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Biomedical subjects

P G Lindgren

Publications and source records attributed to P G Lindgren.

At least 19 recordsLinked to original sources

N-myc gene amplification in neuroblastoma: a clinical approach using ultrasound guided cutting needle biopsies collected at diagnosis.

N-myc gene amplification was studied in a consecutive series of neuroblastomas and ganglioneuromas, representing all of such tumours diagnosed in Sweden over a 4-year period. Both frozen and formalin fixed specimens were used for Southern blot analysis. Thirty-seven of 46 neuroblastomas and 7 of 9 ganglioneuromas were analyzed. Seven neuroblastomas and none of the ganglioneuromas showed N-myc gene amplification. All children with amplified tumours, including three infants, had advanced disease at diagnosis and aggressive course of disease. However, follow-up time was short for the two cases still alive. The use of an ultrasound guided cutting needle biopsy technique for obtaining the required tissue at diagnosis was evaluated in some cases. This technique appeared to be safe and clinically useful since early prognostic information was obtained. Using an imprint from the needle biopsy, the representativity could be confirmed. Ultrasound guided cutting needle biopsies can thus be used routinely to obtain N-myc gene amplification data prior to initiation of therapy in neuroblastoma.

Biopsy, Needle

Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1.

In multiple endocrine neoplasia type 1 (MEN-1), benign enlargement of the adrenal cortex has been found in about one third of necropsy cases. To elucidate the clinical and genetic characteristics of the MEN-1 adrenal lesion, we have investigated 33 MEN-1 patients. Twelve individuals (37%) demonstrated adrenal enlargement, which was bilateral in 7 of them. Histopathology revealed diffuse and nodular cortical hyperplasia, adenomas, and a single case of adrenocortical carcinoma. The apparently benign adrenal enlargements were not associated with presently ascertainable biochemical disturbances in the hypothalamic-pituitary-adrenocortical axis, and they were without radiological signs of progression during follow-up. The individual developing unilateral adrenocortical carcinoma showed rapid adrenal expansion, feminization, and an abnormal urinary steroid profile after 4 yr of observation for bilateral minor adrenal enlargements. Pancreatic endocrine tumors were significantly overrepresented and present in all MEN-1 individuals with adrenal involvement. In agreement with findings in sporadic cases, the MEN-1 adrenocortical carcinoma genome showed loss of constitutional heterozygosity for alleles at 17p, 13q, 11p, and 11q. The benign adrenal lesions retained heterozygosity for the MEN-1 locus at chromosome 11 q 13. Despite its prevalence and malignant potential, the pituitary-independent adrenocortical proliferation does not appear to be a primary lesion in MEN-1, but might represent a secondary phenomenon, perhaps related to the pancreatic endocrine tumor.

Adrenal Cortex

Safety aspects and diagnostic findings of serial renal allograft biopsies, obtained by an automatic technique with a midsize needle.

Percutaneous biopsy is an important diagnostic procedure in evaluating the renal allograft with compromised function. Graft losses and haemorrhagic complication are major risks. To minimize these problems we used a midsize TruCut needle, controlled by an automatic firing device (Biopty-Cut), fixed to an ultrasound guidance system. Core biopsies of 1.2 x 20 mm were obtained from 1,421 kidney grafts. On 5 occasions a haemorrhagic complication that required prolonged hospitalization or intervention occurred. No grafts were lost as a consequence of the biopsy procedure. Typical histological morphological parameters found during allograft rejection has earlier been established. Using a protocol with 27 histological parameters this study confirms that recognized criteria for rejection can be relied upon even with this smaller needle. The results showed that the degree of oedema and lymphocytic infiltration of the interstitium and in the arterial wall discriminated best between rejecting grafts and non-rejection grafts.

Adult

Ultrasound guided tumour biopsy in the anterior mediastinum. An alternative to thoracotomy and mediastinoscopy.

To evaluate percutaneous ultrasound (US) guided tumour biopsy of the anterior mediastinum all patients scheduled for open mediastinal biopsy were considered for percutaneous biopsy during a 2-year period. US guided biopsy was chosen when CT had shown the tumour to be in contact with the thoracic wall. US guided biopsy was performed in 23 patients on 28 occasions. The procedure was technically successful in all cases and no complications occurred. In 27 of 28 cases the biopsy diagnosis was identical to the final diagnosis. In one patient with a malignant lymphoma a false diagnosis of connective tissue remnant was reached. US guided tumour biopsy of the anterior mediastinum is a safe, cost-effective and reliable method and a good alternative to the traditional biopsy techniques via mediastinoscopy or thoracotomy.

Adolescent

Ultrasound guided needle biopsy of brain tumors using an automatic sampling instrument.

