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Osteonecrosis of the Jaw (ONJ) related to drugs (bisphosphonates, denosumab, antiangiogenic and other agents) is an issue of care by the “Rete Oncologica di Piemonte e Valle d’Aosta” since 2005. The “Rete Oncologica” is a cancer network that include professionals (physicians, nurses, technicians, supporting staff, data managers, etc) of all the healthcare units that manage and treat patients with cancer and hematologic disorders in two regions (Piedmont and Aosta Valley, globally 4.4 million population) in the North-Western Italy. Besides study groups, research grants and organization of meetings, in order to facilitate the awareness of ONJ issues, on 2014 the network created specific ONJ-dedicated pages on the network website www.reteoncologica.it [http://www.reteoncologica.it] . In the area for healthcare staff , the reader can find an ONJ title, that opens to a ONJ front page (http://www.reteoncologica.it/area-operatori/osteonecrosi-dei-mascellari-onj) presenting links to recent issues (recommendations, meetings, papers, etc) and to an Archive with previous contents, classified for year (http://www.reteoncologica.it/area-operatori/osteonecrosi-dei-mascellari-onj/185-documenti-e-slide) . Preliminary altmetric evaluation of the ONJ pages (number of visits; median time of stay; etc) show a variable but steady access to the ONJ contents of the website, with occasional peaks.

Introduction: Chemotherapy-induced nausea, vomiting, and retching (CINVR) remains a common side effect of treatment. Most previous studies have focused on vomiting control; nausea and retching have been less explored. This study aimed at describing the incidence, severity, and impact on daily life (IDL) of CINVR in the acute (0–24 hours), delayed (>24–120 hours), and overall (0–120 hours) postchemotherapy periods and beyond 120 hours (until next chemotherapy administration); and the pharmacologic and nonpharmacologic strategies adopted by patients to relieve symptoms. Methods: This was a single-center, cross-sectional study of 60 patients undergoing chemotherapy. Participants reported the frequency, severity, and IDL of CINVR from the day of chemotherapy administration up to 120 hours thereafter and nausea and vomiting that occurred beyond 120 hours, as well as pharmacologic and nonpharmacologic remedies used. Results: Forty-seven (78.3%, 95% confidence interval [CI] 66.4–86.9), 37 (61.7%, 95% CI 49.0–72.9), and 35 (58.3%, 95% CI 45.7–69.9) patients reported no nausea (Numeric Rating Scale ⩽1), vomiting, or retching in the acute, delayed, and overall periods, respectively. Nausea was more frequent, more severe, and had a greater IDL than did vomiting and retching across the overall observation period; beyond 120 hours, 11 (18.3%, 95% CI 10.6–29.9) patients reported nausea and none reported vomiting, with a median IDL of 1/10 (interquartile range: 0.75–5.00; 95% CI 0–7.6). Metoclopramide (n = 57 administrations), dexamethasone (n = 28), eating small servings of food (n = 13), and aloe (n = 11) were the most commonly used rescue therapies. Conclusions: Future studies should set hard outcomes, such as the absence of any symptoms, as a primary end point, and these should be assessed across and beyond the 120-hour period.

Background Retroperitoneal sarcomas (RPS) should be surgically managed in specialized sarcoma centers. However, it is not clearly demonstrated if clinical outcome is more influenced by Center Case Volume (CCV) or by Surgeon Case Volume (SCV). The aim of this study is to retrospectively explore the relationship between CCV and SCV and the quality of surgery in a wide region of Northern Italy. Methods We retrospectively collected data about patients M0 surgically treated for RPSs in 22 different hospitals from 2006 to 2011, dividing them in two hospital groups according to sarcoma clinical activity volume (HCV, high case volume or LCV, low case volume hospitals). The HCV group (> 100 sarcomas observed per year) included a Comprehensive Cancer Center (HVCCC) with a high sarcoma SCV (> 20 cases/year), and a Tertiary Academic Hospital (HVTCA) with multiple surgeon teams and a low sarcoma SCV (≤ 5 cases/year for each involved surgeon). All other hospitals were included in the LCV group (

Although commonly thought of as two separate disease entities, cardiovascular diseases and cancer, the leading causes of death, possess various possible interactions, including a number of similar risk factors (e.g. obesity, diabetes, chronic inflammation). Each cardiologist should provide counseling for a correct lifestyle (diet, physical exercise, avoiding smoking and alcohol abuse); doing so, not only cardiovascular diseases, but also cancer could be prevented. Besides, intervention on diet, physical activity and smoking has been shown to be effective even in patients with known cancers. Many drugs used in cardiovascular prevention (i.e. aspirin, metformin, statins, and beta-blockers) have shown in vivo and in vitro promising pleiotropic properties, and, in observational studies, they were also effective in the prevention of some cancers, although this matter is controversial, emphasizing the need for interventional studies in the field of primary and secondary cancer prevention. Considerable interest has emerged regarding the potential adjuvant chemotherapeutic use of these drugs, but real-world epidemiological data remain inconclusive. In this review, we explore the risk factors common to both cardiovascular diseases and cancer, as well as the role of preventive cardiology treatments, highlighting the related major epidemiologic studies and potential biological mechanisms.

