Survival of 231 cervical cancer patients, treated by radical hysterectomy, according to clinical and histopathological features.

PURPOSE OF INVESTIGATION: The purpose of the study was to estimate the five-year survival of cervical cancer patients after radical hysterectomy, taking into account clinical data and histopathological parameters. METHODS: 231 patients with invasive cervical carcinoma were diagnosed, surgically treated--Piver III--and followed-up. Histological examination of specimens was performed according to the British NHS-CSP guidelines. RESULTS: We discovered no statistical significance as regards age at diagnosis, age at menarche and menopause, and number of pregnancies, deliveries and abortions, in relation to survival. We concluded that the clinical stage according to FIGO classification influenced survival. Statistical significances were: Ia2 vs Ib, Ib vs IIa and IIa vs more advanced than IIa. The following histopathological parameters correlated with survival: depth of cervical invasion, primary lesion volume, and parametrial, uterine, vaginal and lymph node involvement. Using Cox's proportional hazards model we found that only lymph node status and FIGO staging were independent parameters correlating with survival and mortality risk in our study. CONCLUSION: Prognostic indexes classifying patients at specific disease stages into different categories of risk should be based on histopathological features listed above. Such indexes are yet to be validated in larger, prospective studies conducted in different patient populations.

HPV and histological status of pelvic lymph node metastases in cervical cancer: a prospective study.

AIMS: The purpose of this prospective study was to describe the incidence and distribution pattern of human papillomavirus (HPV) DNA in intraoperative dissected lymph nodes and to relate this to the pathological confirmation of metastasis. METHODS: Samples of primary cervical cancer lesions and dissected lymph nodes were obtained from women undergoing surgical treatment. The presence of HPV DNA was detected by the polymerase chain reaction. RESULTS: Tissue from 79 tumours and 365 lymph nodes was analysed. Metastasis to the lymph nodes was found in 19 cases. Metastasis correlated with the volume of the primary lesion, the depth of cervical and vaginal invasion, and with invasion of the corpus. HPV DNA was found in 60 of the primary lesions and 31 of the lymph nodes. The presence of HPV DNA in the lymph nodes correlated with the volume of the primary lesion and vaginal invasion. CONCLUSIONS: The incidence of HPV DNA in lymph nodes is twice as high as that of histopathologically confirmed metastases. The risk of the presence of HPV DNA and histopathologically confirmed metastases in lymph nodes is related to certain features of the primary tumour.

[Elevation of serum Ca 15-3 antigen: an early indicator of distant metastasis from breast cancer. Retrospective analysis of 733 cases]. / Wzrost stezenia antygenu CA 15-3 w surowicy--wczesny wskaznik przerzutów odleglych raka piersi: retrospektywna analiza 733 chorych.

