A proposed index of diffuse bone marrow [18F]-FDG uptake and PET skeletal patterns correlate with myeloma prognostic markers, plasma cell morphology, and response to therapy.

PURPOSE: The investigation of a semi-quantitative index in the pelvis to assess for diffuse bone marrow (BM) [18F]-FDG uptake and the investigation of PET skeletal patterns in multiple myeloma (MM) patients, in accordance with prognostic markers, clonal plasma cell (cPC) morphology, and response to therapy. METHODS: We prospectively analyzed [18F]-FDG PET/CT in 90 MM patients (newly diagnosed, 60; relapsed/refractory, 30). Among other PET/CT parameters, we calculated the ratio SUVmax pelvis/liver and examined for correlations with known MM prognostic parameters, cPC morphology (good vs. low/intermediate differentiation), and response to therapy. RESULTS: SUVmax pelvis/liver ratio was significantly lower for the group of good differentiation vs. intermediate/low differentiation cPCs (p < 0.001) and showed a positive correlation with BM infiltration rate, ß2 microglobulin, serum ferritin, international staging system (ISS), and revised ISS; no significant correlation was found with hemoglobin. A cutoff value of 1.1 showed an excellent specificity (99%) and high sensitivity (76%) for diffuse BM involvement (AUC 0.94; p < 0.001). Mixed pattern and appendicular involvement correlated with poor prognostic features while normal pattern, found in 30% of patients, correlated with good prognostic features. Presence of ≥ 10 focal lesions negatively predicted for overall response (p < 0.05; OR 4.8). The CT component improved the diagnostic performance of PET. CONCLUSION: This study showed, for the first time, that cPC morphology and markers related with MM biology, correlate with SUVmax pelvis/liver index, which could be used as a surrogate marker for BM assessment and disease prognosis; PET patterns correlate with MM prognostic features and response rates.

Blood pressure variability within a single visit and all-cause mortality.

BACKGROUND: Within-visit variability of repeated sequential readings of blood pressure (BP) is an important phenomenon that may affect precision of BP measurement and thus decision making concerning BP-related risk and hypertension management. However, limited data exist concerning predictive ability of within-visit BP variability for clinical outcomes. Therefore, we aimed to investigate the association between the variability of three repeated office BP measurements and the risk of all-cause mortality, independent of BP levels. METHODS: Data collected through the National Health and Nutrition Examination Survey (NHANES) were analysed. NHANES is a program of studies designed to assess health and nutritional status of adults and children in the United States. A complete set of three sequential BP measurements, together with survival status, were available for 24969 individuals (age 46.8±;19.3 years, 49% males). Multivariable logistic regression models were used to determine the prognostic ability of the examined demographic, clinical, and haemodynamic indices. RESULTS: Among various examined indices of variability of systolic (SBP) and diastolic (DBP) blood pressure measurements, the standard deviation of DBP (DBPSD) was the stronger independent predictor of mortality (odds ratio 1.064, 95% Confidence Interval: 1.011-1.12) after adjustment for age, sex, body mass index, smoking, SBP, heart rate, history of hypertension, diabetes mellitus, hypercholesterolaemia, and cardiovascular events. CONCLUSION: Within-visit variability of three sequential office DBP readings may allow for the identification of high-risk patients better than mean SBP and DBP levels. The predictive value of within-visit BP variability and methods to improve its clinical application are worthy of further research.

Primary angiosarcoma of bone. A case report.

BACKGROUND: Primary malignant vascular tumors of bone are very rare accounting for less than 1% of primary bone malignancies. They are characterized by unknown etiology, variable biologic behavior and histological appearance. Angiosarcoma is an aggressive malignant vascular tumor derived from mesenchymal cells with endothelial differentiation. CASE REPORT: We present a rare case of angiosarcoma of bone in a 47-year-old male operated for a lumbar disk herniation. During his transportation from the operation theater, a pathological intertrochanteric fracture of the right hip occured. The magnetic resonance imaging (MRI) revealed a bone lytic lesion located into the great trochanter of the right femur. Open surgical biopsy of the lesion was performed and the histological examination showed primary angiosarcoma of bone. The treatment included radiotherapy (300 cGy per fraction in 13 days) followed by excision of the proximal femur and custom made total hip arthroplasty. The diagnosis was confirmed on the surgical specimen.

