Transnasal sphenopalatine ganglion blockade for acute facial pain: a prospective randomized case-control study.

OBJECTIVE: Long-term physical inactivity can cause the atrophy of skeletal muscle. The aim of this study is to explore the underlying mechanisms of physical inactivity-induced atrophy of skeletal muscle. MATERIALS AND METHODS: 14 Sprague- Dawley (SD) male rats were divided into 2 groups including normal control (NC) and hindlimb suspension (HS) groups. After two weeks of HS stimulation, the ratio between skeletal muscle weight and body weight, and cross-sectional area (CSA) of skeletal muscle fibers, were measured. Western blot was applied to evaluate the expression of proteins associated with atrophy and autophagy. The transmission electron microscope was used to observe the ultra-microstructure and the mitochondrial quality of skeletal muscle. RESULTS: The rats subjected to 2-week HS treatment presented an evident atrophy of the skeletal muscle with a significantly reduced ratio between skeletal muscle weight and body weight, and smaller cross-sectional area (CSA) of skeletal muscle fibers when compared with control rats. Meanwhile, HS stimulation resulted in the damage of mitochondria, the increased expression of MuRF1 and Atrogin-1/MAFbx, and enhanced apoptosis, as well as dysfunctional autophagy in skeletal muscle. CONCLUSIONS: HS-induced skeletal muscle atrophy involves the activation of AMPK/FoxO3 signal pathway, evidenced as AMPK phosphorylation, FoxO3 activation, and Atrogin-1 and MuRF1 up-regulation. FoxO3-mediated autophagy plays an important regulatory role in HS-induced skeletal muscle atrophy.

Image-guided fine-needle aspiration cytology and flow cytometry phenotyping of neck lymphadenopathy for the diagnosis of recurrent lymphoma.

OBJECTIVE: In patients with a history of lymphoma, each lymphadenopathy should be carefully evaluated. The aims of this study were to evaluate (i) the usefulness of high-resolution ultrasonography (US), US-guided fine-needle aspiration cytology (FNAC) and flow cytometry phenotyping (FCP) together in the diagnosis of recurrent lymphoma and (ii) whether these tools were independent predictors of correct results. DESIGN: Retrospective cohort study with stepwise forward logistic regression analysis of results. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 151 patients with a history of lymphoma who developed a cervical mass during follow-up. METHODS: On neck US, a lymphadenopathy was shown in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided FNAC combined with FCP were immediately performed. All patients had surgical excision and subsequent histological examination of the enlarged node(s), to establish lymphoma subclassification. RESULTS: Final histology confirmed recurrence in 82 (63.6%) patients. According to the logistic regression analysis, FNAC and FCP were independent predictors of correct results (P = 0.009 and 0.028, respectively) and did not interfere with each other. The sensitivity, specificity and accuracy of the combination of all of the tools were 98.8%, 100% and 99.2%, respectively, and the area under the receiver operating characteristic curve was 0.902 (95% CI: 0.797-0.986). CONCLUSION: This minimally invasive procedure is easily performed and should be recommended for all patients with cervical lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or surgical excision if recurrence was excluded.

Ultrasonic dissection system technology in breast cancer: a case-control study in a large cohort of patients requiring axillary dissection.