Quality issue The definition of clinical pathways (CPs) and their application are heterogeneous. Each center is used to choose whether to adopt this instrument or not and to variably conceive its features We consider CPs as the necessary description of the cancer patient journey and we emphasize their role as the user view of clinical processes rather than a local translation of guidelines. Choice of solution We proposed a unique CPs model for all the centers of our regional network, with the aim of making CPs accountable and comparable. We also established a central quality evaluation. Implementation Through a multi-step process, the model was proposed to the 22 Regional centers. Landmark characteristics of the project were: the involvement of hospital administrations; reference to a unique set of guidelines; a peer-review and open evaluation. Evaluation Of the 374 expected CPs, 253 (68%) were received and evaluated. A median number of 131 items were the object of evaluation in each hub center and 77 in each spoke center. About 79.5% items were considered well described, 15.5% were absent and 5.0% partially described. The median percentage of fulfilled indicators was 85.6% in hub CPs and 82.2% in spoke CPs. Although, not all diseases were equally covered through the territory a high degree of homogeneity and a good quality of compilation were achieved. Lessons learned The project was shown to be feasible and achieved its goal. We suggest this process as a functional way for building uniform cancer CPs.

BackgroundIn the northwestern Italian region of Piedmont, current statistics on hospitalizations show that surgical treatment for ovarian cancer (OC) is taking place in many small hospitals, as opposed to a more centralized approach. A population-based clinical audit was promoted to investigate whether OC is being managed according to clinical guidelines, identify determinants of lack of adherence to guidelines, and evaluate the association between adherence to guidelines and survival.Patients and MethodsResidents diagnosed with OC in 2009 were identified in the regional hospital discharge records database. All hospitalizations within 2 years from diagnosis were reviewed. Patients were classified according to their initial pattern of care, defined as “with curative intent” (CIPC) if including debulking surgery aimed at maximal cytoreduction. Adherence to guidelines for surgery and chemotherapy and the effects of this adherence on OC survival were investigated with logistic regression and Cox models.ResultsThe final study sample consisted of 344 patients with OC, 215 (62.5%) of whom received CIPC. Increasing age, comorbidities, and metastases were negatively associated with receiving CIPC. In the CIPC group, surgical treatment was adherent to guidelines in 35.2%, whereas chemotherapy was adherent in 87.8%. Surgical treatment that was adherent to guidelines [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.45–1.15] and absence of residual tumor (HR, 0.55; 95% CI, 0.32–0.94) were associated with better survival in the CIPC group, and chemotherapy that was adherent to guidelines was associated with a significant reduction in the risk of death (HR, 0.49; 95% CI, 0.28–0.87).ConclusionsResults support the need to reorganize the clinical pathway of patients with OC in the Piedmont Region and the need for better adherence to current guidelines.

Background Effective management of pain associated with metastatic bone disease is paramount in the care of cancer patients. Bisphosphonates are recommended in treating skeletal complications and there is evidence that they also control pain.

The status of axillary nodes is the most important prognostic factor in breast cancer to select patient subgroups for adjuvant chemotherapy; the current standard of care for surgical management of invasive breast cancer is complete removal of the tumor by either mastectomy or lumpectomy followed by axillary lymph node dissection (ALND). The recent introduction of intraoperative lymphatic mapping and sentinel lymph node biopsy (SLND) represents a major new opportunity for appropriate and less invasive surgical management of many tumors. There is an almost uniformly enthusiasm concerning the potential of this technique in breast carcinoma management, shown by published data. A peculiar attention to the so-called “sentinel node debate” in breast cancer surgery is a constant in the last years issues of the major medical journals. Even patients have become more aware about medical enthusiasm and their request of concise information on the topic and the possibilities of this approach is an increasing reality in medical practice. The aim of this paper is to review recent literature to offer an overview about the main controversial methodological aspects and a wide analysis of reported results. The most significative international literature papers from Medline were retrieved from 1993 to September 1999, and 4782 procedures were analysed. This extensive review of the literature has confirmed accuracy, feasibility and reliability of the SN detecting technique in axillary mapping. Provided a good proficiency in SN localisation and pathological evaluation, human resources and efforts should be mainly focused on its clinical validation as an alternative to ALND instead of on further phase I–-II clinical studies.

Introduction Gastrointestinal metastases from breast cancer are rare. One large series reported a rate of 0.7% of gastrointestinal metastatic manifestations from breast cancer, but its true incidence could be underestimated. Here we report a case of bowel obstruction caused by sigmoid metastases from breast cancer and describe its relevance to histological origin and clinical practice. Methods The clinical course and histopathology of the case are reviewed and compared with reports of similar cases in the literature. Results An 80-year-old woman presented with bowel obstruction. Her medical history included infiltrating lobular breast cancer treated with left radical mastectomy 25 years before the current presentation; 13 years later bone metastases developed and were treated with hormone therapy. In 2003 the patient came to our emergency department because of symptoms of bowel obstruction. A computed tomography (CT) scan revealed a mass in the distal sigmoid causing the obstruction. A colostomy was performed, followed by a second operation completed with Hartmann's procedure. Histological examination revealed metastases from invasive lobular carcinoma. The patient was discharged 45 days postoperatively and died 9 months later because of disease progression. Conclusions Although gastrointestinal metastases from breast cancer are rare, patients with diagnosed breast cancer, particularly invasive lobular carcinoma, should be regularly followed up with endoscopy, CT, endosonography and PET-CT when abdominal symptoms are present. This could permit early diagnosis of gastrointestinal metastases and improve treatment planning.

