Cross my heart: ventriculoatrial shunt migration into the pulmonary arteries.

We present here a rare complication of ventriculoatrial shunt: migration of the distal catheter into both pulmonary arteries. The patient showed no cardiorespiratory symptoms. The catheter was removed by endovascular technic, the most usual procedure in these cases.

Decompressive craniectomy for encephalitis with brain herniation: case report and review of the literature.

BACKGROUND: Decompressive craniectomy (DC) has been sporadically used in cases of infectious encephalitis with brain herniation. Like for other indications of DC, evidence is lacking regarding the beneficial or detrimental effects for this pathology. METHODS: We reviewed all the cases of viral and bacterial encephalitis treated with decompressive craniectomy reported in the literature. We also present one case from our institution. These data were analyzed to determine the relation between clinical and epidemiological variables and outcome in surgically treated patients. RESULTS: Of 48 patients, 39 (81.25 %) had a favorable functional recovery and 9 (18.75 %) had a negative course. Only two patients (4 %) died after surgical treatment. A statistically significant association was found between diagnosis (viral and bacterial encephalitis) and outcome (GOS) in surgically treated patients. Viral encephalitis, usually caused by herpes simplex virus (HSV), has a more favorable outcome (92.3 % with GOS 4 or 5) than bacterial encephalitis (56.2 % with GOS 4 or 5). CONCLUSIONS: Based on this literature review, we consider that, due to the specific characteristics of infectious encephalitis, especially in case of viral infection, decompressive craniectomy is probably an effective treatment when brain stem compression threatens the course of the disease. In patients with viral encephalitis, better prognosis can be expected when surgical decompression is used than when only medical treatment is provided.

Changes of bone turnover markers and serum PTH after night or morning administration of zoledronic acid in breast cancer patients with bone metastases.

Persistent circadian rhythm of bone turnover in bone metastatic breast cancer suggests greater skeletal retention of bisphosphonates if administered in the night. We assessed differential effects of night vs morning administration of zoledronic acid (ZA) on bone turnover. Forty-four breast cancer patients with bone metastases were randomised to receive intravenous ZA (4 mg) at 1100 or 2300 hours every 28 days for four times. Urinary concentration N-telopeptide of type-I collagen (NTX) and deoxypyridinolines, and serum C-telopeptide of type-I collagen (CTX), bone alkaline phosphatase (ALP), osteocalcin and Parathyroid hormone (PTH) was measured in the morning at baseline and after 4, 7, 14, 28, 56 and 84 days. Urinary ZA concentration was also measured. Zoledronic acid caused significant decreases of NTX and CTX (P<0.001), without any difference in percent changes between night and morning arms. Bone ALP and osteocalcin were also significantly affected by ZA (P=0.001), without any difference between arms. Parathyroid hormone significantly increased in both the arms; PTH increase was lower in the night arm (P=0.001). From the second administration onwards, urinary ZA level was significantly higher in the night arm (P<0.01). Administration of ZA at two opposite phases of the circadian cycle causes similar changes of bone-turnover marker levels, but has differential effects on the level of serum PTH.

Association of cyst type with risk factors for breast cancer and relapse rate in women with gross cystic disease of the breast.

The concentration of potassium (K+) and sodium (Na+) was measured in breast cyst fluid (BCF) from 611 cysts greater than 3 ml aspirated in 520 women with gross cystic disease of the breast. These women were enrolled, from 1983 on, in a cohort study aimed at assessing the relationship between cyst type, as defined by the K+/Na+ ratio in BCF, and the risk of breast cancer. The inverse relationship between K+ and Na+ and the bimodal distribution of the K+/Na+ ratio in BCF were confirmed. Type I cysts were defined as cysts with a K+/Na+ greater than 1.5 in BCF. Among women with type I cysts, a higher proportion of women with one or no births, of women with a history of apocrine cysts, of current smokers, and of women who do not drink coffee was found, as compared to women with other types of cysts. The risk of cyst relapse was significantly higher among women with type I cysts than among women with other types of cysts and among women with multiple cysts at presentation. These findings indicate that type I BCF is a marker of "active" gross cystic disease of the breast and suggest that it may be associated with increased breast cancer risk.