In the sentinel node era, axillary dissection (ALND) for breast cancer (BC) is required much less frequently than in the past. However, complications, such as prolonged drainage output and seroma formation, are still observed. Harmonic dissection devices (HDDs) are widely used in laparoscopic and minimally invasive surgery to reduce collateral damage during tissue dissection, but its usefulness in breast surgery is unclear. The aim of this study was to evaluate the efficacy of HDDs compared to that of conventional dissection in performing ALND. One hundred thirty-nine women (median age 61 years, range 34-71 years) with confirmed pT1-2 primary infiltrating ductal BC undergoing curative surgery were enrolled in the study. The population was prospectively randomized between two age- and stage-matched arms: group A (cases)-68 (48.9 %) patients (HDD technique), versus group B (controls)-71 (51.1 %) patients (conventional technique). In group B, skin flaps were obtained using a scalpel, scissors, and electrocautery which was never used for ALND. In group A, for each operation time, the HDDs were used exclusively. The mean operative time, intraoperative blood loss, and drainage output were (A vs. B) 95 ± 22 versus 109 ± 25 min, 56 ± 12 versus 86 ± 15 mL, and 412 ± 83 versus 456 ± 69 mL, respectively (p < 0.01). Twenty-nine (20.9 %) patients developed an axillary seroma: 9 (13.2 %) and 20 (28.2 %) for groups A and B, respectively (p = 0.030). Our study confirms that in patients with BC requiring ALND the use of HDDs is more time efficient than conventional surgery, and reduces intraoperative bleeding, the amount of drainage, and the risk of seroma formation. These results may lead to several short- and long-term advantages. Thus, a careful evaluation of the cost-benefits of nontraditional tools, such as HDDs, should be performed in all patients undergoing modified radical or partial mastectomy and ALND for BC.

Treatment of estrogen receptor-positive breast cancer.

Estrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately 70% of human breast cancers (BCs) are hormone-dependent and ER-positive. The introduction of adjuvant systemic therapy led to a significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with ER+ tumors, who may receive ET alone or in combination with cytotoxic therapy. Adjuvant ET currently consists of (i) ovarian suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs). In patients with ER+ tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective than adjuvant chemotherapy alone. Tamoxifen is the best established SERM, has favorable effects on BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For these reasons, other SERMs have been developed. Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus. The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs. In postmenopausal patients with ER+ BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront therapy. Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging.

Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas.

Sarcomas of the soft tissue are a heterogeneous, rare and complex group of mesenchymal malignant tumors, accounting for less than 1% of all adult malignancies and about 10-15% of childhood cancer. Despite local disease control obtained with surgery and pre- or postoperative radiotherapy, roughly one half of patients with high-grade tumors experience metastatic disease. The adjunction of chemotherapy, either before or after resection, is not currently viewed as standard practice due to the lack of reproducible impact on survival. The 1997 SMAC meta-analysis based on individual data from randomized studies confirmed a significant impact of adjuvant chemotherapy on both local and metastatic relapse, without any significant benefit on survival. Further meta-analyses demonstrated a significant benefit also in overall survival. Yet, the latest adjuvant EORTC trial was disappointedly negative. To date, adjuvant chemotherapy may be recommended as a reasonable option for the high-risk individual patient who should be well informed on the possible risks and benefits of treatment. Also the indications for neoadjuvant chemotherapy remain controversial. A local benefit may be gained, facilitating surgery, but data on survival are limited and affected by a strong patient selection bias. In order to improve our knowledge on sarcomas and to offer patients the best of current standards, we strongly recommend that all patients be referred to a sarcoma multidisciplinary group, under whose supervision they could receive the correct combined-modality management as well as have access to new clinical trials appropriately stratified for risk and histological and/or molecular subtypes.

Targeted approaches to triple-negative breast cancer: current practice and future directions.

Triple-negative breast cancer (TNBC), that is breast cancer which stains negatively at immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2), comprises a particularly aggressive subtype of breast cancer, with high rate of early local and distant relapse. TNBC have demonstrated sensitivity to cytotoxic treatment regimens, but in the absence of HER2, ER and PR there is no benefit from hormonal therapy or trastuzumab. The lack of known specific molecular targets has promoted abundant research in order to find possible "vulnerabilities" in TNBC and the evaluation of novel biomarkers overcoming the traditional approach based on hormonal receptors and HER2-targeted therapy is one of the priorities in breast cancer research. Drugs under investigation can be broadly subdivided into four groups: (1) Agents that create DNA damage (i.e. cisplatin, cyclophosphamide); (2) Agents that inhibit poly (ADP-ribose) polymerase (PARP); (3) Tyrosin-kinase inhibitors and monoclonal antibodies; (4) Agents that inhibit downstream signals. Several preclinical and early phase clinical trials for the treatment or management of patients with triple-negative breast tumors are underway. Nonetheless, so far the major issue to deal with when trying to provide evidence for TNBC is the small numbers of the sample in the clinical studies and the retrospective nature of most of them. Future large studies could help in defining optimal treatment strategies for TNBC, both in the advanced setting as well as in the (neo) adjuvant setting.

