Somatostatin receptors over-expression in castration resistant prostate cancer detected by PET/CT: preliminary report of in six patients.

Prostate cancer (PC) is usually characterized by an excellent prognosis, largely due to little biological aggressiveness and the power of hormonal deprivation therapy. In spite of these favorable characteristics, however, a significant quota of patients does not respond to androgen deprivation therapy (ADT) and develop a progressive disease. Castration-resistant prostate cancer (CRPC) is defined by disease progression in spite of ADT. This progression may show any combination of a rise in serum prostate-specific antigen (PSA), clinical and radiological progression of pre-existing disease, and appearance of new metastases. This event is a striking change in the clinical scenario, since the power of treatment for CRPC patients with distant metastases is very limited. Somatostatin is a hormone produced by neuroendocrine cells. Its distant effects are mediated by the binding to five specific receptors, which are the most striking parameter for neuroendocrine. Various synthetic somatostatin agonists able to bind to the receptors have been synthesized during the past two decades for diagnostic and therapeutic purposes. Octreotide, the most popular of these, is widely used to treat patients affected by neuroendocrine tumors. A number of researches carried out in the past evaluated the possible neuroendocrine differentiation (NED) of PC cells in the castration resistant phase. If proved, the presence of a specific class of receptor on cell's surfaces should give a potentially biological target to be used for therapy. However, these studies led to contradictory results. Aim of our phase III diagnostic trial was to study "in vivo" the over-expression of somatostatin receptors (SSTRs) in CRPC patients by PET/CT after the administration of the somatostatin analog [(68)Ga-DOTANOC,1-Nal(3)]-octreotide labeled with (68)Ga. Every area of increased uptake corresponding to a metastasis detected with other methods was considered as SSTRs expressing. False positivity to SSTRs expression was considered those localizations with a suspicious uptake not confirmed by other radiologic procedures. On the other hand, metastatic lesions lacking the radiopharmaceutical's uptake were considered not SSTRs expressing metastases. The preliminary results in 6 of the 67 patients scheduled by our phase III trial showed metastases with a variable SSTRs expression in 2 patients.

Neuroendocrine Differentiation of Prostate Cancer Metastases Evidenced "in Vivo" by 68Ga-DOTANOC PET/CT: Two Cases.

Prostate cancer is the second most commonly diagnosed neoplasm in men. This neoplasm has usually excellent prognosis, mostly consequent to the early diagnosis and the effective hormonal therapy. However, significant percentages of patients treated with total androgen blockade therapy, escape to treatment and evolve toward a more aggressive type of cancer. This clinical entity, named castration-resistant prostate cancer, has few and less effective therapeutic opportunities. Therefore, any additional information concerning possible biological targets to therapy is welcome. Here we describe two cases in which 68Ga-DOTANOC PET/CT evidenced the somatostatin receptor overexpression by prostate metastases. The presence of these receptors may support with a more strong evidence the possibility to administer somatostatin analogs as an adjuvant therapy.

Final results of a phase 2A study for the treatment of metastatic neuroendocrine tumors with a fixed activity of 90Y-DOTA-D-Phe1-Tyr3 octreotide.

BACKGROUND: The objective of this study was to assess the efficacy of (90)Y-DOTA-D-Phe1-Tyr3 octreotide ((90)Y-DOTATOC) therapy with a fixed activity of 2.56 GigaBequerels bimonthly in patients with advanced stage, well differentiated neuroendocrine carcinomas. METHODS: In total, 38 patients were enrolled in this phase 2A protocol. All patients had gastroenteropancreatic neuroendocrine tumors in sharp clinical and radiologic progression despite previous surgery, chemotherapy, and biotherapy. Their survival rate after therapy with (90)Y-DOTATOC was compared with a chronologic control group of patients who had received biotherapy and chemotherapy and with results from a previous similar study. The progression-free survival rate after peptide receptor radionuclide therapy with (90)Y-DOTATOC was determined for all patients until they had documented disease progression according to Response Criteria in Solid Tumors, tumor-related death, or censoring. RESULTS: Seventeen patients (43.6%) had a partial response, 10 patients (25.6%) had stable disease, and 11 patients (28.2%) had progressive disease. A statistically significant difference was observed (P < .001) between the response to (90)Y-DOTATOC treatment and the response to biotherapy with somatostatin analogs and chemotherapy and also between the current results and the results from a previous similar study (P < .05). At the time of the current evaluation with ongoing follow-up for 30 patients, the median progression-free survival was 22.3 months. CONCLUSIONS: The results from this phase 2 study indicated that the treatment of metastatic neuroendocrine tumors with fixed (90)Y-DOTATOC activity is useful and safe.