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease.

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy. At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0-141.0) U/l at baseline, 19.1 (3.0-486.0) U/l after 3 months, 20.8 (3.0-702.0) U/l after 6 months and 39.4 (3.0-414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005). Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.

Comparison between two methods in the determination of circulating chromogranin A in neuroendocrine tumors (NETs): results of a prospective multicenter observational study.

Several methods for analyzing CgA using either monoclonal or polyclonal antibodies have been developed, which differ in their diagnostic performance. The present paper describes the results of a prospective multicenter study aimed at comparing the clinical value of the two most widely used commercially available CgA assay kits in patients affected by neuroendocrine tumors (NETs). Two hundred sixty-one patients from 40 different centers and 99 healthy subjects were evaluated. CgA levels were measured with two different methods, a two-step immunoradiometric assay (IRMA) and an enzyme-linked immunosorbent assay (ELISA). CgA was measured centrally by two reference laboratories, one of which used IRMA and the other ELISA, and it was measured by the participating institutions with the method routinely used by each of them. The major findings of the present study were: (i) the two assays for the determination of CgA present good diagnostic performance; (ii) both assays are robust and guarantee comparable results when applied in different settings (central vs local laboratory); (iii) the negative/positive cutoff points (87 ng/mL for IRMA and 21.3 U/L for ELISA) were established according to standardized criteria; (iv) the results obtained with the two assays in basal clinical samples of patients affected by NETs show an apparently satisfactory correlation (rs = 0.843, p < 0.0001). However, a possibly clinically meaningful 36% discordance rate was found. These findings support the hypothesis that the two CgA kits might provide partially different information.

Prognostic value in predicting overall survival of two mucinous markers: CA 15-3 and CA 125 in breast cancer patients at first relapse of disease.

The role of circulating tumour markers in providing prognostic information has been scarcely studied. We evaluated the prognostic significance of two mucinous markers: CA 15-3 and CA 125 in 115 breast cancer patients at first recurrence of disease. At diagnosis of advanced disease bone involvement was found in 64 patients, lung in 57, skin lymph nodes in 21, liver in 20, and brain in 5. Patients were recruited and treated in the same institution with conventional chemo- or endocrine therapy. The follow-up ranged from 3 to 54+ months (median 35). Serum samples were drawn at first recurrence of disease before the start of any endocrine and/or chemotherapy. Patients with CA 15-3 < 30 U/ml survived significantly longer than those with CA 15-3 > 30 U/ml (median 50+ versus 26 months, P < 0.02). Similarly, overall survival of patients with CA 125 < 35 U/ml was significantly higher in comparison with patients with CA 125 > 35 U/ml (median 34.5 versus 18.5 months, P < 0.001). CA 125, but not CA 15-3, maintained its prognostic value in the subgroup of patients with visceral metastases. Both markers were found to be independent prognostic variables in multivariate analysis according to Cox's model. CA 15-3 and CA 125 appeared to be powerful prognostic indicators, in addition to visceral metastases, in patients with advanced breast cancer.

Wolfe's mammographic patterns in women with gross cystic disease of the breast.

The epidemiologic determinants of the mammographic pattern were studied in 710 patients with aspirated gross (> 1 ml) cysts of the breast. The prevalence of the mammograms classified as P2-DY, that are considered to be associated with an increased breast cancer risk, was 636/710 or 89.6%. No relationship between mammographic patterns and characteristics of breast cyst fluid such as K+/Na+ ratio, apocrine changes and dehydroepiandrosterone sulfate concentration was observed. A significant decrease in the proportion of these patterns with increasing age (p = 0.006), Quetelet Index (p < 0.001), parity (p = 0.001), and in postmenopausal women (p = 0.026) was found. Conversely, P2-DY patterns were significantly associated with a later age at menarche (p = 0.023) and alcohol consumption (p = 0.001). In multivariate analysis, an independent association with age was not observed whereas the associations with age at menarche, parity, and relative weight were confirmed. In conclusion, the epidemiologic determinants of mammographic patterns are the same in Gross Cystic Disease patients as in unaffected women, and the lack of correlation between mammographic pattern and cyst type suggests that the latter may represent an independent predictor of breast cancer risk.