All ultrasound (US) guided needle biopsies of brain tumors performed during an 8-year period were reviewed. Tissue samples were obtained in 112 of 115 biopsy procedures, and a histologic diagnosis was established in 99 cases (88.4%). The rate of major complications was 8.0%. The mortality is similar as in reports on stereotactic and CT-guided biopsy procedures while the morbidity is higher in our material. There are no large series available on US guided intracranial biopsy with adequate reports of complications. A modified biopsy technique is introduced here using a cutting needle and an automatic sampling instrument. The modified technique, which has been used in all cases since 1985, yielded diagnostic material in 91.5%. This method consistently provides a tissue core which is essential for a confident histopathologic diagnosis.

Biopsy, Needle

Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC): the clinical variation and prenatal diagnosis.

Six patients with the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, namely five members of the same family and one sporadic case, are presented. One of the main features of the EEC syndrome, ectrodactyly, was missing in five of the patients. The diagnosis did not become clear until the youngest son of the family was born. All of our six patients had a low birth weight and some were born preterm, and four had poly- and/or syndactyly without ectrodactyly. A low birth weight and polysyndactyly have been reported previously in patients with the EEC syndrome and might be features of the syndrome. The present patients illustrate the great phenotypic variability in the EEC syndrome and the need for a careful search for microsymptoms in potential gene-carriers. In two members of the affected family, EEC syndrome was diagnosed prenatally after 16 weeks of gestation by detection of the cleft lip and palate on ultrasound examination. The mother chose to continue the pregnancies. However, prenatal diagnosis of cleft lip and palate might be of value in genetic counselling for other inherited syndromes leading to severe disability.

Adult

Effects of interferon on tumor tissue content in liver metastases of human carcinoid tumors.

In 21 patients ultrasound-guided cutting biopsies, from carcinoid metastases of the liver, were taken before and after therapy with alpha-interferon. Each biopsy was examined under light microscopy and the amount of tumor tissue and connective tissue was quantified and then correlated to objective response to interferon therapy. A significant reduction of the amount of tumor tissue, in spite of unaltered metastatic size and a corresponding increase in connective tissue, was seen after interferon therapy. A more pronounced reduction of tumor tissue occurred after long-term interferon therapy. A positive correlation between objective therapy response and tumor tissue reduction was also present. Patients responding poorly, or not at all, to therapy did not show any significant decrease in tumor tissue. Since treatment with immune response modifiers is expected to increase in the near future, it is important to choose the right investigations for therapy monitoring, and since all patients in this investigation had unchanged tumor size on repeated radiological examinations, it is obvious that microscopic examination of core biopsies is a better method for evaluating effects of long-term therapy than tumor size measurement with radiological techniques. Further, the results may indicate that interferon exerts a cytotoxic effect on carcinoid tumor cells in vivo.

Adult

Neuroendocrine pancreatic tumours: clinical presentation, biochemical and histopathological findings in 84 patients.

A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 35 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominal symptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.

Adenoma, Islet Cell

Biopsy of the pancreas with a biopsy gun.

Cutting-needle biopsy under ultrasonic guidance was performed in 47 patients with suspected pancreatic carcinoma. The final diagnosis as revealed by autopsy, surgery, or radiologic/clinical follow-up was pancreatic malignancy in 39 patients and benign disease in eight. A correct diagnosis with the aid of biopsy findings was obtained in 44 of the 47 patients (94%). In three patients with carcinoma of the pancreas, the correct diagnosis was not obtained with use of results from the first biopsy. In two of these three patients, simultaneous biopsy of a liver metastasis revealed the presence of a malignant tumor growth. After the biopsy, two patients had a vasovagal reaction, and two experienced mild pain. No case of biopsy-induced pancreatitis occurred, although in one patient a transient rise in the serum amylase level was seen. The present results show that cut biopsy of the pancreas is a useful, reliable, and nontraumatic method in the diagnosis of pancreatic malignancy.

Adenoma, Islet Cell

Nuclear DNA distribution in neuroendocrine gastroenteropancreatic tumors before and during treatment.

The nuclear DNA contents of tumor cells in 73 patients with endocrine gastrointestinal tumors, 19 patients with endocrine pancreatic tumors (EPT) and 54 patients with malignant carcinoid tumors were determined before and after treatment. The DNA profiles were divided into diploid and aneuploid. In untreated patients, 9 out of 10 (90%) primary EPT and all 9 primary malignant carcinoid tumors (100%) were diploid. Tumor cell imprints from liver metastases of patients with untreated EPT showed aneuploidy in 5 of 11 cases, but only in 7 out of 46 DNA records from patients with untreated carcinoid liver metastases. DNA alteration from diploid to aneuploid profiles occurred in 2 patients with endocrine pancreatic tumors who had received chemotherapy. A change from diploid to aneuploid records was also seen in 7/23 (30%) carcinoid tumors after treatment. The DNA patterns before and after treatment did not show any correlation with survival or treatment response.

Adenoma, Islet Cell

Treatment of hormone-producing adrenocortical cancer with o,p'DDD and streptozocin.