UNLABELLED: Aim of study was to summarize six-year institutional experience with serial evaluation of circulating CA15-3 antigen as a method of early detection of breast cancer relapse. MATERIAL AND METHODS: CA15-3 concentrations were assayed immuno-enzymatically in the sera of 733 women with breast carcinoma: in 707 cases marker was analyzed serially (every 4 months during follow-up after completion of radical treatment and when the relapse of breast cancer was clinically suspected) and in 26 patients--at diagnosis of locoregional relapse and\or breast cancer dissemination; 5493 assays of the CA15-3 antigen were performed in total. The cut-off limit was established at 30 u/ml. Results of CA15-3 tests were analyzed in relation to clinical status of the disease and dominant site of breast cancer relapse. RESULTS: 1) in patients with distant metastases (N = 149), mean serum CA15-3 values and the percentage of positive results were significantly higher as compared to cases with locoregional relapse and carcinoma of the contralateral breast (N = 54; p < 0.0001) and those without clinical evidence of relapse (N = 530; p < 0.0001), in agreement with previous studies; 2) the highest mean values of CA15-3 were observed in patients with liver and multiple metastases, lower in those with bone or lung secondaries, and the lowest when the metastatic involvement of supraclavicular nodes was noticed; 3) the CA15-3 sensitivity rates were higher in patients with liver or bone metastases (91.7% and 91.4%, respectively), as compared to those with multiple (79.5%) and lung (72.4%) secondaries, and the lowest when metastases in supraclavicular nodes (40.0%) or other organs (60.0%) were diagnosed; 4) the comparison of subjects with liver secondaries and those with other sites of breast cancer dissemination indicated statistically significant difference in the mean CA15-3 values (p < 0.0001) and the number of positive results of the test (p < 0.05); 5) the sensitivity rates of CA15-3 antigen for one, two, three and more skeletal metastases detected by bone scintigraphy were 50%, 100% and 100%, respectively (N = 30); 6) in 84 out of 116 (72.4%) patients with distant metastases, the increased CA15-3 concentration preceded the clinical diagnosis of the relapse with the median lead time 9 months (range: 1-40); 7) the highest positivity rates of the lead time were observed in patients with liver or lung metastases (93.8% and 81.0%, respectively) and the lowest one in those with multiple sites of metastases (43.0%). CONCLUSION: The study confirmed the validity of serial CA15-3 assays in the early diagnosis of breast metastatic disease. It is worth to emphasize the high sensitivity of the CA15-3 test in detecting bone metastases (100% in patients with scintigraphically diagnosed two or more metastatic lesions), but the group of patients was too small to make our observation conclusive. In none of the studies published previously, the beneficial impact of serial CA15-3 assays during follow-up on survival and quality of life in breast cancer patients was clearly demonstrated. Thus, modifying treatment based solely on increasing marker levels is not recommended.

Endometrial cancer in patients with breast carcinoma treated with tamoxifen: report of two cases and the literature overview.

Tamoxifen (TAM) is the endocrine treatment of choice in the first-line therapy for all stages of breast cancer, in both pre- and postmenopausal women. Some clinical studies indicated a small but significant increase in the risk of subsequent endometrial carcinoma in breast cancer women who take TAM as an adjuvant therapy. In this study, we present two cases of breast cancer patients in whom endometrial cancer was diagnosed during TAM treatment; the current status of knowledge on the relationship between TAM use and the risk of endometrial cancer is reviewed.

[Contraception and pregnancy in severe systemic lupus erythematosus: a case report]. / Antykoncepcja i ciaza u pacjentki z ukladowym toczniem trzewnym o ciezkim przebiegu--opis przypadku.

Systemic Lupus Erythematosus (SLE) during pregnancy may cause serious complications in the mother and fetus. We report a case of pregnancy in 23 years old woman with SLE. Pregnancy was complicated with spontaneous abortion and septic shock. Furthermore in our paper we discussed contraceptive methods proper for women with SLE. The choice of an optimal contraceptive method (OC) therapy is a significant problem in female SLE patients. In view of the influence of sex hormones on the evolution of SLE, oral contraceptive (OC) therapy has to be efficient, reversible and safe, without aggravating disease activity and causing metabolic and vascular side effects. As regards oral contraceptives, all authors agree that oestrogen-progestin combination pills are harmful, but the best alternative hormonal contraception remains to be determined. The management of the case and the review of current literature are presented. Our experience demonstrates the importance of interdisciplinary care.

Lysine14galanin(1-15)-NH2: a partial agonist at galanin receptors in rat isolated gastric fundus.

