Evaluation of MMP-1, MMP-8, MMP-9 serum levels in patients with adrenal tumors prior to and after surgery.

The aim of the study is to evaluate MMP-1, MMP-8 and MMP-9 serum levels in patients with adrenal tumors prior to and after surgery. Metalloproteinase-1 (MMP-1), MMP-8 and MMP-9 serum levels were evaluated in 43 patients operated on at our clinic between 1997-1999. Forty-one (95.3%) patients underwent adrenalectomy. Two (4.7%) patients were disqualified from surgery due to infiltration of adjacent tissues. MMP-1, MMP-8 and MMP-9 serum levels were determined at the admission and in case of surgery again one month after the operation. ELISA assay (K&D) was applied. Tumor type was determined on the basis of clinical, hormonal and histopathological examination. The correlation between MMP levels and tumor sizes was also evaluated. Patients were divided into 6 groups. Group I included 11 patients with adrenocortical carcinoma (4 with Cushing's syndrome and 7 with incidentalomas); group II--6 patients with benign hormonally active adrenocortical adenoma (4 with Cushing's syndrome and 2 with Conn's syndrome); group III--patients with benign, hormonally inactive adenocortical adenoma; group IV--6 patients with benign, hormonally active phaeochromocytoma; group V--4 patients with hormonally inactive phaeochromocytoma; group VI--5 patients with hormonally inactive adrenal tumors of extraglandular origin (2 myolipomas, 2 fibrolipomas, 1 hammartoma). The control group comprised 10 healthy individuals. Increased MMP-8 and MMP-9 levels were noted in patients with benign and malignant adrenal tumors. No increase of MMP levels was found in patients with tumors of extraglandular origin. The increased MMP-8 and MMP-9 levels occurred most frequently in patients with adrenocortical and hormonally active adrenomedullar cancer, and most rarely in patients with hormonally active adrenocortical tumors. MMP-8 and MMP-9 serum levels did not significantly differ between patients with adrenocortical incidentaloma cancers and in patients with benign incidentalomas. MMP-8 and MMP-9 levels were not increased in patients with inoperable adrenocortical cancers. Serum MMP-1 levels were not increased in patients with benign and malignant adrenal tumors. After surgery, MMP-8 and MMP-9 levels decreased significantly in patients with adrenocortical cancers, whereas the decrease of these MMPs in patients with benign tumors, although noticeable, was not statistically significant. MMP-8 and MMP-9 levels decreased significantly in all patients with increased preoperative levels, although they remained higher than the maximum normal values only in few patients (in 7 and 2 patients, respectively). No correlation between the levels of evaluated MMPs and tumor sizes were found.

Medullary thyroid carcinoma (MTC)--clinical and molecular aspects on the basis of own experience.

In our clinic 19615 patients were operated over 25 years on for goiter. Malignant thyroid neoplasms were found in 1049 (5.3%) patients including 875 (83.4%) women and 174 (16.6%) men. Sixty two adult patients (42 women and 20 men were operated on for medullary thyroid carcinoma (MTC). Thyroid cancer was diagnosed in this group pre or intraoperatively in 44 (71%) patients and postoperatively, on histologic examination, in 18 (29%) patients. These patients were reoperated. Radical operations (total thyroidectomy with regional lymph node removal) were conducted in 43 (69.3%) patients and palliative ones in 19 (30.7%) patients. After MTC surgery, MEN 2A (MTC and an adrenal tumor) were diagnosed by means of imaging techniques (USG, CT) in 6 (9.7%) patients. All adrenal tumors were unilateral. Five of these patients were operated, and pheochromocytoma was confirmed by histopathologic examination. Two years after the MTC operation, 1 women was lost to follow-up. After a year, she was admitted to hospital for severe hypertension and died of cerebral hemorrhagia. Pheochromocytoma was revealed by autopsy. All patients were treated complementarily after the MTC operation. Different combinations of teleradiotherapy, chemotherapy and substitutive doses of levothyroxine were used. Ten (23.2%) of 43 patients operated radically were reoperated 1-3 years after the first operation due to loco-regional tumor recurrence. Radical reoperations were performed in 4 patients, and palliative ones in 6. Over a 0.5-23-year follow-up period, 26 (41.9%) patients died, including 20 of cancer, and 6 of other reasons. Four out of 36 living patients have clinical or biochemical symptoms of neoplastic disease. The follow-up period of MEN 2 patients operated on ranged from 1 to 6 years. Up to now, no tumor in the second adrenal gland has been diagnosed in any of these patients. Genetic (molecular) tests performed in 31 out of 36 living patients revealed mutations of RET gene in 4 (12.9%).

