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Biomedical subjects

E Wilander

Publications and source records attributed to E Wilander.

At least 145 records · Page 8Linked to original sources

Interferon-mediated in vivo induction of beta 2-microglobulin on small-cell lung cancers and mid-gut carcinoids.

Selected neuroendocrine tumors, such as small cell lung cancer (SCLC), and neuroblastoma express markedly diminished class I major histocompatibility complex (MHC) antigens (HLA framework and beta 2-microglobulin, beta 2m). Another neuroendocrine tumor, mid-gut carcinoid, also expresses reduced beta 2m antigen as demonstrated herein. Antigen expression is greatly enhanced on SCLC cell lines by in vitro exposure to interferon (IFN). To determine whether IFN mediates similar effects in vivo, we examined by immunoperoxidase staining beta 2m expression in paraffin-embedded tumor tissue sections obtained from 4 SCLC and 7 mid-gut carcinoid patients before and after receiving partially purified human leukocyte IFN-alpha therapy. Before IFN treatment, 3/4 SCLC tumors and 5/7 mid-gut carcinoids did not express beta 2m. By contrast, all tumors showed considerable expression of beta 2m after IFN therapy. Induction of class I antigens on tumor cells deficient in such expression may be one mechanism by which IFN exerts antitumor effects. We believe this is the first report of in vivo induction of class I MHC antigens in epithelial tumor cells in humans.

Carcinoid Tumor↗

Primary bronchial and ovarian carcinoid tumors in the same patient: a case report and histopathologic analysis.

The first case report of a 58-year-old woman with two different primary carcinoid tumors is presented. The bronchial carcinoid exhibited a mosaic pattern, whereas the ovarian tumor showed both insular and trabecular patterns. No teratomatous component was observed in the ovary. Both tumors presented an argyrophil reaction and neuron-specific enolase (NSE) immunoreactivity. The ovarian carcinoid contained a cell population of argentaffin and serotonin immunoreactive cells, while the bronchial carcinoid was unreactive. Peptide hormone immunostaining disclosed the presence of glucagon and pancreatic polypeptide (PP) in the bronchial carcinoid, whereas the ovarian carcinoid showed no immunoreactivity with the antisera used. The patient was treated surgically (bilobectomy of the right lung, 1978, and total abdominal hysterectomy and bilateral salpingo-oophorectomy, 1984) and is now well with normal blood chemistry, normal urinary HIAA, and normal routine X rays of the lungs and the gastrointestinal tract, as well as normal ultrasonography of the abdomen and the liver.

Bronchial Neoplasms↗

Nonantral gastric carcinoid tumours associated with hypergastrinaemia.

Nonantral gastric carcinoid tumours in association with pronounced hypergastrinaemia are reported in 6 patients. It is suggested that the hypergastrinaemia, as a result of lack of a negative acid feedback inhibition in an achlorhydric stomach, promoted the tumour development, possibly initiated by action of carcinogenic nitrosamines, in the gastric juice.

Adult↗

Treatment of malignant carcinoid tumors with human leukocyte interferon: long-term results.

Thirty-six patients with malignant carcinoid tumors were treated with human leukocyte interferon (IFN) im at doses of 3-6 megaunits/day. The origins of the primary tumors were as follows: mid-gut (29 patients); pulmonary (four); rectal (one); ovarian (one); and unknown (one). Nineteen of the 36 patients had previously been treated with cytotoxic agents, streptozocin plus 5-fluorouracil or doxorubicin, but showed progressive disease. With IFN objective tumor responses were seen in 17 of the 36 patients (47%): in 14 of the 29 patients with mid-gut carcinoids (48%) and in three of the four patients with lung carcinoids (75%). The median duration of response was 34 months. Stable disease was noted in 14 of 36 patients (39%), all presenting mid-gut carcinoids. The median duration of stable disease was 25 months. Progressive disease from the start of IFN therapy was seen in five patients (14%). All responders except one had a greater than 50% reduction of urinary 5-hydroxyindoleacetic acid or alpha-human chorionic gonadotropin, whereas four patients also had a significant reduction of tumor size on computerized tomographic scan or at laparotomy. Two patients achieved complete remission. Improvement of clinical manifestations of the carcinoid syndrome was seen in all patients with objective response. Adverse effects including influenza-like syndrome, reduction of blood cells, chemical signs of liver dysfunction, and disturbed lipid metabolism occurred but were reversible or could be circumvented by dose reduction. Autoimmune phenomena were also noted such as development of thyroid autoantibodies with thyroiditis, SLE syndrome with antinuclear factors, and parietal cell antibodies with pernicious anemia. IFN therapy seems to be very effective in controlling tumor-secreted substances and thus giving relief of clinical symptoms. It also arrests tumor growth for extended time periods (median, 2 years). The adverse effects are surmountable and less severe than with cytotoxic therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Interferon-induced nuclear DNA alterations in malignant carcinoid tumors in vivo.