Steroid biochemistry and categorization of breast cyst fluid: relation to breast cancer risk.

Patients bearing macrocysts of the breast are at higher risk of later developing cancer. The fluid filling the cysts (breast cysts fluid, BCF) contains unusual amounts of steroid conjugates, first androgen and estrogen sulfates. Measuring BCF cations (K+,Na+) allows categorization of cysts into two major subsets (type I and type II) that are associated with a different degree and/or turnover of apocrine metaplastic cells in the lining epithelium. Type I cysts (high K+/Na+ ratio) accumulate hugh amounts of dehydroepiandrosterone sulfate, estrone sulfate, androstane-3 alpha,17 beta-diol glucuronide, androsterone glucuronide and contain more testosterone and dihydrotestosterone than type II. Conversely, type II cysts (low K+/Na+ ratio) contain more progesterone and pregnenolone. A cohort study was started in 1983 at the Cancer Prevention Center, Ravenna, Italy, with the aim of evaluating the relationships between the biochemistry of BCF and the incidence of breast cancer in women with gross cystic disease (GCD) of the breast. The bimodal distribution of the cationic pattern has been confirmed from data obtained in 798 patients aspirated. The risk of cyst relapse was significantly higher among women with type I cysts or with multiple cysts at presentation. Twelve incident cases of breast cancer have been diagnosed among women whose BCF was categorized. Eleven out of 12 cases had type I or multiple cysts. The cumulative incidence of breast cancer among patients bearing type I cysts was 2.5%. We conclude that women with GCD bearing type I cysts have an increased breast cancer risk when compared with the counterpart bearing type II cysts or the general population.

Melatonin and human cancer.

A number of studies performed in vitro and on experimental animals supported the view that pineal gland inhibits neoplastic growth. Data in humans are scanty and controversial. In the present study we measured serum melatonin (MT), prolactin (PRL) and growth hormone (GH) concentrations, at 08.00 and 24.00, in 132 cancer patients and in 58 healthy control subjects. The patients were stratified according to histology and stage of disease as follows: 30 stage I-II and 45 stage III-IV breast cancer (BC); 39 stage III-IV lung cancer; 18 advanced gastrointestinal (GI) cancer. We also measured MT levels, at the same time-points, in 20 women with primary BC before and after radical mastectomy. Finally, we evaluated the circadian rhythm of serum MT in 18 patients with advanced cancer. On the whole, the patients with advanced tumors showed serum MT levels significantly higher than controls, without any correlation with PRL and GH values. When looking at stage III-IV vs stage I-II BC patients, significantly higher MT levels have been found in the former group. The surgical removal of the primary BC was not associated with any changes in MT values at both time points considered. A highly significant rhythm of serum MT was recorded in advanced cancer patients and the rhythmic parameters were substantially superimposable on those of the control subjects.

Biochemical picture of bone metabolism in breast cancer patients with bone metastases.

A panel of bone turn-over markers was assessed in 75 normocalcemic patients bearing bone metastases from breast cancer (BC), and in 25 advanced/metastatic BC patients without clinical appearance of bone involvement. 115 healthy women, stratified in three subgroups according to age served as controls. Bone formation was investigated by measuring serum carboxyterminal propeptide of type I procollagen (PICP), Bone Gla Protein (BGP, osteocalcin), bone isoenzyme of alkaline phosphatase (BALP); bone resorption by measuring serum carboxyterminal telopeptide of type I collagen (ICTP), fasting urinary hydroxyproline/creatinine (OHPro/Cr) and calcium/creatinine (Ca/Cr). In patients with bone metastases the percent of supranormal values (higher than mean plus 2 SD of the age-matched controls) ranged between 25% and 40% for indices of bone formation, about 73% for both ICTP and OHPro/Cr and about 30% for Ca/Cr. The median levels of all bone turn-over markers were higher in bone metastatic patients than in those without apparent skeletal involvement, but significance was attained only for OHPro/Cr, Ca/Cr and BALP. Supranormal levels of ICTP and OHPro/Cr were also found in about 65-70% of patients without apparent skeletal involvement. ICTP and Ca/Cr significantly correlated with bone pain score, BALP, ICTP, Ca/Cr significantly correlated with the number of tumour appearances in bone. In conclusion, the bone resorption indices, ICTP and OHPro/Cr, are much more frequently elevated than bone formation indices in BC patients with or without skeletal involvement. Their potential use in the early detection of bone metastases is hampered by the insufficient knowledge on specificity. Among the biochemical markers evaluated, Ca/Cr, ICTP and BALP, due to correlation with clinical aspects, appear the most interesting for follow-up studies.