Colorectal carcinoid tumors--own experience.

Symptomatology, diagnostics and treatment problems in 5 patients with colorectal carcinoid are presented. From 1974 to 1999 in the Clinic of Endocrinological and General Surgery of the Medical University of Lódz, 3001 patients underwent surgery due to acute appendicitis and 431 for colorectal cancer. Among them, there were 5 patients in whom the histological examination revealed colorectal carcinoid. The carcinoids were localized in the appendix in 4 patients and in the left colon flexure in 1 patient. The mean age of these 5 carcinoid patients at the time of diagnosis was 38.4 years (range 18-72 yr). The female-to-male ratio amounted to 4:1. The symptoms of all 5 patients was not typical for carcinoid of the colon. In four surgery was performed for acute appendicitis and one patient complained of chronic obstipation and pain in the left epi- and mesogastrium. The double-contrast examination of the large intestine revealed tumor of the left colon flexure. Four carcinoid patients with the signs of acute appendicitis had emergency surgery. The carcinoid tumors were diagnosed microscopically after surgery only. In 3 of them the tumor extended beyond the appendix and a reoperation was performed. In one patient with the tumor of small diameter (5 mm) involving only the mucosa and submucosa a reoperation was not indicated. In 3 reoperated patients right hemicolectomy with regional lymphadenectomy was performed. The patient with the tumor of the left colon flexure diagnosed preoperatively underwent radical surgery with regional lymphadenectomy. The postoperative histological examination of the tumor confirmed carcinoid. No carcinoid metastases were found in lymph nodes of all studied cases. Until today, all 5 carcinoid patients are alive with no signs of local reccurrence or distant metastases over the 1-20 year follow-up period.

The surgical treatment of adrenal gland tumors--incidentaloma.

Analysis of 32 patients operated on because of accidentally discovered adrenal tumors "incidentaloma" is presented. In 12 of them there was subclinical hormonal activity, in 9 of them tumors turned out to be pheochromocytoma and 3 of them were cortex adenoma. There were 20 hormonally inactive tumors, in 5 of them there were malignant lesions (4 of the cortex and 1 of the medulla). For evaluation of hormonal activity of adrenal tumors evaluation of chromogranin A and cortisol serum blood level or urine free cortisol level is recommended. For precise localization of the tumor beside USG also CT examination is of use. According to the high percentage of malignant lesions in "incidentaloma" type tumors, surgery treatment without delay is recommended. BAC or DHES in blood serum examinations were not found helpful in preoperative evaluating the lesions as benign or malignant. In case of preoperatively found subclinical hormonal hyperactivity of medulla pharmacological treatment with alpha and beta blockers in surgery preparation is recommended. Lateral extraperitoneal access for adrenalectomy is considered safe and provides good operational view. Laparoscopic procedure because of high percentage of malignant lesions in this group of patients is not justified.

Human brain homeothermy during sleep and wakefulness: an experimental and comparative approach.

To date human brain temperature has not been measured exactly. Limited published data indicate it to be about 37.5 degrees centigrade, which surprisingly is 1.O degrees centigrade lower compared with placental mammals larger than the rat. Although the human brain is only 2 percent of body mass, it accounts for 20 percent of basal metabolism. Therefore, the removal of excess heat produced inside the brain is the main problem for its temperature regulation. The brain-arterial blood temperature difference in humans is probably twice that of larger mammals - 0.5 degrees centigrade. These two temperature factors play a crucial role for human brain homeothermy, particularly during motionless quiet waking and sleep. Low ambient temperature causes sleep deprivation. Moderate ambient heat allows sleep with negligible disturbances, and in humans induces sweating on the face and on the hairy (or bald) skin of the head. In passive hyperthermy human brain homeothermy depends on: (i) sweat evaporation from the skin surface of the face and whole head with face skin vasodilation, and (ii) enhanced venous return from the skin to the sinus cavernosus. This sinus is situated ventrally to the hypothalamus. Tympanic temperature reflects brain temperature fluctuations in humans.