Calcium metabolism & hypercalcemia in adults.

Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolic pathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, and renal handling, but hypercalcemia occurs when at least 2 of these 3 metabolic pathways are altered. Calcium metabolism mainly depends on the activity of parathyroid hormone (PTH). Its secretion is strictly controlled by the ionized serum calcium levels through a negative feed-back, which is achieved by the activation of calcium-sensing receptors (CaSRs) mainly expressed on the surface of the parathyroid cells. The PTH receptor in bone and kidney is now referred as PTHR1. The balance of PTH, calcitonin, and vitamin D has long been considered the main regulator of calcium metabolism, but the function of other actors, such as fibroblast growth factor-23 (FGF-23), Klotho, and TPRV5 should be considered. Primary hyperparathyroidism and malignancy are the most common causes of hypercalcemia, accounting for more than 90% of cases. Uncontrolled hypercalcemia may cause renal impairment, both temporary (alteration of renal tubular function) and progressive (relapsing nephrolithiasis), leading to a progressive loss of renal function, as well as severe bone diseases, and heart damages. Advances in the understanding of all actors of calcium homeostasis will be crucial, having several practical consequences in the treatment and prevention of hypercalcemia. This would allow to move from a support therapy, sometimes ineffective, to a specific and addressed therapy, especially in patients with chronic hypercalcemic conditions unsuitable for surgery.

Imaging studies in hypercalcemia.

Hypercalcemia is a relatively common clinical problem, mainly (>90%) related to primary hyperparathyroidism (HPT) and malignancies. The anatomical and functional imaging techniques available for locating enlarged parathyroid glands include ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine imaging techniques. The most commonly employed are US and parathyroid scintigraphy, while CT, MRI, positron emission tomography (PET)/CT, and selective venous sampling are generally used in patients with persistent or recurrent HPT, or when findings of non-invasive studies are negative or conflicting. The reported accuracy is 57-93%, 54-93%, and up to 95% for US, (99m)Tc-sestamibi scintigraphy, and the two modalities combined, respectively. A multimodality approach (x-ray, whole-body scintigraphy, CT, MRI, and PET) is usually recommended for whole body assessment in cases of cancer-induced hypercalcemia (CIH). Imaging studies should evaluate each organ (i.e. breast, kidney, prostate, parathyroid) potentially involved in the pathogenesis of hypercalcemia in patients with CIH. In cases of skeletal metastases, when findings on plain x-ray or bone scans are uncertain, any unexplained region of abnormal uptake should be examined by MRI and/or ¹8F-fluoro-2- deoxyglucose (FDG)-PET/CT, which has proved more accurate than classical bone scintigraphy, especially for dealing with hematologic malignancies. A number of radionuclide tracers, other than ¹8F-FDG, are available for use in selected cases to locate specific tumors (i.e. 68Ga for neuroendocrine tumors). This is a review of recently published information on the imaging techniques currently available for patients with hypercalcemia.

Malignant hypercalcemia.