The study was undertaken to characterize the effects of the porcine galanin [pGal(1-29)-NH2] analogue [Lys14]pGal(1-15)-NH2 on rat gastric fundus. [Lys14]pGal(1-15)-NH2 is a less potent contractile agent than pGal(1-29)-NH2 (EC50 74.1 vs. 43.7 nmol/l, respectively) and shows a significantly lower maximal response than pGal(1-29)-NH2. Concentration-contraction curves were constructed for pGal(1-29)-NH2 alone (control) and pGal(1-29)-NH2 in the presence of 10, 100, and 1,000 nmol/l of [Lys14]pGal(1-15)-NH2. [Lys14]pGal(1-15)-NH2 shifted the concentration-contraction curves of pGal(1-29)-NH2 significantly to the right, whereas their linear portions remained parallel to that for the pGal(1-29)-NH2 control. [Lys14]pGal(1-15)-NH2 markedly increased the EC50 of the respective pGal(1-29)-NH2 concentration-contraction curves. It did not substantially change the maximal response of the muscles to pGal(1-29)-NH2 and the form of the respective concentration-contraction curves. Schild's plot gave a straight line with a slope of 0.84. The pA2 value for [Lys14]pGal(1-15)-NH2 was 8.23. [Lys14]pGal(1-15)-NH2 seems to be a partial Gal receptor agonist. Since the lack of specific Gal receptor antagonists in the gastrointestinal tract makes a precise characterization of its role as a motility modulator difficult, the position 14 in the pGal(1-29)-NH2 molecule looks as an attractive target in the search of a pure Gal receptor antagonist in the smooth muscles of the gut.

Contractile effects of porcine galanin(1-29)-NH2 on the rat isolated gastric fundus: mediation by potassium ions.

Galanin (3-300 nM) evoked reproducible concentration-dependent contractions of rat isolated gastric fundus strips, EC50 of the peptide equalled 16.7 nM (6.2-39.2) and the slope of the concentration-response curve was 34.8 (24.0-45.7). The maximal response (Emax) to carbachol (30 nM) was not affected by the absence of the potassium ions in the bathing solution. On the contrary the Emax to galanin (300 nM) was decreased by almost 95% by the use of the potassium-free buffer. Re-exposure of the muscle strips to potassium containing bathing medium reversed the inhibition by about 35%, yet the value remained significantly lower than that of the control. Apamin (1 and 2 microM), glybenclamide (10 microM), clofilium tosylate (10 microM) did not significantly influence the Emax to carbachol. Apamin or glybenclamide did not affect the contractile action of galanin, while clofilium attenuated the Emax to the peptide in a concentration-dependent manner, the EC50 of the agent being 9.44 microM (164 nM-541 microM). It was concluded that the potassium ions play a modulatory role in gastric smooth muscle contraction following galanin receptor stimulation, probably by interacting with the extracellular calcium influx.

Galanin, galantide and galanin (1-14)-[alpha-aminobutyric acid8]-scyliorhinin-I: structure dependent effects on the rat isolated gastric fundus.