Significance of cranial circulation for the brain homeothermia in rabbits. I. The brain-arterial blood temperature gradient.

The hypothalamic-arterial blood temperature gradient (THpr-TAC difference) was studied on 10 freely moving rabbits at ambient temperatures between 0 and 42 degrees Celsius. In cold environment, below 10 degrees Celsius the THpt-TAC gradient varied considerably, but some distinct correlations were found between vasomotor responses of the nasal mucosa and fluctuations of brain temperature, as well as between vasomotor responses of the ear pinnas and changes of the arterial blood temperature. Vasodilatation of the nasal mucosa or the ear pinna caused respectively a drop in brain temperature or in arterial blood temperature. Opposite changes were induced by vasoconstriction in those areas. Variations in THpt-TAC gradient resulted from oppositely directed vasomotor responses in the nasal mucosa and in the ear pinnas. At high ambient temperatures above 35 degrees Celsius thermal panting was accompanied by selective brain cooling with respect to the arterial blood. Blocking the heat loss from the nasal mucosa caused an increase of the THpt-TAC difference, and under these conditions brain temperature was determined solely by arterial blood temperature. The assumed mechanism of the selective brain cooling in rabbits is the exchange of heat through the neurocranial bottom, between the ventral brain and the spacious splanchnocranial venous lakes supplied with blood from the nasal mucosa.

Significance of cranial circulation for the brain homeothermia in rabbits. II. The role of the cranial venous lakes in the defence against hyperthermia.

Chronic experiments were conducted on five freely moving rabbits at ambient temperatures of 0-42 degrees Celsius. The influence of nasal mucosal thermal changes on the venous blood temperature inside the pterygoid plexus and on the temperatures at three intracerebral sites were investigated against the background of the carotid arterial blood temperature shifts. A correlation was found between: (i) the fluctuations in the nasal mucosal temperature reflecting its vasomotor responses, (ii) temperature shifts of the pterygoid plexus venous blood, and (iii) of the ventral brain. Mucosal vasodilatation caused parallel drops in both the plexal blood and brain temperatures. However, mucosal vasoconstriction was accompanied by increases in temperatures at those sites. Intracranial thermal shifts were independent of the arterial blood temperature changes. During motor activity in normothermia nasal mucosal vasoconstriction was present, and in that case brain temperatures exceeded arterial blood temperature. During rest, mucosal vasodilatation appeared and brain base cooled below the arterial blood temperature. During panting in dry heat, the brain base was cooler than the arterial blood by as much as 0.5 degree Celsius. The intensity of the selective brain cooling was directly proportional to deep body temperature. The blockade of the respiratory evaporation in heat elicited an increase of the plexal venous blood as well as brain temperatures above the arterial blood temperature. We conclude that the venous blood outflowing from the nasal mucosa exerts a cooling influence on the brain through the pterygoid plexus.

[Usefulness of a strain of mice with genetically determined audiogenic epilepsy as a model of experimental epilepsy]. / Przydatnosc szczepu myszy obciazonych genetycznie padaczka audiogenna jako modelu padaczki doswiadczalnej

Behavioural and bioelectric characteristics of epileptic seizures caused by acoustic stimulus in mice from the Swiss Albino Rb strain with genetically determined audiogenic epilepsy are presented. The value of this epilepsy model is emphasized stressing that the epileptogenic stimulus acts from a distance, causing no damage to the nervous system and no artifacts. Besides that, seizures can be provoked at a definite frequency and at arbitrarily chosen time. A disadvantage of the model is the necessity of provoking each seizure separately which causes that this model cannot meet one of the conditions of Jasper's definition concerning spontaneity of seizure development. With regard to the course of seizure it is emphasized that it is somewhat similar to human grand mal epilepsy representing the basic phases of seizure. Electrophysiological investigations carried out under conditions of long-term fully reproducible experiment demonstrated presence of very evident and rich electrocorticographic symptomatology of audiogenic epileptic seizure whose behavioural phases show a high correlation with phasic changes in bioelectric brain activity. The investigations carried out in sleep failed to demonstrate differences in the susceptibility to seizure development when the stimulus was applied in waking state or in any of both phases of sleep. This strain is useful to morphological ultrastructural, biochemical and possibly electrophysiological investigations.