Primary ovarian small cell carcinoma of pulmonary type with enlarged paraaortic lymph node masses: a case report and review of the literature.

INTRODUCTION: Small cell carcinoma of the ovary of pulmonary type, is a rare, aggressive tumour with poor prognosis and its optimal management is unclear. CASE PRESENTATION: A 55-year-old Caucasian woman presented with abdominal discomfort and left lumbar pain within a three-week period. At exploratory laparotomy, a 8 cm solid cystic mass of the left ovary was found infiltrating the sigmoid colon, and a bulky mass (11 x 7 x 4 cm) in the left paraaortic infrarenal region. Histopathological features resembling small cell carcinoma of the lungs and positive immunohistochemical stains provided a definite diagnosis of IIIC ovarian small cell carcinoma of pulmonary type. After six cycles chemotherapy with carboplatin and etoposide, the patient is still alive at 21 months from initial diagnosis. DISCUSSION: In this case, the absence of peritoneal involvement and the extensive paraaortic adenopathy is suggestive of a different pattern of spread of this rare tumour. Optimal treatment seems to be radical primary debulking surgery resulting in no residual disease, maximizing the effect of adjuvant chemotherapy for this biological aggressive tumour.

Oral Mucositis: understanding the pathology and management.

Oral Mucositis is a common complication of cancer therapy which may limit the completion of treatment and affect the quality of life of the patient. As we have come to understand its pathogenesis new developments in its management and prevention have allowed us minimize this side effect.

A rare case of renal cell carcinoma metastasizing to the uterine cervix.

Metastatic tumors to the uterine cervix originating from malignancies in other organs are very rare. A case of a 45-year-old white woman presenting with vaginal bleeding, due to renal cell carcinoma metastasizing to the cervix, is reported. The patient had been treated four years and five months earlier due to two primary malignancies: colon adenocarcinoma and renal cell carcinoma. After D&C, microscopic examination and immunohistochemical staining showed that the tumor was metastatic, originating from the renal cell carcinoma. Radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node resection followed, and postoperatively the patient received targeted therapy with sutinib malate. The possibility of metastasis from another primary should be considered in the differential diagnosis of tumors of the uterine cervix in order to plan optimal management.

Mammary tumor phenotypes in wild-type aging female FVB/N mice with pituitary prolactinomas.

Prolactin-secreting pituitary adenomas are common spontaneous lesions in aging FVB females. Prolactin-secreting pituitary proliferations play a significant role in mouse mammary tumorigenesis generally producing adenosquamous carcinomas. Since genetically engineered FVB mice are frequently used to study mammary tumor biology, we have examined a cohort of 64 aging wild-type FVB/N females to establish the prevalence and the nature of spontaneous mammary and pituitary tumors. Tissues from mammary and pituitary glands were studied by histopathology and immunohistochemistry. Of the 64 examined mice, 20 had pituitary tumors and 20 had mammary tumors. Mammary and pituitary tumors were associated in 17 mice. All pituitary tumors were prolactin-positive by immunohistochemistry and classified as prolactinomas. Fourteen mammary tumors, including 12 cases with and 2 without concurrent prolactinomas, were adenocarcinomas with different combinations of epithelial growth patterns. Five mice with prolactinomas had mammary tumors characterized by the epithelial-mesenchymal transition (EMT) phenotype. Estrogen receptor alpha (ERalpha)-positivity was observed for 14 of the 18 mammary tumors tested, including both adenocarcinomas with nuclear immunoreactivity and EMT-phenotype tumors with both nuclear and cytoplasmic immunoreactivity. No immunoreactivity for the progesterone receptor was observed. This study confirms that spontaneous prolactinomas and mammary tumors are both common and significantly associated lesions in FVB mice. Parity and age represented risk factors for the development of these tumors. Compared with previous reports, prolactinoma-associated mammary tumors displayed a broader morphologic spectrum, including cases with the EMT phenotype. The elevated number of prolactinoma-associated and ERalpha-positive mammary tumors opens intriguing possibilities concerning the role of ERalpha cytoplasmic localization during EMT tumorigenesis.