Malignancy-associated hypercalcemia (MAH) is one of the clinical emergencies in medical oncology, arising early or, more often, during the late phases of disease. Prevalence cannot be estimated accurately because previous figures of 5-30% of all cancer patients have progressively reduced thanks to the widespread use of bisphosphonates for the prevention of skeletal events. The classic distinction of humoral vs. osteolytic hypercalcemia is still relevant from an etiological point of view, but should not be considered as a rigid alternative since both mechanisms may be active in the same patients and the activation of the RANKL pathway is a common pathogenetic mechanism. Parathyroid hormone-related protein mimics the effects of PTH on the bone and kidney (tubular calcium resorption) and may represent an attractive druggable target, but additional agents (cytokines or other mediators) as well as ectopic production of 1,25(OH)2D3 may give an important contribution to humoral hypercalcemia. Conversely, bone invasion by cancer cells determines massive bone reabsorption due to the release of proteolytic enzymes and pro-osteolytic agents with paracrine activity on adjacent bone and stromal cells. When cancer patients develop headache, confusion, de-hydration and tremors hypercalcemia should be suspected although slow rise of calcium levels may produce more indolent symptoms. Bisphosphonates (with or without hydration and diuretics) may efficiently control MAH but only if an active treatment for the underlying cancer is promptly started. The anti-RANKL monoclonal antibody denosumab represents a novel agent able to revert the vicious cycle of bone metastases and data from phase III studies are currently showing promising activity in reverting bone resorption with manageable toxicity.

Endocrine therapy of breast cancer.

Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause-like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer.

Relationship between body mass index, age and hypoxemia in patients with extremely severe obesity undergoing bariatric surgery.

BACKGROUND: Morbid obesity is frequently accompanied by serious co-morbidity, enclosed obstructive sleep apnea and hypoventilation syndrome, and thus many morbidly obese patients require surgical interventions. The aim of this study was to evaluate the relationship between arterial oxygen (pO2) and carbon dioxide (pCO2) partial pressure, age, loss of excess weight, and body mass index (BMI) in obese patients scheduled to undergo bariatric surgery. PATIENTS AND METHODS: A group of 11 patients (4 men, 7 women, median age 38 years, range 23-58 years) with extremely severe obesity (BMI>50 kg/m²) underwent laparoscopic Roux-en-Y gastric bypass. Preoperatively, BMI, pO2, and pCO2 were 52.7±2.4 kg/m², and 70.9±5.3 and 43.1±6.5 mmHg, respectively. Hypoxemia (pO2<75 mmHg) was present in all patients, but no relationship between BMI and age (R=-0.24, p=0.44) or between BMI and pO2 (R=0.09, p=0.77) was found. RESULTS: As expected, there was a significant correlation between age and both pO2 (R=-0.58, p=0.04) and pCO2 (R=0.85, p=0.0004), while no relationship between BMI and age (R=-0.24, p=0.44), nor between BMI and pO2 (R=0.09, p=0.77) was found. Finally, there was a significant correlation between pO2 and loss of excess weight (R=-0.69, p=0.02). No intra- or postoperative complications were observed, and 12 months after surgery BMI decreased to 32.5±2.7 kg/m² (p<0.001) and pCO2 to 37.9±5.3 mmHg (p=0.05), while pO2 reached 85.8±6.8 (p<0.001) mmHg. CONCLUSIONS: In obese patients, the severity of hypoxemia is mainly related to age. The amount of weight reduction, rather than lower baseline BMI values, may justify the significant postoperative pO2 improvement.

Medical Treatment of Hirsutism in Women

Hirsutism is the presence of excess hair growth in women in the typical male hair growth areas, thereby reflecting a deviation from the normal female hair pattern. It affects from 5% to 10% of women, depending on age, menopausal status and ethnic background. The presence of hirsutism is very distressing for women, and subsequently may have a negative impact on their psychosocial life. In the treatment of hirsutism several options are now available, including pharmacologic regimens and cosmetic measures. Both the hormonal profile of the patient and her expectations and preferences should guide the therapeutic approach. The aims of the medical therapy are suppression of excessive androgen production, inhibition of peripheral action of androgens, and treatment of patients at risk for metabolic disorders or reproductive cancers. For other diseases related to endocrine abnormalities, such as thyroid disorders or Cushing's syndrome, specific treatment is mandatory. After an ineffective local approach by direct hair removal, a pharmacological treatment should be suggested, using estrogen and progestin combinations, antiandrogens (i.e. cyproterone acetate, spironolactone) or both as a first line. Finasteride, gonadotropin-releasing hormone agonists, and glucocorticoids should be used in selected cases. Adequate contraception is also recommended if antiandrogens are used. Unfortunately, since systemic therapy reduces hair growth in less than 50% of cases, hirsute women frequently require cosmetic measures. The use of a logical combination of different options has been shown to achieve a satisfactory result in most cases. This review provides information and suggestions about the current options of treating hirsutism.