Tumor cell specimens were obtained by ultrasonically guided percutaneous needle liver biopsy from 23 patients with metastatic small intestinal carcinoid tumors. The patients were admitted to the hospital for antitumor therapy (streptozocin, 5-fluorouracil, and leukocyte interferon). The tumor cell samples were used for DNA cytofluorometry. All tumors (12 cases) from untreated patients exhibited diploid DNA stem lines with low proliferative activity. The mean number of tetraploid cells was 8%. Altered nuclear DNA records were obtained in tumors of 8 patients, all of which were treated with leukocyte interferon at 3-6 X 10(6) IU/day for 4-32 months. The DNA records in these tumors varied, but they were mainly in the range between diploid and tetraploid values. In some cases several nuclear DNA peaks were observed within the limits for the cell cycle. It is assumed that the interferon treatment was responsible for the development of altered DNA cell lines because: 1) all untreated tumors yielded regular diploid DNA histograms, 2) interferon was the only drug administered to all patients with tumors displaying altered DNA records, and 3) modal diploid DNA values were observed prior to the interferon treatment in some patients. It is suggested that interferon in vivo blocked carcinoid tumor cell populations in different phases of the cell cycle. This result might explain the nuclear DNA profiles registered in the treated patients as well as the therapeutic effect obtained by interferon.

Adult↗

Bronchial carcinoids and phaeochromocytomas. A comparative study with special emphasis on S-100 protein, serotonin and neuron-specific enolase (NSE) immunoreactivity.

A comparative study of bronchial carcinoids (9 cases) and phaeochromocytomas (8 cases) were performed. Both types of tumour exhibited neuron-specific enolase (NSE) immunoreactivity and an argyrophil reaction, and displayed a few scattered argentaffin and serotonin immunoreactive tumour cells. In addition, four of the nine bronchial carcinoids and six of the eight phaeochromocytomas were S-100 protein immunoreactive. The stained cells were located mainly in the periphery of the tumour cell aggregates and possessed long cytoplasmic processes surrounding unreactive tumour cells. The similarity between the two tumour types, especially in their morphology and S-100 protein immunoreactivity, indicates that bronchial carcinoids, or at least some of them, are histogenetically closely related to phaeochromocytomas and might derive from the peripheral nervous system.

Bronchial Neoplasms↗

Adrenal gland surgery. Preoperative location of lesions, histologic findings and outcome of surgery.

The accuracy of various techniques for preoperative location of adrenal lesions was studied in 55 consecutive cases, and the perioperative course and outcome of surgery were analyzed. CT correctly located 94% of all adrenal tumours, was less accurate (42%) in hyperplasia and gave no false-positive results. Selective angiography revealed 75% of the tumours, but was likewise diagnostically inadequate in adrenal hyperplasia. Adrenal venous sampling correctly located 80% of tumours and of hyperplasia. In hyperplasia it was the single most successful procedure for detecting the site of adrenal hyperfunction. Phlebography gave misleading information in almost 45% of cases. The perioperative complications included splenic rupture necessitating splenectomy (3 cases), superficial wound infection (2), pneumonia (4) and subphrenic abscess (1). There were no perioperative deaths. The study indicated CT to be the principal procedure for preoperative location of adrenal disorders. In some cases with adrenal hyperfunction, venous sampling should be added. Adrenal surgery can be performed with low morbidity and no mortality and with favourable long-term outlook in cases of benign lesion.

Adolescent↗

Nuclear DNA in intestinal carcinoid tumors. A study before and after cytotoxin (streptozotocin and 5-fluorouracil) treatment.

Imprint cytology specimens of metastases of intestinal carcinoids obtained by percutaneous biopsy were analysed cytofluorometrically with regard to nuclear DNA records. All untreated tumors (nine cases) exhibited diploid DNA values with a relatively low proliferative activity (less than 2% nuclei in S-phase region). The mean number of tetraploid cells was 5%. Cytofluorometry also was performed on five tumor metastases treated with the cytotoxin streptozotocin and 5-fluorouracil. After treatment, an increase in the number of tetraploid cells (mean value, 30%) was noted, indicating that the cytotoxin treatment (possibly streptozotocin) on the tumor cells in vivo blocked progression from G2 to M phase. The current cytofluorometric analyses show that diploid nuclear DNA records and a low proliferative activity is a characteristic of malignant carcinoid tumors of the intestine. Due to regular DNA histograms in the carcinoid tumors, it is suggested that reliable studies are permitted of the effect of cytotoxins on the different phases of the cell cycle in vivo.