Clear cell ovarian carcinoma following polymyositis diagnosis: a case report and review of the literature.

BACKGROUND: The association of ovarian malignancy with dermatomyositis (DM) is well established from previous reports, while the relationship with polymyositis (PM) is rare. CASE REPORT: We report a case of a 50 years old nulliparous woman who developed clear cell ovarian cancer four years after the PM diagnosis. The patient presented with deep lower abdominal pain and distension. CA-125 was elevated and the preoperative MRI showed pelvic tumor occupying the Douglas pouch. Exploratory laparotomy revealed a gross mass of clear cell ovarian carcinoma. CONCLUSION: Physicians must be alert of the possibility of malignancy in patients with a previous diagnosis of polymyositis.

Immunohistochemical bcl-2 expression, p53 overexpression, PR and ER status in endometrial carcinoma and survival outcomes.

Immunohistochemical expression of bcl-2, p53, PR and ER in cases with endometrial carcinomas arrayed on a tissue microarray (TMA) was tested and correlated with clinicopathologic features, overall survival (OS), cancer-related survival (CRS) and disease-free survival (DFS). Seventy-seven patients with endometrial cancer were reviewed. Slides were evaluated by two pathologists blinded to patient clinical characteristics and survival data. Mean age of patients was 62.5 years (range 35-80), median follow up 60 months (range 9-120). Seventy-nine percent of patients were FIGO Stage I; 39% of the cases showed bcl-2 cytoplasmic staining and its expression was significantly correlated with low-grade tumor differentiation and age < or = 60 years. Nuclear p53 overexpression was detected in 23.4% of the cases and was significantly correlated with advanced stages (IIB-IV), non-endometrioid histology, nodal metastasis and advanced age (> 60 years). PR and ER were positive in 63.6% and 30% of the cases, respectively. Analysis of p53 overexpression and bcl-2 expression in relationship with PR and ER status showed a direct correlation between bcl-2 expression and PR positivity (p = 0.001). In a multivariate analysis FIGO staging was the only clinicopathologic parameter independently correlated with DFS. In conclusion p53 overexpression was directly associated with unfavorable clinicopathologic factors such as advanced stage, histologic subtype, advanced patient age and nodal metastasis. Bcl-2 expression was related with younger age, favorable grade and PR expression by tumor cells. Patient survival was not related to the tested biomarkers.

Alveolar soft-part sarcoma of the extremity: a case report.

Alveolar soft-part sarcoma (ASPS) is a rare form of soft tissue sarcoma and is most often seen in adolescents and young adults. Surgical excision of the primary tumor and pulmonary metastases has resulted in prolonged survival in some patients while the benefit of adjuvant chemotherapy and/or radiotherapy has been disputed. An 11- year-old boy with ASPS which presented with a markedly vascular tumor in the left thigh, and multiple bilateral pulmonary metastases 8 months after diagnosis is described. The patient has remained disease-free for over 5 years since the initial diagnosis.

Pelvic lymphadenectomy as alternative to postoperative radiotherapy in high risk early stage endometrial cancer.

