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We measured serum concentrations of bone Gla-protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150-450 micrograms/day for 6-33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2 +/- 4.2 micrograms/liter versus 8.0 +/- 3.3 micrograms/liter, P < 0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r = 0.67, P < 0.001). Also IGF-I concentrations were positively correlated with BGP (r = 0.66, P < 0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146 +/- 46 micrograms/liter versus 127 +/- 44 micrograms/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation. [ABSTRACT FROM AUTHOR]

Background and aims: It is well established that caloric restriction (CR) may influence metabolic and hormonal factors involved in cancer development and progression. Recently, several studies have demonstrated that CR may have a favorable impact on the response to systemic therapy in breast cancer (BC) patients. However, there is a lack of data regarding the influence of CR during neoadjuvant chemotherapy (NACT). Our study's primary aim was to evaluate CR's impact on BC patients undergoing NACT. Secondly, we investigated the nutritional efficacy and safety of this intervention. Methods : We performed a prospective, case-control study in two breast units. A diet group consisting of 39 patients undergoing NACT and CR was enrolled in our study at the same time. CR consisted of a 30% reduction in caloric intake, which increased to 50% on the days before, during, and after the administration of chemotherapy. A control group of 60 patients that underwent the same treatment approach only followed the general dietary recommendations for BC according to WCRF guidelines. The diet group was monitored during the study for both dietary adequacy and weight trends. Results: CR combined with NACT showed a statistically significant therapeutic response in tumor size (OR 2.94, IC 1.07-8.01, p = 0.009) and lymph node status (OR 3.22, IC 1.22-8.56, p = 0.001) compared to NACT alone, even after the adjustment for all biological parameters. Our data also showed the efficacy and safety of this intervention in both anthropometric and biochemical analyses. Conclusions: Patients who adhered to CR showed a better response to NACT, both in the breast and in the axillary lymph nodes, compared to the patients in the control group. Furthermore, the CR diet combined with NACT showed good tolerance and safety.

Background and Aims: Elderly subjects are characterized by a high prevalence of chronic obstructive pulmonary disease (COPD) and frailty. This study examined the predictive role of frailty on long-term mortality in elderly subjects with and without COPD., Methods: The study assessed mortality after a 12-year follow-up in 489 subjects with COPD and 799 subjects without COPD, selected in 1992. Frailty was assessed according to the Frailty Staging System scores ranging from 1 to 7., Results: After 12 years' follow-up, mortality was 48.1% in subjects without and 60.7% in subjects with COPD (p<0.001). With increasing frailty, mortality increased from 41.7% to 75.1% (p for trend <0.01) in subjects without and from 54.3% to 97.0% in subjects with COPD (p for trend <0.001). Multivariate analysis showed that both COPD [hazard ratio (HR)=1.34; 95% confidence interval (95% CI)=1.02-1.81; p=0.042] and frailty score (HR=1.69 for each unit of increase; 95% CI=1.42- 2.00; p<0.001) were predictive of long-term mortality. The frailty score also increased the risk of long-term mortality by 34% in the absence of COPD (HR=1.34 for each unit of increase; 95% CI=1.02-1.81; p<0.05) and by 80% in its presence (HR=1.80 for each unit of increase; 95% CI=1.28-2.53; p<0.001)., Conclusions: Long-term mortality was higher in elderly subjects with than in those without COPD. The clinical frailty score also significantly predicted mortality in subjects without and, even more, in those with COPD. Thus, clinical frailty may be considered a new prognostic factor to identify COPD subjects at high risk of mortality.

Ocular adnexal lymphoma is the most frequent malignancy occurring in the eye region. With regard to the histology of these lesions, 2% to 7% of non-Hodgkin's lymphomas located in the periocular region are mantle cell lymphomas. A few cases of mantle cell lymphoma characterized by a fairly indolent course and prolonged survival have been described in the medical literature. We here report on a patient with indolent mantle cell lymphoma presenting at relapse with an isolated eyelid mass that was treated with lens-sparing surface brachytherapy resulting in durable locoregional complete remission.

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.

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.

Assessment of the response of bone metastases to endocrine or chemotherapy is difficult, and true response rate is probably underestimated by UICC criteria. Biochemical markers of osteoblast activity, which is linked with bone healing, could be useful for early detection of treatment response. We studied changes in osteoblast function, assessed by serial serum total alkaline phosphatase (tALP) at 0, 1, 2, 3 months from the start of systemic therapy, in 31 patients bearing bone metastases from advanced breast cancer. After 1 month of endocrine or cytotoxic treatment, all responding patients (7/31) showed a significant rise in tALP (mean increase: 351 IU/l, p < 0.05) followed by a gradual decrease over the subsequent months (tALP flare). Transient increase in tALP was also found in 2/16 patients with stable disease who benefited from therapy. 2/8 patients with progressive disease showed a rise indistinguishable from responders, but the subsequent decrease was not apparent. These observations suggest that serum tALP profile is an earlier predictor of response than X-rays.