Patients underwent WLB, followed by LIFE. Apart from the primary lesions, additional abnormal and suspicious lesions seen at WLB and LIFE were scored separately and biopsied. Sixty-nine patients had NSCLC and three patients had small cell lung carcinoma. Apart from the primary lesion, one up to six additional endobronchial lesions were visualized in 48 patients by WLB and/or LIFE. High-grade dysplastic lesions were detected in ten patients, three of whom were eligible for surgery of the primary tumor after completion of the investigations. Three other patients (4.3%) had synchronous cancers (NSCLC). In one patient, the lesion was visualized by LIFE and by WLB. The other two malignant lesions were detected only by LIFE. In these three latter patients, diagnostic work-up and definite treatment was changed, as a result of detection of synchronous lesions. In conclusion, LIFE has additional value in detecting synchronous malignant lesions in patients with primary lung cancer. The detection of these lesions changed diagnostic work-up and definite treatment plan. Therefore, LIFE should be used in the work-up of patients with primary lung cancer.

Aromatase and COX-2 expression in human breast cancers.

We have investigated aromatase and the inducible cyclooxygenase COX-2 expression using immunocytochemistry in tumors of a series of patients with advanced breast cancer treated with aromatase inhibitors. Aromatase was expressed in 58/102 breast cancers. This is similar to the percentage previously reported for aromatase activity. Interestingly, aromatase was expressed in a variety of cell types, including tumor, stromal, adipose, and endothelial cells. Since prostaglandin E2 is known to regulate aromatase gene expression and is the product of COX-2, an enzyme frequently overexpressed in tumors, immunocytochemistry was performed on the tissue sections using a polyclonal antibody to COX-2. Aromatase was strongly correlated (P<0.001) with COX-2 expression. These results suggest that PGE2 produced by COX-2 in the tumor may be important in stimulating estrogen synthesis in the tumor and surrounding tissue. No correlation was observed between aromatase or COX-2 expression and the response of the patients to aromatase inhibitor treatment. However, only 13 patients responded. Nine of these patients were aromatase positive. Although similar to responses in other studies, this low response rate to second line treatment suggests that tumors of most patients were no longer sensitive to the effects of estrogen. Recent clinical studies suggest that greater responses occur when aromatase inhibitors are used as first line treatment. In the intratumoral aromatase mouse model, expression of aromatase in tumors is highly correlated with increased tumor growth. First line treatment with letrozole was effective in all animals treated and was more effective than tamoxifen in suppressing tumor growth. Letrozole was also effective in tumors failing to respond to tamoxifen, consistent with clinical findings. In addition, the duration of response was significantly longer with the aromatase inhibitor than with tamoxifen, suggesting that aromatase inhibitors may offer better control of tumor growth than this antiestrogen.

A patient with diabetes insipidus and periorbital swellings; Erdheim-Chester disease.

Erdheim-Chester disease is a rare multisystem disease in which a progressive xanthogranulomatous infiltration of several tissues can be seen. We describe a woman, known to have diabetes insipidus for ten years, with periorbital, retroperitoneal, mediastinal, axillar and inguinal involvement. On histological examination a granulomatous infiltration of fatty tissue and striated muscle was seen, consisting of Touton giant cells, histiocytes with foamy cytoplasm and lymphocytes. Immunohistochemical staining with CD-1a and S-100 was negative and on electron microscopy no Langerhans granules were seen. These findings led to the diagnosis of Erdheim-Chester disease. She had a good response on steroids. Because of some similar clinical features of Langerhans cell histiocytosis and Erdheim-Chester disease, a histiocyte disorder seems the most probable cause.

Combined surgical and medical approach to intravenous leiomyomatosis with cardiac extension.

Intravenous leiomyomatosis with cardiac extension is a rare entity. The case of a 49-year-old patient is described: she was operated on for intracaval intra-atrial leiomyomatosis. After an incomplete procedure (the tumour appeared not totally resectable), the patient was treated for a period of three years with a GnRH-analogue, whereafter the patient was doing clinically well and the tumour, although it regained some growth, was in a stable situation. This new strategy seems of certain importance to the surgeon, as it carries an alternative to a high-risk reoperation. To our knowledge, this is the first description of such a combined therapeutical approach.

Surgery for combined type small cell lung carcinoma.