The study was undertaken using selected pharmacodynamic parameters to describe the effects of porcine galanin(1-29)-NH2; porcine galanin fragments; galantide; porcine galanin(1-14)-[alpha-aminobutyric acid8]scyliorhinin-I and the analogues of the latter peptides on rat isolated gastric fundus muscle. All tested peptides, apart from galanin(16-29)-NH2 evoked reproducible concentration-dependent contractions with significantly decreased activities in comparison to the potency of the native galanin(1-29)-NH2 molecule. The order of the contractile ability in the group of galanin(1-29)-NH2 short fragments was as follows: [lysine14]galanin(1-15)-NH2 > galanin(1-15)-OH > galanin(1-15)-NH2 > [glycine5] galanin(1-15)-NH2 > galanin(2-15)-NH2 > [glycine5,lysine14]galanin(1-15)-NH2. Aside from [lysine14]galanin(1-15)-NH2 which had a lower efficacy, none of the peptides showed significant changes in this respect in comparison to the intact galanin(1-29)-NH2 molecule. The concentration-response curves of the tested peptides were to the right and their slopes besides from: galanin(1-15)-OH; galanin(2-15)-NH2; [glycine5]galanin(1-15)-NH2 remained not significantly different from galanin(1-29)-NH2. Hill's coefficient for galanin(1-29)-NH2 is 1.03 indicating an interaction of one galanin(1-29)-NH2 molecule with one receptor, fulfilling criteria of classical receptor theory. For galanin fragments Hill's coefficients are < 1 implying that the rules of classical theory may not apply. Galantide and analogues exhibited a subsequent decrease in potency: [cycloleucine4] galantide > galantide > [homoserine6]galantide > [phenylalnine(4fluor)17] galantide. Galanin(1-14)-[alpha-aminobutyric acid8]-scyliorhinin-I and its analogues contracted the gastric fundus with a decline in strength: galanin(1-13)-[norleucine10]-scyliorhinin-I(3-10) > galanin(1-13)-[phenylalanine(4fluor)7]-scyliorhinin-I > galanin(1-14)-[alpha-aminobutyric acid8]-scyliorhinin-I > galanin(1-13)-[alpha-aminobutyric acid8, norleucine10]-scyliorhinin-I(3-10). They all displayed a greater efficacy than galanin(1-29)-NH2, and the concentration-response curves were slightly to the right, almost parallel to that of galanin(1-29)-NH2. Slopes of the curves were not significantly different from galanin(1-29)-NH2. Hill's coefficient for the galantide, [cycloleucine4]galantide; [homoserine6]galantide; [phenylalanine(4fluor)17]galantide and galanin(1-13)-[phenylalanine(4fluor)7]-scyliorhinin-I are < 1. Hill's coefficients for galanin(1-13)-[norleucine10]-scyliorhinin-I(3-10); galanin(1-14)-[alpha-aminobutyric acid8]-scyliorhinin-I; galanin(1-14)-[alpha-aminobutyric acid8, norleucine10]-scyliorhinin-I(3-10) are > 1. A Hill's coefficient markedly different from 1 might indicate that an activation of more than one type of receptors, negative or positive receptor cooperativity or multiple-step agonist-receptor reaction.

Pharmacological characterization of the contractile effects of galanin (1-29)-NH2, galantide and galanin (1-14)-(alpha-aminobutyric acid8)scyliorhinin-I in the rat gastric fundus.

Porcine galanin (1-29)-NH2, galantide (M15) and galanin (1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I used in concentrations of 300, 1,000 and 3,000 nM respectively caused contractions of rat fundus strips. The contractile responses to galanin(1-29)-NH2 were not modified by atropine (10 microM), guanethidine (10 microM), naloxone (1 microM), a mixture of propranolol (10 microM) and phentolamine (10 microM), indomethacin (10 microM), a mixture of mepyramine (10 microM) and cimetidine (10 microM), saralasin (10 microM), and spantide (100 microM). The effects of M15 and galanin(1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I were significantly decreased by atropine for 36 and 18% and by spantide for 37 and 26% respectively. Indomethacin inhibited the muscle response to M15 without influence on the galanin (1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I-induced action. These results support findings that galanin (1-29)-NH2 contracts rat gastric fundus strips by stimulating specific receptors localized on the surface of smooth muscle cells. M15 and galanin(1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I seem to contract smooth muscles not only by acting at galanin receptors, but by interacting with muscarinic or tachykinin receptors or modulating the release of acetylcholine and substance P. Diltiazem (EC50 825 nM), dantrolene (EC50 30.2 microM) and the phospholipase C inhibitors U-73122 (EC50 549 microM) and U-73343 (EC50 751 microM) lowered the contraction to galanin(1-29)-NH2 in a concentration-dependent manner. These observations imply that though the extracellular Ca2+ influx plays a major role in the action of galanin(1-29)-NH2, the release of Ca2+ ions from the intracellular stores contributes to the response of smooth muscles of galanin(1-29) NH2. Norepinephrine (30, 60, 100 and 300 nM) concentration-dependently reduced the Emax to galanin (1-29)-NH2 and reduced the slopes of the concentration-contraction curves, without a notable change in EC50. Pertussis toxin pre-treatment (10 and 30 mg/kg intravenous [i.v.]), 120 h before the experiment, notably increased the maximal response of the rat gastric fundus to galanin(1-29)-NH2, without a significant change in the properties of the concentration-contraction curves (EC50, slopes). The observations may suggest that pertussis toxin-sensitive GTP-binding proteins are involved in the modulation of the excitatory effects of galanin(1-29)-NH2 in the rat gastric fundus.