Serum levels of carboxyterminal propeptide of type I procollagen in cancer patients with osteoblastic and osteolytic bone metastases.

Serial monitoring of serum and urinary markers of bone regeneration may provide an indirect assessment of the activity of bone metastases. We measured serum levels of carboxyterminal propeptide of type I procollagen (PICP), a new marker of bone formation, in 236 control subjects, stratified according to age and sex, and in 122 cancer patients: 80 with breast cancer (BC) (42 with osteolytic bone metastases) and 42 with prostate cancer (PC) (31 with osteoblastic bone metastases). An inverse correlation between age and serum PICP levels was found in healthy men (r = -0.30), but not in women, PICP levels were significantly higher in patients with osteoblastic metastases compared to age-matched control subjects and patients with advanced disease not involving the skeleton. The sensitivity of PICP was 64% for detecting osteoblastic metastases, and 12% for detecting osteolytic metastases. Serum PICP determination may have a diagnostic role for osteoblastic activity.

Metabolic effects of single-dose pamidronate administration in prostate cancer patients with bone metastases.

BACKGROUND: Increased osteolysis usually accompanies sclerotic bone metastases from prostate cancer. This provides a rationale for the use of bisphosphonates to treat bone pain and prevent skeletal complications. METHODS: The fasting urinary levels of calcium, hydroxyproline (OHPRO), pyridinolines (PYD), deoxypyridinolines (DPYD), collagen cross-linked N-telopeptide (NTX) and the serum values of calcium, total alkaline phosphatase and relevant bone isoenzyme, bone gla protein (BGP), carboxy-telopeptide of type I collagen (ICTP) and parathyroid hormone (PTH) were determined at baseline and on the 15th, 30th, 60th and 90th days after single-dose (90 mg) pamidronate administration in 35 consecutive prostate cancer patients with bone metastases. These biochemical indices and serum interleukin 6 (IL-6) were also measured after four days in the last consecutive 17 cases. RESULTS: PYD, DPYD and NTX showed a significant decrease lasting four weeks (p<0.01, <0.01 and <0.001, respectively). OHPRO and ICTP did not change significantly. The NTX decline was greater than that of PYD and DPYD (maximum percent decrease: -71.3, -23.1 and -28.2, respectively). Bone formation markers and serum calcium did not change significantly. Serum PTH showed a rapid initial increase followed by a slow decrease (p<0.001). DPYD and NTX patterns did not correlate with changes in bone pain. As observed in the last 17 cases, the maximum osteolysis inhibition after pamidronate occurred on the fourth day after drug infusion. Serum IL-6 levels showed a short-lived decrease preceded by a transient rise on the fourth day. CONCLUSIONS: Pamidronate is able to induce a decrease in bone resorption without significantly influencing bone formation. The maximum decrease in bone resorption occurs very early. NTX is the most sensitive bone resorption marker in bisphosphonate therapy monitoring. Changes in IL-6 but not bone resorption markers may be useful in the prediction of symptomatic response.

Shifted distribution of cation-related cyst types in post-menopausal patients with gross cystic disease of the breast.