Medical treatment of malignancy-associated hypercalcemia.

Malignancy-associated hypercalcemia (MAH) is the commonest cause of hypercalcemia in hospitalized patients. Its incidence is 15 cases per 100,000 person-year. Such complication develops in almost 10% of patients with advanced cancer representing, ultimately, the most frequent cause of death in several patients with cancer. Parathyroid hormone related protein (PTHrP), which has strong homology to parathyroid hormone, is the commonest hormonal mediator of MAH. Overall, about 80% of patients with MAH have increased PTHrP serum levels. Bisphosphonates are synthetic analogues of pyrophosphate, and represent the principal support of treatment. Several bisphosphonates have shown to decrease serum calcium levels by inhibiting PTH-dependent osteoclast activation. They are potent and effective inhibitors of osteoclast-mediated bone resorption, and have shown antiangiogenic properties in some experimental models. At present, pamidronate, zoledronate and ibandronate should be considered the drugs of choice in the treatment of MAH. Old agents such as mithramycin, calcitonine, and gallium nitrate have practically been abandoned due to their limited activity and huge side effects, especially for the kidney. A new experimental approach to MAH involves the blockade of receptor activator of nuclear factor-kappa B ligand, usually abbreviated as RANKL. RANKL is a key element in the differentiation, function, and survival of osteoclasts, which plays an essential role in removing Ca(++) from the bone in response to PTH stimulation. This review provides information about the actual medical treatment of MAH.

Which benefit from adding gemcitabine to vinorelbine in elderly (>or=70 years) women with metastatic breast cancer? Early interruption of a phase II study.

BACKGROUND: Since vinorelbine and gemcitabine are both active in breast cancer with moderate toxicity, in 2002 we started a phase II trial with a combination regimen in elderly patients. PATIENTS AND METHODS: To evaluate complete plus partial response rates and toxicity of first-line vinorelbine 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 3 weeks, in women>or=70 years with advanced breast cancer and measurable lesions. All patients underwent multidimensional geriatric assessment before enrollment. A two-step design was applied, and the trial would be completed if an overall response rate>or=30% was obtained with a grade 3-grade 4 (G3-G4) toxicity rateor=70 years outside the setting of controlled clinical trials.

Accuracy of ultrasonography and 99mTc-sestamibi scintimammography for assessing axillary lymph node status in breast cancer patients. A prospective study.

AIMS: The aim of this study was to evaluate the sensitivity, specificity and accuracy of axillary ultrasonography (US) and (99m)Tc-sestamibi scintimammography (SSM) in patients with breast cancer (BC) undergoing curative surgery. METHODS: A series of 77 consecutive women (median age 54 years, range 36-70) with primary BC underwent both US and SSM from 2 to 15 (median 4) days prior to curative surgery. The results of imaging studies were compared against the final pathology. Breast-conserving surgery with axillary node (AN) dissection was performed in 49 (63.6%) patients, and modified radical mastectomy in 28 (36.4%) patients, according to the tumour staging. RESULTS: Final pathology showed 5 pT1bN0, 1 pT1bN1, 28 pT1cN0, 19 pT1cN1, 7 pT2N0, and 17 pT2N1 BC. Overall, 719 AN were removed of which 106 (14.7%) were metastatized nodes (median 3, range 1-5 per patient). The sensitivity, specificity and accuracy were 67.6%, 80.0%, and 74.0% for US, 78.4%, 85.0%, and 81.8% for SSM, and 91.9%, 92.5%, and 92.2% for US and SSM together, respectively. There was a significant difference (p<0.05) in the number of metastatized AN between patients with metastases correctly detected and undetected by both US (3.1+/-1.3 vs. 2.0+/-0.7) and SSM (3.2+/-1.3 vs. 1.7+/-0.7). CONCLUSIONS: Although the results of each diagnostic tests are strictly dependent on the number of the metastatized AN, the combination of axillary US and SSM is a sensitive low-cost procedure that should be suggested in all patients with BC, when a preoperative evaluation of the AN status is required.