Contractile action of galanin analogues on rat isolated gastric fundus strips is modified by tachyphylaxis to substance P.

This study was undertaken to characterize the interaction of porcine galanin (Gal) and some of its analogues with their receptors on rat gastric fundus muscle strips. Gal, galantide (M15) and Gal(1-14)-[Abu8]SCY-I evoked concentration-dependent contractions of gastric smooth muscle strips. Reproducible effects were observed in concentrations of 1-300, 3-1000 and 100-3000 nM, respectively. Specific EC50 for the contractile effect equalled 13.70 and 187 nM. Hill's coefficient for Gal is 1.03 indicating an interaction of one Gal molecule with one receptor, fulfilling the criteria of classical receptor theory. For M15 and Gal(1-14)-[Abu8]SCY-I Hill's coefficients are different from 1, namely 0.73 and 1.56, pointing out that the principle of interaction of one drug molecule with one receptor may not apply. The contraction induced by 300 nM of Gal was not significantly modified by tachyphylaxis to substance P (SP). On the contrary the introduction of tachyphylaxis to SP decreased the contractile effects of M15 and Gal(1-14)-[Abu8]SCY-I by about 57.7 +/- 3% and 39.6 +/- 5%, respectively. The findings suggest that contractile actions of M15 and Gal(1-14)-[Abu8]SCY-I are probably not only due to their agonist activities at Gal receptors but may result from a subsequent stimulation of receptors for SP or release of endogenous SP.

Actions of galanin and some of its analogues on rat isolated gastric fundus.

The study was undertaken to characterize the effects of porcine galanin (pGal) and some of its analogues on rat gastric fundus muscle strips. pGal, galantide (M15) and pGal(1-14)-[Abu8]SCY-I evoked reproducible concentration-dependent contractions in concentrations of 1-300, 3-1,000 and 100-3,000 nM, respectively, with EC50 values of 13, 70 and 187 nM. Hill's coefficient for pGal is 1.03, indicating an interaction of one pGal molecule with one receptor, fulfilling criteria of classical receptor theory. For M15 and pGal(1-14)-[Abu8]SCY-I, Hill's coefficients are significantly different from 1, namely 0.73 and 1.56, so that one drug molecule may not interact with one receptor. The stimulatory effects of pGal were not modified by dibenamine 10 microM or glybenclamide 1 or 10 microM. Diltiazem 0.1, 1 and 10 microM, papaverine 0.1, 10 microM or dibutyryl cAMP (dib cAMP) 100 and 300 microM, blocked the contraction to pGal in a concentration-dependent manner, indicating an important role for the influx of extracellular calcium ions and regulation by cAMP the pGal-evoked contraction. Diltiazem, dibutyryl cAMP and papaverine were not competitive antagonists of pGal in the stomach smooth muscle.

Desensitisation of substance P decreases the contractile effect of M15 and Gal (1-14)-(Abu 8) SCY-I on the rat gastric fundus.

Tachyphylaxis to SP decreased the effect of M15 and Gal(1-14)-[Abu8]SCY-I on gastric smooth muscles, without effect on the action of Gal. These findings support our initial hypothesis: the action of M15 and Gal(1-14)-[Abu8]SCY-I on the smooth muscles may not only be due to their agonist activity at Gal receptors, but may result from a subsequent stimulation of receptors for SP and perhaps for other tachykinins as well, however, a possibility that Gal analogues release endogenous SP can not be excluded. Further studies involving a tachykinin antagonist (spantide) are in progress at the moment. [1].