Aged↗

Serotonin in fore-gut carcinoids. A survey of 60 cases with regard to silver stains, formalin-induced fluorescence and serotonin immunocytochemistry.

A series of 60 fore-gut carcinoid tumours was examined with regard to serotonin content after application of three different techniques, namely: the argentaffin reaction, formalin-induced fluorescence according to Falck-Hillarp and immunocytochemistry with monoclonal antibodies to serotonin. To evaluate the staining-fluorescence of individual tumour cells, the methods were applied to identical tumour sections. Twelve tumours demonstrated serotonin-immunoreactive cells, six of which were also argentaffin. Four tumours contained argentaffin cells but no serotonin-immunoreactivity. With the use of all three techniques, three types of tumour cells occurred, namely: serotonin-immunoreactive, non-argentaffin and non-fluorescence cells, serotonin-immunoreactive, argentaffin and fluorescent cells, and non-serotonin immunoreactive, argentaffin and non-fluorescent cells. The first (serotonin-immunoreactive) cell type was most frequently found in the tumours. One gastric carcinoid in which the argentaffin cells exceeded the serotonin-immunoreactive cells, a positive reaction was found with the modified Warthin-Starry reaction for demonstrating melanin. Since none of the techniques used for visualization of serotonin in endocrine tumours is unquestionably specific and since they do not give identical results, it is indicated that for a more accurate identification of serotonin in fore-gut carcinoid tumours, a positive reaction with at least two of the applied techniques is desirable.

Bronchial Neoplasms↗

S-100 protein in carcinoid tumours of appendix.

A series of 12 carcinoid tumours of the appendix were examined with regard to S-100 protein immunoreactivity. All tumours were both argentaffin and argyrophil, and displayed immunoreactivity after application of a monoclonal antibody against serotonin. The S-100 protein immunoreactivity appeared in 11 of the 12 tumours, preferably in cells presumably of Schwann cell origin with long slender processes localized at the periphery of the carcinoid tumour buds. Immunoreactive cells with cytoplasmic processes were also seen extending between individual tumour cell in the tumour aggregates. In a few tumours S-100 immunoreactivity occurred in the cytoplasm of tumour cells with or without cytoplasmic extensions. The presence of S-100 protein immunoreactive cells, apparently as an integral component, and its shape and distribution indicate that the peripheral nervous system (PNS) is histogenetically involved in the development of carcinoid tumours of the appendix.

Appendix↗

Neuron-specific enolase in mucosal endocrine cells and carcinoid tumours of the small intestine: a comparative study with neuron-specific enolase immunocytochemistry and silver stains.

Endocrine cells of human small intestinal mucosa, small intestinal carcinoids and carcinoid liver metastases were stained with an immunocytochemical technique using an antiserum against neuron-specific enolase (NSE), with the argyrophil technique of Grimelius and with the argentaffin technique of Masson. In the normal mucosa, scattered NSE-immunoreactive cells were seen mainly in the deeper parts of the crypts. These cells, as shown in the same sections, corresponded to the argentaffin and/or argyrophil cells indicating that they were of endocrine type. All intestinal carcinoids (16 cases) displayed NSE immunoreactivity. However, this reaction did not correlate on the cellular level with the silver techniques employed. Thus, many tumour cells were NSE immunoreactive but lacked an argentaffin or argyrophil reaction and vice versa. On the light microscopical level the silver techniques reveal the presence of neurohormonal granules in the tumour cells, while the NSE immunoreactivity appears to disclose neuroendocrine differentiation of the tumour cells irrespective of their hormone and granular content. Out of 13 carcinoid liver metastases, eight displayed strong NSE immunoreactivity, three were weakly stained and two were unreactive. Consecutive or the same tumour sections showed an argentaffin and argyrophil reaction in all carcinoid metastases. Since silver staining provides one type of information and NSE immunocytochemistry another, they provide in combination a good discriminator for neuroendocrine tumours.

Carcinoid Tumor↗

Nuclear DNA and endocrine activity in carcinomas of the breast.

In a running study of nuclear DNA profiles of female breast carcinomas, 60 consecutive tumors were collected and stained with the Grimelius argyrophil reaction for the identification of endocrine tumor cells. Four (6.7%) tumors were argyrophilic, and they all displayed diploid nuclear DNA values. The argyrophil tumors constituted 20% of the diploid breast carcinomas. One of the tumors was examined electron microscopically and exhibited an abundance of intracytoplasmatic granules of neurohormonal type. In none of the four carcinomas could the endocrine activity be inferred from the morphologic appearance alone, since all could be grouped in regular histopathologic terms. Since the frequency of endocrine cells in unselected materials of breast adenocarcinomas is very low, a relationship exists between diploid nuclear DNA values and with neurohormonal production in these tumors.