A meta-iodobenzylguanidine scintigraphic scoring system increases accuracy in the diagnostic management of pheochromocytoma.

As observed by other authors, normal adrenal medullary tissue frequently gives an apparently positive meta-iodobenzylguanidine (MIBG) scan in cases studied using 123I-MIBG and less frequently 131I-MIBG. The aim of this study was to assess the usefulness of a scoring system, based on different uptakes of the radiopharmaceutical, to improve the accuracy of 123I-MIBG scintigraphy in patients with either adrenal or extra-adrenal pheochromocytomas. Charts from 67 consecutive patients (29 males and 38 females, median age 48 years, range 14-80 years) with suspected pheochromocytoma (either sporadic or familial: multiple endocrine neoplasia (MEN) 2a, MEN2b, Von Hippel-Lindau, neurofibromatosis type 1) who underwent 123I-MIBG scintigraphy (scans acquired 4-24 h after injection) from 1991 to 2004, were independently reviewed by two experienced nuclear medicine physicians using liver uptake as a reference (scores: 1, uptake absent or less than the liver; 2, equal to the liver; 3, moderately more intense than the liver; 4, markedly more intense than the liver). Interfering medications were discontinued for the appropriate time before MIBG injection. Histological data were obtained for all patients who underwent adrenalectomy. Scintigraphies were classified as positive using the following criteria: extra-adrenal focal uptake, adrenal enlargement together with non-homogeneous uptake and adrenal uptake more intense than the liver (score 3-4). After surgical resection, as confirmed by histological findings and long-term follow-up (range 1-14 years, average 9.25 years), 43 patients were considered true positives using the proposed scoring system, 20 were true negatives, four were false negatives and none was false positive. In conclusion, the proposed scoring system demonstrated high specificity (100%), sensitivity (91.5%) and accuracy (94%) in the management of pheochromocytoma. Positive predictive value and negative predictive value were 100% and 83.3% respectively. Normal adrenal tissue uptake was correctly discriminated from pheochromocytomas in 18 out of 20 patients, with adrenal uptake equal to the liver (grade 2), using the proposed cut-off level.

Biochemical markers of endothelial activation in primary hyperparathyroidism.

Patients with primary hyperparathyroidism (PHPT) have impaired vasodilation both dependent and independent of endothelium. The aims of our study were to measure three different biochemical markers of endothelial activation, i. e., plasma thrombomodulin, soluble(s) E-selectin, and von Willebrand factor, in PHPT patients before and one year after successful parathyroidectomy, and to distinguish the potential effect of hypercalcemia and/or high parathyroid hormone from that of major cardiovascular risk factors (diabetes mellitus, hyperlipidemia, hypertension, obesity, smoking habit) on endothelial function. Twenty consecutive patients with PHPT subdivided into two groups according to the absence (n = 8) or presence (n = 12) of one or more risk factors, and fifteen healthy normocalcemic subjects were studied. Baseline thrombomodulin levels were similar in the groups with and without risk factors, and in controls. In contrast, sE-selectin and von Willebrand factor were higher in PHPT patients with risk factors than in those without risk factors (p < 0.05 and p < 0.01, respectively) and controls (p < 0.01). Neither thrombomodulin nor sE-selectin changed after parathyroidectomy in either PHPT group. Plasma von Willebrand factor decreased (p < 0.01) in patients without risk factors, while persisting at high levels in patients with risk factors. In conclusion, in spite of a limitation due to the small number of patients, our study suggests that classic cardiovascular risk factors seem to be the main determinants for the high plasma levels of sE-selectin and vWF in PHPT. Together with unaltered thrombomodulin and sE-selectin levels, a plasma vWF decrease after parathyroidectomy might reflect a specific mechanism of its endothelial calcium- and/or PTH-stimulated secretion in some PHPT patients without risk factors. Whether a vWF reduction after parathyroidectomy may be used as a biochemical index for improved endothelial function in PHPT patients without risk factors has yet to be demonstrated in larger studies.