Defunctioning stoma in high ASA grade, aged patients, with bowel occlusion due to advanced cancer: is it still worthwhile?

PURPOSE: The aim of this study was to assess the role of defunctioning stoma (DS) in elderly high-risk patients with bowel obstruction from advanced colorectal cancer, by exploring consistent variables of outcome, because every other procedure was unfeasible. MATERIALS AND METHODS: A 6-year survey in a single surgery unit (between 1999 and 2004) was retrospectively evaluated, allowing to collect a cohort of 75 patients, aged over 65, who overall presented such critical condition. Pre-operatively, American Society of Anaesthesiologist grade classification was used. Post-operative course was monitored by focusing on gauging symptom relief. So, a validated assessment scale was employed to evaluate physical distress symptoms, graduated on a Likert scale and compared at baseline and day 7, on days 7 and 30, post-operatively. Length of hospital stay (LHS), morbidity, in-hospital (within 30 days) and overall mortality (within 6 months) were also assessed. Paired t test was used as statistical analysis to ascertain improvement of symptoms. RESULTS: All symptoms improved significantly (range, p < 0.05 to p < 0.01) within the surveyed time, with exception of vomiting on day 30 (p = 0.14). Average LHS was 22.8 (standard deviation, +/-3.856) days. Overall morbidity was detected in 68 (91%) patients. In-hospital and overall mortality rates accounted for 27 (35.8%) patients and for 48 (100%) patients, respectively. CONCLUSIONS: The role of DS was effective to improve symptom relief but was poor in terms of morbidity and mortality control. So, ethical concerns have to be addressed, and medical treatment or stenting for left-side obstructions only should be considered as alternative procedures.

Rheumatological manifestations in diabetes mellitus.

Rheumatological manifestations of Diabetes Mellitus may be classified in: non articular, articular and bone conditions. Among non articular conditions, diabetic cheiroarthropathy, frequent in type I diabetes, the most important disorder related to limited joint mobility, results in stiff skin and joint contractures. Adhesive capsulitis of the shoulder, flexor tenosynovitis, and Duputryen's and Peyronie's diseases are also linked to limited joint mobility. Diffuse skeletal hyperostosis, due to calcification at entheses, is frequent and early, particularly in type 2 diabetes. Neuropathies cause some non articular conditions, mainly neuropathic arthritis, a destructive bone and joint condition more common in type I diabetes. Algodistrophy, shoulder-hand and entrapment syndromes are also frequent. Mononeuropathy causes diabetic amyotrophy, characterised by painless muscle weakness. Among muscle conditions, diabetic muscle infarction is a rare, sometimes severe, condition. Among articular conditions, osteoarthritis is frequent and early in diabetes, in which also chondrocalcinosis and gout occur. Rheumatoid arthritis (RA) and diabetes I have a common genetic background and the presence of diabetes gives to RA an unfavourable prognosis. Among bone conditions, osteopenia and osteoporosis may occur early in type 1 diabetes. Contrarily, in type 2 diabetes, bone mineral density is similar or, sometimes, higher than in non diabetic subjects, probably due to hyperinsulinemia.

Alignment and articular orientation of lower limbs: manual vs computer-aided measurements on digital radiograms.

PURPOSE: To compare the manual measurements of lower limbs on digital images with those obtained with dedicated software. MATERIALS AND METHODS: Forty patients with a clinical suspicion of lower limb deformity were enrolled. Eighty digital radiographs were produced with a remote-controlled radiography system (Philips Omnidiagnost). The measurements were taken separately by an Orthopaedic Surgeon and by a Radiologist, by hand and with the aid of software, respectively. Five parameters were assessed: femoral length, tibial length, distal-medial femoral angle, proximal-medial tibial angle and tibial-femoral angle. The statistical analysis of the comparison was based on Student's t-test. The inter-observer variability of the methods, manual and computer-aided, was evaluated with Fisher's F-test on a sample of measurements (20 lower limbs), taken by 5 different Orthopaedic Surgeons and Radiologists, respectively. RESULTS: There were no statistically significant differences between the measurements taken with the manual and computer-aided methods (p<0.05). The overall reproducibility of both methods was similar; conversely, the separate evaluation of angles and lengths showed that the computer-aided method was less variable in the measurement of angles and a little more variable in the measurement of lengths than the manual method. CONCLUSIONS: The computer-aided evaluation of the alignment and articular orientation parameters of lower limbs is as accurate and reliable as the traditional manual method, but is faster and allows better-quality images.