Three patients with advanced adrenocortical carcinoma were treated with a combination of intermittent streptozocin and continuous o,p'DDD. Two patients were treated preoperatively and the primary tumors, initially considered as inoperable, could be resected after 19 and 5.5 months, respectively. In the patient with the longer treatment (35 months), lung and lymph node metastases disappeared and she has no evidence of recurrent disease 6.5 years after start of therapy. One patient was followed by magnetic resonance imaging (MRI) and urinary steroid secretion. The MRI gave a good visualization of the tumor. Measurements of relaxation times showed a significant decrease in T1 values. The urinary steroid profile showed an increased secretion of 3 beta-hydroxy-5-ene steroids and tetrahydro-11-deoxy-cortisol. Treatment with streptozocin and o,p'DDD initially increased 16-oxygenation of dehydroepiandrosterone and androst-5-en-3 beta,17 beta-diol, followed by a decrease in the secretion of all urinary steroids. The third patient received postoperative treatment with no effect on metastatic disease in the lungs, she died 9 months after start of treatment. The therapeutic approach with the combination regimen of streptozocin and o,p'DDD pretreatment plus aggressive surgery has to be further evaluated, as well as MRI and urinary steroid profile as methods to monitor the effect of therapy.

Adrenal Cortex

Improved myocardial protection by creatine phosphate in cardioplegic solution. An in vivo study in the pig during normothermic ischemia.

The effect of creatine phosphate in potassium cardioplegia was studied in a pig heart model in vivo. Fifteen pigs divided into two groups were placed on cardiopulmonary bypass and subjected to 1 hour of cardioplegic arrest at normothermia. In group I (control), in which a potassium cardioplegic solution was used, only two out of eight animals could successfully be weaned from bypass. In group II, on the other hand, in which creatine phosphate (10 mmol/l) was added to the cardioplegic solution, six out of seven animals could be weaned from bypass and the heart performance assessed by volume loading. Group II also exhibited better maintenance of high-energy phosphates during ischemia, with significantly higher adenylate charge potential, than group I. In all animals weaned from bypass--two in group I and six in group II--the ventricular performance was decreased compared with that before induction of ischemia. The results indicate that creatine phosphate could be an effective constituent in potassium cardioplegia.

Animals

Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival.

In a prospective study of 103 patients with carcinoid tumors consecutively referred for medical treatment, the most common sites of the primary tumors were the ileum (73%), bronchi (7%), and jejunum (4%). All patients had local metastases, and 96 (93%) also had liver metastases. The most common initial symptoms were diarrhea (32%), ileus (25%), and flush (23%). The overall frequency of diarrhea was 84% and of flush was 75%. Heart insufficiency caused by cardiac valve disease was seen in 33% of the patients. The carcinoid syndrome, including flush, diarrhea, and elevated urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations, was manifested by 69 patients (67%), 64 of whom (93%) had carcinoid tumors of mid-gut origin. Elevated urinary 5-HIAA was found in 91 patients (88%), of which 89 displayed liver metastases. The plasma concentration of the tachykinin neuropeptide K (NPK) was elevated in 67 patients (66%), 63 of whom had tumors of the mid-gut region. Serum pancreatic polypeptide (PP) and human chorionic gonadotrophin alpha levels were elevated in 43% and 28% of the patients, respectively, and the highest levels were found in patients with metastatic bronchial carcinoid tumors. Thirty-nine of the 103 patients are now dead; 18 died of tumor progression, whereas 14 patients died of heart failure secondary to a carcinoid tricuspidal valve insufficiency. The estimated median survival from the time of histologic diagnosis was 14 years, and from the time of carcinoid syndrome was 8 years.

Adult

Percutaneous ultrasonography-guided cutting biopsy from liver metastases of endocrine gastrointestinal tumors.

Ultrasonography-guided cutting needle biopsy of the liver was performed in 186 instances on 95 different patients with carcinoid and endocrine pancreatic tumors. In 171 cases, biopsy specimens were taken from liver metastases found on ultrasonography, and in 93% of these the obtained material was adequate for a correct diagnosis. In the 7% for which an incorrect diagnosis was made, all but one biopsy specimen contained normal liver tissue, indicating that the needle-guiding technique, and not the sampling technique, is the most critical part of the biopsy procedure. Tumor specimens were examined with silver stains and immunocytochemistry after application of monoclonal serotonin antibodies. The argyrophil silver stain of Grimelius could be applied on all specimens and had positive results in all but one case, demonstrating the neurohormonal endocrine origin of the metastases. The argentaffin reaction and/or serotonin immunoreactivity could be applied in 152 cases and had positive results in 115 of 122 (94%) of the mid-gut carcinoid tumors and negative results in 27 of 28 (96.4%) of the non-mid-gut carcinoid tumors and endocrine pancreatic tumors. Major complications occurred in 1.5%; none was lethal or required surgery. The results show that the technique used for tumor biopsy is very accurate and provides material sufficient for multiple histopathologic and immunocytochemical analyses without exposing the patients to high complication risks. It is further concluded that the staining techniques and immunocytochemical analyses applied on the biopsy specimens are valid for the prediction of the location of the primary endocrine tumor.

Adult