Breast Neoplasms↗

Small intestinal chromaffin cells and carcinoid tumours: a study with silver stains, formalin-induced fluorescence and monoclonal antibodies to serotonin.

The enterochromaffin cells of the human small intestinal mucosa were stained immunocytochemically with monoclonal antibodies against serotonin. The staining results were compared with those obtained with other methods for identifying serotonin-containing endocrine cells such as the argentaffin reaction, formalin-induced fluorescence and the argyrophil reaction of Grimelius. The different techniques gave similar, but not identical, results. The serotonin-immunoreactive cells outnumbered the argentaffin cells by 7%. Almost all (99%) serotonin-immunoreactive cells showed formalin-induced fluorescence but only a small population (5%) were fluorescent. In a subsequent study, these techniques were applied to 14 small intestinal carcinoids. It was shown that formalin-induced fluorescence and the argentaffin reaction were positive in 14 and 13 tumours, respectively, while the monoclonal serotonin antibodies failed to stain seven of the tumours. It is concluded that formalin-induced fluorescence and the argentaffin reaction are more useful techniques than serotonin immunocytochemistry for defining these tumours in routine formalin-fixed surgical specimens.

Carcinoid Tumor↗

Silver stains and immunocytochemical analysis with monoclonal serotonin antibodies for liver metastases of endocrine tumors. A study on percutaneous biopsy specimens.

With the aid of ultrasonography, representative percutaneous biopsy specimens were obtained from 20 of 21 patients (95 percent) with liver metastases of carcinoids and endocrine pancreatic tumors. The specimens were examined with silver stains and immunocytochemically after the application of monoclonal serotonin antibodies. The Grimelius argyrophil silver nitrate stain was positive in all tumor metastases, demonstrating that they were of neurohormonal endocrine type. The argentaffin reaction stained 14 of 15 metastases of small intestinal carcinoids, whereas tumors with other primary sites were unreactive. Immunocytochemical analysis with monoclonal serotonin antibodies stained all metastases of small intestinal carcinoids, and the other endocrine tumor metastases were unreactive. With immunocytochemical analysis, optimal results were obtained in Bouin-fixed tumor specimens, whereas for the argentaffin reaction, formalin was preferable. The results show that silver stains and immunocytochemical analysis with monoclonal serotonin antibodies on small percutaneous biopsy specimens of liver metastases of endocrine tumors and carcinoids are valid for the prediction of the location of the primary tumors.

Adolescent↗

Histopathology of gastric carcinoids: a survey of 42 cases.

An unselected series of 42 gastric carcinoids has been reviewed. Clinically the tumours simulated common gastric lesions including ulcer, polyp and carcinoma. No endocrine symptoms were identified. The tumours were most frequent in the body of the stomach and in 25% in that site were multiple. Morphologically most tumours when classified according to Soga (1974) demonstrated a mixed growth pattern. Six tumours displayed an atypical morphology (type D): they were larger and metastasized more frequently than the rest of the tumours. Six tumours contained a few scattered argentaffinic cells but the others were negative indicating negligible serotonin secretion in only a few cases. The Grimelius argyrophilic reaction was positive in most cells in all tested tumours except in three, two of which showed atypical morphology (type D). It is suggested that gastric carcinoids with a type D morphology or a minority cell population of argyrophil cells are dedifferentiated carcinoids which are biologically nearer to gastric carcinomas. The most frequent clinicopathological correlation was achlorhydria linking pernicious anaemia and gastric carcinoids. This indicates pathogenetic similarities between gastric carcinoids and gastric carcinomas.

Adult↗

Nuclear DNA record in a malignant rectal carcinoid. A case report.

A colo-rectal resection was performed on a 73-year-old woman with a preoperative diagnosis of rectal carcinoma. Morphological examination of the specimen revealed a rectal carcinoid tumor with regional lymph node and liver metastases. Silver stains demonstrated an argyrophil reaction in the tumor cells, but the argentaffin reaction and immunocytochemistry with monoclonal serotonin antibodies were negative. Imprint cytology of the tumor was examined cytofluorometrically and diploid nuclear DNA values were recorded with only few tetraploid cells (less than 2%.). It is suggested that diploid nuclear DNA values and a low proliferative activity are characteristic of malignant rectal carcinoids.

Aged↗