OBJECTIVE: The purpose of the study is to evaluate whether surgery followed by radiotherapy in high-risk patients of early stage endometrial cancer can be replaced by formal surgical staging. Cancer-related survival and recurrence-free survival (RFS) were the endpoints of the analysis. STUDY DESIGN: One hundred and eighteen patients with endometrioid endometrial adenocarcinoma between 1996-2003 were reviewed. Patients with incomplete follow-up and extrauterine spread excluded, leaving 78 women in the final analysis. Low-risk patients (n=37) (Grade 1, myometrial infiltration <1/2 or Grade 2, <1/3), treated by standard surgical procedure including total abdominal hysterectomy, bilateral salpingo-oophorectomy and peritoneal washing, while staging lymphadenectomy (n=24) or postoperative irradiation (n=17) was added in the high-risk group (Grade 1, >1/2 or Grade 2, >1/3 or Grade 3). RESULTS: The median age of patients was 65 years (range, 35-80 years) and the median follow-up 38 months (range, 9-98 months). The recurrence rate in low-risk patients was 2.7%, the cancer-related survival 97.5% and RFS 97%, while in the high-risk patients 12%, 93% and 88%, respectively. Comparing the therapeutic modalities (staging lymphadenectomy vs. postoperative irradiation) in the high-risk group the cancer-related survival and RFS was not differed (P=0.70, P=0.90, respectively). The high grade of the tumor was significantly correlated with RFS, while age, stage and myometrial infiltration were not. No moderate or severe complications developed after lymphadenectomy, while two moderate gastrointestinal complications occurred after adjuvant radiotherapy. CONCLUSION: According our results the low-risk patients of early stage endometrial adenocarcinoma had excellent survival with minimal intervention. The cancer-related survival and RFS in high-risk patients concerning the therapeutic modalities were comparable. Poor tumor differentiation was the most unfavorable prognostic factor related with RFS. Moderate complications developed only after postoperative radiotherapy.

Results on the treatment of uterine cervix cancer: ten years experience.

The aim of the study is to present our experience in the treatment of uterine cervix cancer over the last decade. This is a retrospective study of 90 patients with cervical cancer treated in a University Department of Obstetrics and Gynecology from 1993 to 2002. After the disease was histologically confirmed and staged the patients were treated according to stage with surgery (S) radiotherapy (RT), RT alone or Chemoradiaton (C-RT). The course of the disease and follow-up was traced from patient notes and after a structured telephone questionnaire. Mean age of patients was 48 +/- 14.3 years (29-84). Nine of 90 patients (10%) were lost to follow-up. FIGO (1994) staging was I in 50% of patients, II in 33.5%, III in 13.5% and IV in 3%. The size of tumor was < or = 4 cm in 75%. Of the tumors 87% were of squamous histology and 13% adenocarcinomas. Patients were treated with cone biopsy (5.5%), type I hysterectomy pelvic RT (10%), radical (type II-III) hysterectomy and pelvic lymphadenectomy +/- radiotherapy (41%), RT alone in 38% and C-RT in 5.5%. Incidence of complications after surgery was 19.5% and after RT 12.5%. Mean follow-up was 41 +/- 19 months (6-110). Five-year survival in Stage I was 84%, Stage II 64% and Stage III 40%. A single patient with Stage IV disease is alive with disease after two years. In conclusion uterine cervical cancer has improved survival because of early diagnosis. Treatment should be individualized according to the status of disease. Surgery and RT had similar rates of complications.

Hydatid disease of the tarsal bones. A case report.

Hydatid disease is caused by the larval form of the tapeworm Echinococcus. Osseous cysts are rare and very few cases of foot infestation have been reported. We present the case of a 51-year-old woman who developed a palpable mass at the medial dorsal aspect of the right midfoot. Radiological examination showed cystic lesions in the cuneiforms and the navicular. The lesion was explored and several small cysts containing clear fluid were found. They were evacuated and the bone was curetted. The diagnosis of E. granulosus infestation was made histologically. After 15 years' follow-up there were no signs of recurrence. Osseous echinococcosis is a rare disease that may present as infective or neoplastic pathology. A high index of suspicion is necessary for its diagnosis, especially in patients who live in or travel to sheep-raising areas where hydatid disease is endemic.

Proprioceptive neuromuscular facilitation training induced alterations in muscle fibre type and cross sectional area.