Gross cystic disease of the breast (GCD) is rarely seen after the menopause. Recent work has shown that by measuring electrolytes in the breast cyst fluid (BCF) it is possible to identify two principal classes of cyst, designated Type 1 (K+/Na+ greater than 1.5) and Type 2 (K+/Na+ less than 0.66). A smaller, intermediate class (Type 3) also appears to exist. We measured K+, Na+ and dehydroepiandrosterone sulphate (DHA-S) in 38 BCF samples aspirated from 33 women with GCD who had undergone spontaneous menopause at least 1 yr previously. Statistically significant correlations were found between DHA-S and cations (positive in relation to K+, P less than 0.001; negative in relation to Na+, P less than 0.001). The distribution of cyst types was shifted with respect to that characteristic of cases that occur at an earlier age: whereas Type 1 cysts predominate in menstruating women, Type 2 cysts proved more numerous in the post-menopausal subjects. The difference was statistically validated (P less than 0.001). The results seem to indicate a sharp reduction in high K+, high DHA-S cysts after the menopause, which may be paralleled by a decrease in the associated apocrine metaplasia. In view of the major biochemical differences between Type 1 and Type 2 cysts and of the suggested differences as regards cancer risk, classification of post-menopausal patients with GCD by cyst type is critical prior to any clinical trial or follow-up.

Circadian profile of serum melatonin in Cushing's disease and acromegaly.

We evaluated the circadian profiles of serum melatonin (MT) and cortisol in 6 patients with Cushing's disease while those of serum MT and GH were evaluated in 8 patients with acromegaly. The control group consisted of 15 healthy subjects in whom MT, cortisol and GH were determined. The presence of a circadian rhythmicity was validated by the cosinor method, while the diurnal and nocturnal amount of MT secretion were expressed in terms of area under the curve. Gross alterations of MT rhythm were not apparent in Cushing's patients. In acromegalics, we observed a blunted day-night oscillation of MT accounted for by a significant increase of its secretion during the day-time period.

Cohort study of association of risk of breast cancer with cyst type in women with gross cystic disease of the breast.

OBJECTIVE: To assess correlation between type of breast cyst and risk of breast cancer in women with gross cystic disease of the breast. DESIGN: Cohort study of women with breast cysts aspirated between 1983 and 1993 who were followed up until December 1994 for occurrence of breast cancer. SETTING: Major cancer prevention centre. SUBJECTS: 802 women with aspirated breast cysts. MAIN OUTCOME MEASURES: Type of breast cyst based on cationic content of cyst fluid: type I (potassium:sodium ratio > 1.5), type II (potassium:sodium ratio < 1.5), or mixed (both types). Subsequent occurrence and type of breast cancer. RESULTS: After median follow up of six years (range 2-12 years) 15 cases of invasive breast cancer and two ductal carcinomas in situ were diagnosed in the cohort: 12 invasive cancers (and two carcinomas in situ) among the 417 women with type I cysts, two cancers among the 325 women with type II cysts, and one among the 60 women with mixed cysts. The incidence of breast cancer in women with type I cysts was significantly higher than that in women with type II cysts (relative risk 4.62 (95% confidence interval 1.26 to 29.7)). These results were confirmed after adjustment for several risk factors for breast cancer (relative risk 4.24 (1.12 to 27.5)). CONCLUSIONS: The increased risk of breast cancer of women with breast cysts seems to be concentrated among women with type I breast cysts.

[Reduction of periodontoid masses following posterior arthrodesis: review of two new cases not linked to rheumatoid arthritis]. / Reducción de las masas periodontoideas tras artrodesis posterior: revisión a propósito de 2 casos no vinculados a artritis reumatoide.

Inflamatory periodontoid pannus is quite common in patients with rheumatoid arthritis. However, the occurrence of a pannus-like periodontoid mass that is unassociated with rheumatic inflammation is less frequent. Transoral surgery associated with a posterior stabilization has long been considered one of the most efficient methods to resolve the problem of instability in patients presenting neurological deficits secondary to the pannus. We present two cases of non rheumatic etiology, in which an occipito-cervical arthrodesis was used to resolve the proliferative lesion around the odontoid apophysis. Two women (67 and 60 years old respectively) presented symptoms of pain and neurological deterioration with an antecedent of possible past odontoid fracture in one case, and a previous large anterior cervical arthrodesis to correct spondylarthrosis in the other case. Both patient's neurological condition improved after placement of an arthrodesis through a posterior approach.