Relationship between prognostic factors of breast cancer and 99mTc-sestamibi uptake in patients who underwent scintimammography: Multivariate analysis of causes of false-negative results.

The complementary role of sestamibi scintimammography (SSM) in patients with breast cancer (BC) is well established. The aim of this study was to establish whether a relationship exists between sestamibi uptake, evaluated as a tumour-to-background ratio (TBR), and the main prognostic factors of BC. SSM with the measurement of TBR was performed preoperatively in 102 women (median age 57 years, range 32-81 years) who underwent curative surgery for primary BC. Final pathology showed 4 (3.9%) with pT1a, 17 (16.7%) with pT1b, 44 (43.1%) with pT1c and 37 (36.3%) with pT2 breast carcinomas. The overall sensitivity of SSM was 80.4%. An ANOVA showed significant (P<0.01) differences between the TBR of patients with G1 vs. G3 tumours, and between the TBR of those with G2 vs. G3 breast carcinomas. Moreover, there was a difference (P=0.021) between the TBR of patients (n=12, 11.8%) with CEA serum levels >10 ng/ml (2.031+/-0.420), and those with normal (n=90, 88.2%) CEA values (1.713+/-0.446), whilst no difference (P=NS) was found between patients (n=27, 26.5%) with CA 15-3 >30 U/ml (1.893+/-0.401) and those with normal (n=75, 73.5%) CA 15-3 values (1.699+/-0.462). There was a mild inverse correlation between TBR and both the oestrogen (R=0.25, P=0.011) and the progesterone receptor (R=0.23, P=0.02) rate. The logistic regression analysis showed that only size and CA 15-3 serum levels represent true independent parameters, but the function was able to predict only 11 out of 21 (52.4%) patients with false-negative SSM. TBR is independent of age and mainly correlates with the size of the tumour. There are no reliable preoperative prognostic factors that are really useful for improving SSM sensitivity in patients with small breast carcinomas.

Congenital anomalies of the spleen mimicking hematological disorders and solid tumors: a single-center experience of 2650 consecutive diagnostic laparoscopies.

Congenital anomalies of the spleen range from splenic lobulation, to accessory spleen to polysplenia. Though most of these anatomical variants have no clinical significance, an accessory spleen may simulate a tumor in the adrenal gland, pancreas, stomach or intestine. Alternatively, a missed accessory spleen may be the site of the relapse of a hematological disorder. We, therefore, assessed retrospectively: (i) the frequency of congenital anomalies of the spleen observed during 2650 consecutive laparoscopies and (ii) looked for possible misdiagnoses of the accessory spleen as hematological disorders or solid tumors located in the left upper quadrant of the abdomen. Congenital anomalies of the spleen were detected in 55 cases, accounting for 2.07%. Accessory spleens were observed in 44 patients (1.6%) and spleen lobulation in 11 (0.47%). An accessory spleen was the most common of the splenic anomalies. Among the 44 patients in whom an accessory spleen was discovered laparoscopically, the recognition of this anomaly prevented a relapse of a hematological disease in one case and avoided a useless exploratory laparotomy in the second, where the radiologist had interpreted this malformation as a space-occupying lesion. In the third case, the accessory spleen was initially misdiagnosed as a solid tumor of the pancreas, but was eventually recognized as a congenital anomaly by a second laparoscopy.