OBJECTIVES: To compare the effects of proprioceptive neuromuscular facilitation (PNF) and isokinetic training on fibre type distribution and cross sectional area of the vastus lateralis muscle. METHODS: Twenty four male university students were divided into two equal groups: PNF training and isokinetic training (ISO). The training regimen for the PNF group consisted of three sets of 30 repetitions against maximal resistance, alternating two patterns of sequential movements of the right lower extremity: (a) toe flexion and ankle plantar flexion and eversion; (b) knee extension and hip extension, abduction, and internal rotation. The ISO group performed three sets of 30 repetitions alternating knee extension and flexion of the right leg at angular velocities of 180 and 90 degrees /s in an isokinetic dynamometer (Cybex). Both groups trained three times a week for a total of eight weeks. Muscle biopsy specimens were obtained from the right vastus lateralis muscle before and after training. RESULTS: The mean percentage area of type IIB fibre was significantly decreased (p<0.01) after eight weeks of PNF training, whereas that of type IIA fibre was significantly (p<0.05) increased. The mean percentage area of ISO trained type IIAB fibres exhibited an augmentative pattern (p<0.01) with a parallel reduction (p<0.05) in type IIA. Percentage fibre type distribution exhibited a similar pattern. CONCLUSIONS: Both PNF and ISO training alter fibre type distribution and mean cross sectional area. These changes occur in the type II fibre subgroup.

KIT expression in fetal, normal adult, and neoplastic renal tissues.

BACKGROUND: KIT is a transmembrane tyrosine kinase receptor, expressed in high amounts in various normal cells. In addition, c-kit mutation or activation is a major pathogenetic event in certain tumours (such as gastrointestinal stromal tumours). There are only limited data in the literature on the expression of KIT in normal and neoplastic renal tissues. AIMS: To investigate KIT expression in normal and neoplastic renal tissues. METHODS: KIT expression was evaluated by means of immunohistochemistry in paraffin wax embedded sections from 67 tissue samples. RESULTS: Eight of eight fetal kidneys, and 10 of 10 normal adult kidneys revealed cytoplasmic staining of renal tubules. The three cases of renal dysplasia studied expressed KIT in their normal and aberrant tubules. Two of 13 conventional renal cell carcinomas (RCCs), two of seven papillary type RCCs, four of seven chromophobe type RCCs, none of six nephroblastomas, seven of seven oncocytomas, two of two mesoblastic nephromas, and two of four angiomyolipomas were positive. CONCLUSION: KIT is expressed in normal fetal and adult renal tubules, and in a subset of renal tumours. The expression of KIT in these renal tumours may prove to have diagnostic relevance and/or therapeutic implications.

In vivo analysis of mammary and non-mammary tumorigenesis in MMTV-cyclin D1 transgenic mice deficient in p53.

Overexpression of the cyclin D1 oncogene and inactivation of the p53 tumor suppressor have both been implicated in substantial proportions of sporadic human breast cancers. Transgenic mice with cyclin D1 overexpression targeted to mammary tissue by the MMTV enhancer-promoter have been shown to develop mammary cancers. To investigate the relationship between pathways driven by cyclin D1 overexpression and p53 loss during the development of breast cancers, we crossed MMTV-cyclin D1 mice with p53 heterozygous null (p53+/-) mice. In such crossed mice, cyclin D1-driven mammary neoplasia would need to be substantially accelerated by p53 loss in order for mammary tumors to develop prior to the expected onset of non-mammary tumors characteristic of the p53-deficient background alone. Instead, in mice heterozygous or homozygous for p53 deficiency and simultaneously carrying the MMTV-cyclin D1 transgene, only tumors typically found in p53-deficient mice developed and mammary tumors were not observed. Interestingly, MMTV-cyclin D1/p53+/- mice appeared to develop these non-mammary tumors more rapidly than p53+/- mice, and a majority of the sampled non-mammary tumors from MMTV-cyclin D1/p53+/- mice showed 'ectopic' expression of the MMTV-driven cyclin D1 transgene. Within the constraints of possible genetic background effects and limited sensitivity due to the early emergence of non-mammary tumors, these observations provide no evidence that inactivation of p53 confers a major additional selective advantage to mammary cells overexpressing cyclin D1 in this animal model of human breast cancer. Interestingly, the results do raise the possibility that p53 inactivation might complement or cooperate with cyclin D1 deregulation during the development of some types of non-mammary tumors.

Does the term scaphocapitate syndrome need to be revised? A report of 6 cases.

This is a retrospective study of six patients with displaced fractures of the neck of the capitate. In four of the six patients the diagnosis was delayed by at least 1 week. After open reduction and internal fixation the results were assessed as excellent (three cases), fair (two cases) or poor (one case). In all cases there was a concomitant injury to the radial side of the wrist: in four cases this was a fracture of the waist of the scaphoid. In five of the six cases there was also an injury to the ulnar side of the wrist. As a scaphoid fracture does not always occur with the fracture of the neck of the capitate, we consider the term "scaphocapitate syndrome" inappropriate for this injury.