[The diagnosis and operative treatment of solitary thyroid nodule: a prospective study]. / Diagnostyka i leczenie operacyjne pojedynczego guzka tarczycy--badanie prospektywne.

The aim of the paper is to evaluate the usefulness of pre- and intraoperative examination methods in the diagnostics of solitary thyroid nodules, as well as the assessment of the histologic structure of these nodules. From 1.12.1997 to 15.06.1998 in the Clinic of Endocrinological and General Surgery at the Medical University of Lodz, 102 patients were operated for a solitary nodule. The solitary nodule was diagnosed on the basis of the clinical and ultrasound examination. A fine needle aspiration biopsy (FNAB) was performed in all patients. During the operation the presence of the solitary nodule was confirmed on the basis of macroscopic examination. If malignancy was suspected on intraoperative macroscopic examination, intraoperative histologic examination was carried out. In 82 patients with the solitary nodule, the benign nodule was diagnosed on the basis of FNAB in 45 (54.9%) patients and malignant one in 8 (9.7%). Malignancy in the nodule (follicular tumour, Hürthle cell tumour, cellulae suspectae) was suspected in 29 (35.4%) patients--in this group the intraoperative histologic examination was conducted. On the basis of postoperative histologic examination a thyroid malignant neoplasm was detected in 18 (21.9%) of 82 patients with the solitary nodule. Finally, out of 18 thyroid cancers, 8 (44.4%) were recognised preoperatively (FNAB), 3 (16.7%) intraoperatively and 7 postoperatively. Since the incidence of malignancy in solitary thyroid nodules is high the authors suggest that their precise pre- and intraoperative diagnostics is necessary. The use of described diagnostic methods enabled to recognise malignancy in the solitary nodule and to perform a primary radical operation in 61.1% patients. On the basis of the obtained results it seems justifiable to search new diagnostic methods which enable better pre- and intraoperative differentiation of benign and malignant thyroid nodules.

[The treatment of solitary thyroid nodules in non-toxic goiter with 96% ethanol injections]. / Leczenie pojedynczych guzków tarczycy w wolu obojetnym iniekcjami 96% etanolu.

40 patients (39 women and 1 man) aged 13-66 years (mean 35.9 years) with solitary benign non-toxic thyroid nodule confirmed by clinical and hormonal examination, ultrasonography and fine needle aspiration biopsy, were treated with intranodular percutaneous 96% ethanol injection, performed under ultrasound guidance. There were 34 patients with solid nodule (including 4 patients) with solitary nodule in recurrent goitre after thyroidectomy) and 6 patients with cyst. The nodules were 7-60 mm (mean 31 mm) in diameter. 1 ml of ethanol was instilled per 1 cm3 of nodule tissue. 1-5 (mean 2.6) sessions were conducted at one month intervals. The early follow-up evaluation of the results (the evaluation of nodule size by means of clinical and ultrasound examination) was performed after 6 months, and the long-term one after 2 years since the last injection. A morphological evaluation was conducted according to the following scale: 1--nodule disappearance, 2--cicatricial nodule (solid structure in the ultrasonography and less than 0.5 cm in diameter), 3--nodule smaller by [symbol: see text] 50% of initial dimensions, 4--nodule smaller by < 50% of initial dimensions. A final follow-up evaluation revealed: nodule disappearance in 15 (37.5%) patients (Group 1), cicatricial nodule in 10 (25%) patients (Group 2), nodules smaller by [symbol: see text] 50% of initial dimensions in 7 (17.5%) patients (Group 3) and nodules smaller by < 50% of initial dimensions in 8 (20%) patients (Group 4). The results in Group 1 and 2 were defined as good (25 patients--62.5%), in Group 3 as satisfactory (17.5%) and in Group 4 as bad. The results of treatment of cysts and nodules in recurrent goitre were good or satisfactory. The following complications were observed: 1) pain during and after the injection in 29 (72.5%) patients, 2) subfebrile body temperature ap to 38 degrees C in 4 (10%) patients and fever up to 39 degrees C on the 1-st day after the injection in 2 (5%) patients, 3) ecchymosis in 1 (2.5%) patient, 4) temporary dysphonia in 2 (5%) patients, 6) temporary unilateral vocal cord paralysis and temporary Horner syndrome in 1 (2.5%) patient. It seems that percutaneous ethanol injection can be useful treatment method of solitary benign non-toxic thyroid nodules, both cysts and solid nodules, in patients who do not consent to surgical treatment or with contraindications to an operation.