BACKGROUND: Combined type small cell lung cancer (SCLC) has been reported to occur in, at most, 1% of all cases of SCLC. These tumours consist of SCLC with a component of squamous cell carcinoma and/or adenocarcinoma. The survival of patients with combined and pure SCLC after surgical resection was assessed. METHODS: From 1977 to 1994 2115 patients with bronchogenic carcinoma underwent pulmonary resection. From this group 26 patients (1.2%) were diagnosed as having combined SCLC and 74 patients (3.5%) as having pure SCLC. RESULTS: From the 26 patients with combined SCLC (mean age 66.4 years) three were classified as pT1N0M0, eight as pT2N0M0, four as postoperative stage II, and 11 as postoperative stage III. Histological examination showed a component of squamous cell carcinoma in 21 patients. There were 18 (69%) lobectomies, seven (27%) pneumonectomies, and one (4%) segmentectomy. In all patients surgery was thought to be curative. Overall hospital mortality was 4% (n = 1). Cumulative five year survival was 31% for all hospital survivors with combined SCLC postoperative stage I, 50% for those with pT1N0M0, and 25% for those with pT2N0M0 disease. No patients with postoperative stage II and III disease survived for five years. In the 74 patients with pure SCLC hospital mortality was 3% (n = 2); cumulative five year survival was 39% in patients with postoperative stage I disease, 46% for those with pT1N0M0 and 35% for those with pT2N0M0. When compared with pure SCLC, no significant differences in five year survival were evident in patients with postoperative stage I disease. CONCLUSIONS: Surgical resection in patients with combined SCLC postoperative stage I yields a cumulative five year survival of 31% while for those with stage II and III disease there were no survivors at five years. In patients with stage I combined or pure SCLC surgery can offer a long term disease free interval or may even be curative.

Aortitis, aortic valve incompetence, and left coronary ostium stenosis in a patient with C-ANCA-associated necrotizing vasculitis.

Aortitis with involvement of the aortic valve is rarely associated with vasculitis syndromes. We present a patient with antibodies to a neutrophil cytoplasmic antigen-associated (ANCA) vasculitis with renal failure who developed aortic incompetence as a result of aortitis which involved the aortic valve. Thickening of the aortic wall also caused stenosis of the left coronary ostium.

Ileal pouch arthritis: a case report.

A patient is described with arthritis of both wrists and tendinitis of one achilles tendon in the presence of severe pouchitis. The rapid disappearance of arthritis and tendinitis after removal of the pouch strongly suggests their relationship. The pathogenesis of arthritis in pouchitis has not been elucidated but may be the same as in ulcerative colitis. Rheumatologists should be aware of the occurrence of arthritis in patients with ulcerative colitis after the construction of an ileo-anal anastomosis with a so-called pouch.

An immunocytochemical analysis of rapidly progressive atherosclerosis in human vein grafts.

Aortocoronary vein grafts are known to develop atherosclerotic plaques usually superimposed on intimal hyperplasia. The cellular characteristics of these lesions have been studied with immune cytochemical techniques and compared with those in native coronary arteries. Fifteen stenosed grafts showed concentric intimal hyperplasia characterized by massive proliferation of smooth muscle cells (HHF-35+). The subendothelial layer contained numerous T lymphocytes (UCHL-1+, MT-1+) and to a lesser extent macrophages (HAM-56+). Eleven grafts had superimposed atherosclerotic plaques characterized by atheroma but otherwise showing the same cellular constituents. The atherosclerotic plaques in the venous grafts resembled those in the coronary arteries, the main difference being the occurrence of multiple atheromas (up to 4 in a single section), the high number of T lymphocytes and macrophages related to these sites and the presence of atheromas bordering directly onto the luminal surface. It thus appears that the development of atherosclerotic plaques in vein grafts is accompanied by a similar immune inflammatory reaction as in native coronary atherosclerosis, presumably in a more aggravated form. The latter phenomenon could relate to the more enhanced and rapidly progressive nature of vein graft atherosclerosis.

Pyruvate kinase activity and isozyme composition in normal fibrous tissue and fibroblastic proliferations.

Pyruvate kinase (PK) was studied in 57 fibroblastic and fibrohistiocytic proliferations and normal fibrous tissue (n = 10). The specific activity was significantly increased in malignant tumors (1.67 +/- 0.25) compared with normal tissue (0.26 +/- 0.04; P less than 0.001) and benign proliferations (0.52 +/- 0.05; P less than 0.005). Although an overlap exists between aggressive fibromatosis and the benign group, high values of PK activity are indicative of Grade 2 and 3 malignancy. Significant shifts in isozyme pattern, favoring the expression of K-type subunits were found in tumors with a metastasizing potential and aggressive fibromatosis. These changes in the isozyme pattern of PK in aggressive fibromatosis may act as another argument to place them in the category of malignant fibroblastic tumors.

Activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase in smooth muscle proliferation.

The specific activity of hexokinase, phosphofructokinase, aldolase, enolase, pyruvate kinase and glucose-6-phosphate dehydrogenase was measured in 41 smooth muscle cell tumors: 20 leiomyomas and 21 cases of leiomyosarcoma. Statistical analysis revealed no significant differences in specific activity between normal smooth muscle tissue and the benign and malignant tumors originating from it. Quantification of the isozyme composition of pyruvate kinase showed a significant shift in isozyme pattern towards K-type subunits in leiomyosarcomas as compared to leiomyomas.

Activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase in lipoblastic and neurogenic proliferations.

The alterations in specific activity and/or isozyme pattern of hexokinase, phosphofructokinase, aldolase, enolase, pyruvate kinase and glucose-6-phosphate dehydrogenase were studied in the tissue specimens of 26 patients with lipoblastic tumors and 28 patients with tumors of neurogenic origin. Although the biochemical data demonstrated that the activities of most enzymes studied were elevated in the specimens of the malignant tumors, only the differences in activity of hexokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase measured between benign and malignant neurogenic tumors were significant. In malignant tumors, especially those of neurogenic origin, the isozyme pattern of pyruvate kinase showed a shift towards K-type subunits.

Characterization of human soft tissue sarcomas in nude mice. Evidence for histogenic properties of malignant fibrous histiocytomas.

Twenty-two human sarcomas were grafted subcutaneously into nude mice. Twelve tumors grew successfully. Nine of these 12 tumors had an aneuploid DNA content, whereas only 1 of 10 nonsuccessful tumors was aneuploid. The 12 sarcomas included two leiomyosarcomas, two malignant schwannomas, one synovial sarcoma, and seven malignant fibrous histiocytomas (MFHs). With light and electron microscopic and immunolabeling studies the original and xenografted tumors (the latter for at least two generations) were histopathologically compared. The xenografted leiomyosarcomas showed ultrastructurally a more pronounced leiomyodifferentiation, and one of the malignant schwannomas a more pronounced schwannian differentiation. The second malignant schwannoma and the synovial sarcoma, however, remained unchanged. Five storiform pleomorphic MFHs expressed features that were not observed in the original tumors. Tumor cells of three of these xenografted sarcomas showed leiomyogenic differentiation (filamentous densities, pinocytotic vescicles, and desmin immunoreactivity), whereas cells of the two others demonstrated schwannian differentiation (long cytoplasmic processes, basal lamina). A xenografted myxoid MFH and a pleomorphic MFH gave rise to pleomorphic sarcomas composed of undifferentiated cells. It appeared that under transplantation conditions tumor cells of storiform pleomorphic MFH can differentiate into various directions.

Mesenchymoma of the lung (so called hamartoma): a review of 154 parenchymal and endobronchial cases.

In a series of 154 patients (116 male and 38 female) with so called pulmonary hamartoma the peak incidence was in the sixth decade, with only three patients less than 20 years of age. Sequential radiographs showed that in 55 patients the tumour first appeared in adult life and that in 53 it progressively increased in size. The age incidence and progressive growth leads to the conclusion that the tumour is a benign neoplasm rather than a hamartoma, consisting of various connective tissues intersected by clefts lined by respiratory epithelium. The epithelial elements are regarded as entrapped non-neoplastic inclusions and the tumour as a purely mesenchymal neoplasm: the name mesenchymoma therefore seems the most appropriate. There were two recurrences after simple enucleation, 10 and 12 years later. A total of 142 tumours were parenchymal, and only 12 were endobronchial. All lobes were affected but there was a slight preponderance in the left upper lobe. Four patients had two (synchronous) mesenchymomas. There was an associated bronchial carcinoma in 11 patients, synchronous in six and metachronous in five.

Malignant mixed mesodermal tumor of the ovary.

Mixed mesenchymal and epithelial tumors are highly malignant neoplasms most commonly found in the uterus. Rarely, histologically identical tumors occur in the ovary. We report a 70-yr-old woman with a malignant mixed Müllerian tumor of the ovary. The tumor contained heterologous foci of immature cartilage and striated muscle, in addition to carcinosarcomatous areas. Postoperative chemotherapy was administered, but she died within 5 mth with recurrent and metastatic tumor. A review of the literature concerning extrauterine malignant mixed Müllerian tumors is added.