A solitary gastric Peutz-Jeghers type polyp: report of a case.

Peutz-Jeghers type polyps of the stomach are rare and almost always associated with intestinal polyposis and mucocutaneous pigmentation; a condition known as Peutz-Jeghers syndrome. The case presented in this report refers to a woman found to have a large solitary Peutz-Jeghers type polyp of the stomach, with a maximal diameter of 7cm. Extended investigation did not reveal intestinal polyposis or any other sign of Peutz-Jeghers syndrome. Because of the size of the polyp, a partial gastrectomy was performed. To the best of our knowledge, there are only three other reports in the literature of a solitary Peutz-Jeghers type gastric polyp occurring in the absence of Peutz-Jeghers syndrome. This patient is scheduled to undergo a follow-up examination every 2 years to detect any sign of the development of Peutz-Jeghers syndrome or malignancies commonly associated with it.

Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice.

The relationship between abnormal cell proliferation and aberrant control of hormonal secretion is a fundamental and poorly understood issue in endocrine cell neoplasia. Transgenic mice with parathyroid-targeted overexpression of the cyclin D1 oncogene, modeling a gene rearrangement found in human tumors, were created to determine whether a primary defect in this cell-cycle regulator can cause an abnormal relationship between serum calcium and parathyroid hormone response, as is typical of human primary hyperparathyroidism. We also sought to develop an animal model of hyperparathyroidism and to examine directly cyclin D1's role in parathyroid tumorigenesis. Parathyroid hormone gene regulatory region--cyclin D1 (PTH--cyclin D1) mice not only developed abnormal parathyroid cell proliferation, but also developed chronic biochemical hyperparathyroidism with characteristic abnormalities in bone and, notably, a shift in the relationship between serum calcium and PTH. Thus, this animal model of human primary hyperparathyroidism provides direct experimental evidence that overexpression of the cyclin D1 oncogene can drive excessive parathyroid cell proliferation and that this proliferative defect need not occur solely as a downstream consequence of a defect in parathyroid hormone secretory control by serum calcium, as had been hypothesized. Instead, primary deregulation of cell-growth pathways can cause both the hypercellularity and abnormal control of hormonal secretion that are almost inevitably linked together in this common disorder.

Prognostic implications of aberrations in p16/pRb pathway in urothelial bladder carcinomas: a multivariate analysis including p53 expression and proliferation markers.

OBJECTIVE: To assess the prognostic value of the expression of two negative regulators of the cell cycle, namely CDKN2/INK4a gene product (p16) and retinoblastoma gene product (pRb), in urinary bladder cancer in relation to clinicopathological parameters, proliferative fraction and p53 protein accumulation. METHODS: Paraffin sections from 139 patients with urothelial carcinomas were stained immunohistochemically with antibodies to p16 (F12), pRb (PMG3-245), p53 (DO1), PCNA (PC10) and Ki-67 (MIB-1). RESULTS: Diminished p16 and pRb expression occurred in 29 and 74% of cases, respectively, being associated with advanced stage but not with histological grade, papillary status or proliferation rate. In most cases (53%) with some fault in the p16/pRb pathway, only one gene was affected. A double-negative p16/pRb phenotype was comparatively uncommon (25%) and was usually seen in T3-T4 tumours. In survival analysis (either univariate or multivariate) aberrant p16 expression was an adverse prognostic parameter only in T3-T4 tumours. In contrast, the abnormal p16/pRb and p53/p16 phenotypes were linked to a diminished overall and disease-free survival (univariate analysis); p53/p16 abnormal expression was also found to be an independent predictor of reduced survival in muscle-invasive tumours, while proliferation markers were the only parameters with independent significance in superficial (Ta-T1) tumours. CONCLUSION: Our results suggest that lack of p16 immunoexpression, when combined with p53 accumulation, plays an important role in determining the clinical outcome in muscle-invasive urothelial carcinomas.