[About changes in the structure of surgically treated goiter]. / O zmianach w strukturze operowanego wola.

On the base of our own goiter material treated surgically between 1974-1996, we compared incidence of various types of goiter and thyroid carcinoma in years 1974-1985 and 1986-1996. We stated statistically significant decrease of operated Basedow goiter and significant incidence increase of thyroid cancer. In given years frequency of incidence of differentiated and anaplastic thyroid carcinoma have been changed.

[Treatment of solitary toxic thyroid nodules with the use of percutaneous ethanol injections]. / Leczenie pojedynczych nadczynnych guzków tarczycy przezskórnymi iniekcjami etanolu.

Twenty women aged 18-76 years (mean 42 +/- 23 years) with solitary benign toxic thyroid nodule were treated with intranodular percutaneous 96%-ethanol injection, performed under ultrasound guidance. 1 ml of ethanol was instilled per 1 cm3 of nodule tissue. 2-5 (mean 3.1) sessions were conducted every month. The early follow-up evaluation of the results (the evaluation of nodule size by means of clinical and ultrasound examination) was performed in 6 months, and the long-term one in 2 years after last injection. A morphological evaluation was conducted according to the following scale: 1--nodule disappearance, 2--cicatricial nodule (solid structure and less than 0.5 cm in diameter), 3--nodule smaller by [symbol: see text] 50% of its initial dimensions, 4--nodule smaller by < 50% of its initial dimensions. A functional evaluation was carried out according to the following scale: I--permanent euthyroidism, II--permanent decrease of hyperthyroidism, III--no functional effect. A final follow-up evaluation revealed: nodule disappearance in 2 (10%) patients (Group 1), cicatricial nodule in 8 (40%) patients (Group 2), nodules smaller by [symbol: see text] 50% of its initial dimensions in 2 (10%) patients (Group 3) and nodules smaller by < 50% of initial dimensions in 8 (40%) patients (Group 4). The results in Group 1 and 2 were defined as good (50%), in Group 3 as satisfactory (10%) and in Group 4 as bad; and I--permanent euthyroidism in 16 (80%) patients, II--permanent decrease of hyperthyroidism in 1 (5%) patient, III--no functional effect in 3 (15%) patients. 2 patients in whom new nodules appeared and 1 patient with bad morphological and no functional treatment effects were operated on. A histological examination revealed haemorrhagic necrosis surrounded by fibrous tissue in removed nodules. The following complications were observed: 1) pain during and after the injection in 15 (75%) patients, 2) subfebrile body temperature in 3 (15%) patients and fever up to 39 degrees C on the 1-st day after the injection in 1 (5%) patient, 3) local ecchymosis in 1 (5%) patient, 4) temporary dysphonia in 1 (5%) patient. It seems that percutaneous ethanol injection treatment can be an useful treatment method of solitary benign toxic thyroid nodules in patients who do not give their consent to surgical or 131I treatment or with contraindications to an operation or radioiodine therapy.

[Strumectomy in children and adolescents--personal studies with 12,000 operations]. / Strumektomia u dzieci i mlodziezy--doswiadczenia wlasne obejmujace 12,000 operacji wola.

At the Surgery Clinic of the Endocrinology Institute in Lódz we operated 12 344 patients between 1974 and 1992 because of various types of goitre. Among these there were 295 children and adolescents, 2.4%- aged between 9-18 years: 268 girls (90.8%) and 27 boys (9.2%). The goitre was 9.9 times more frequent in girls than in boys. In adults the ratio was 8:1.