Background Trastuzumab is a monoclonal antibody selectively directed against Her2 and approved for the treatment of Her2 overexpressing breast cancer patients. Its proposed mechanisms of action include mediation of antibody-dependent cellular cytotoxicity (ADCC) by triggering FcγRIII on natural killer (NK) cells. This study addresses the correlation between overall NK function and trastuzumab's clinical activity. Subjects and methods Clinical and immunological responses were assessed in 26 patients receiving trastuzumab monotherapy as maintenance management after chemotherapy (8 mg/kg load and then standard doses of 6 mg/kg every 3 weeks). Cytotoxic activity against the MHC class I-negative standard NK target K562 cell line and HER2-specific ADCC against a trastuzumab-coated Her2-positive SKBR3 cell line were assessed in peripheral blood mononuclear cells (PBMC) harvested after the first standard dose. After six months, seventeen patients were scored as responders and nine as non-responders according to the RECIST criteria, while Progression-Free Survival (PFS) was calculated during a 12 months follow-up. Results The responders had significantly higher levels of both NK and ADCC activities (p < 0.05) that were not different from those of eleven normal controls. The NK activity of the non-responders was significantly (p < 0.05) lower than that of the normal controls. At twelve months, there was a marked correlation between PFS and NK activity only. PFS was significantly longer in patients with high levels of NK activity, whereas its pattern was unrelated to high or low ADCC activity. Conclusion One of the mechanisms of action of trastuzumab is NK cell-mediated ADCC lysis of the Her2-positve target cell. We show here that its potency is correlated with the short-term response to treatment, whereas longer protection against tumor expansion seems to be mediated by pure NK activity.

Background: Treating patients with anthracycline- and taxane-pretreated metastatic breast cancer is challenging. This study evaluated the activity and safety of a combination of cisplatin and capecitabine in this setting. Patients and Methods: Thirty-nine consecutive patients entered the study. All had experienced failures or relapse after previous treatment with anthracyclines and taxanes plus/minus other chemotherapeutic regimens. The present treatment consisted of intravenous cisplatin 20 mg/m2 every week for 6 weeks, followed by 1 week of rest, and oral capecitabine 1,000 mg/m2 twice daily for 14 days, followed by a 7-day rest period. Results: Objective response was obtained in 14 patients (35.9%), with complete remission in 3 (7.7%). Median time to progression was 5.2 months and survival was 10.9 months in the entire population and 8.7 and 16.5 months in the responding patients, respectively. The dose-limiting toxicity for the regimen was leucopenia, while gastrointestinal discomfort was the most frequent cause of capecitabine reduction or delay. Conclusions: The cisplatin and capecitabine combination regimen is active and manageable. It seems to be non-cross resistant to anthracyclines and taxanes.

To evaluate the feasibility and activity of gemcitabine and vinorelbine as a second/third-line approach in patients with advanced breast cancer.Entered into the study were 51 consecutive patients. All had been previously treated with anthracyclines. Of these 51 patients, 36 had experienced failure or relapse after one chemotherapy line for advanced disease, and 15 after two chemotherapy lines. The dominant sites of involvement were brain in 4 patients (7.8%), liver in 22 (43.2%), lung in 10 (19.6%), bone in 10 (19.6), and soft-tissue in 5 (9.8%). Treatment consisted of vinorelbine 25 mg/m(2) and gemcitabine 1000 mg/m(2) administered on days 1 and 8 every 21 days.The scheme was well tolerated. Grade 3/4 neutropenia was observed in 11% of patients. Grade 3 nausea and vomiting occurred in 6%, and grade 2 neurotoxicity in 6%. No patients experienced grade 3/4 alopecia. The median relative dose intensity was 94.6% (49.7-100%) and 90.0% (23.1-100%) for vinorelbine and gemcitabine, respectively. Two patients (3.9%) were not evaluable for disease response, 4 (7.8%) attained a clinical complete response, 13 (25.5%) a partial response (for an overall response rate of 33.3%, 95% coefficient interval 20.0-46.0%), 23 (45.2%) showed stable disease, and 9 (17.6%) progressed. The median time to progression of responding patients was 10.8 months, and the median overall survival of the entire population was 17.8 months.Vinorelbine and gemcitabine is a manageable scheme with moderate activity in pretreated patients with advanced breast cancer.

The available data on the natural history of pheochromocytomas and paragangliomas after radical surgery are heterogeneous and discordant. The aim of our retrospective multicenter study was to find predictors of recurrence in patients with pheochromocytomas and sympathetic paragangliomas submitted to radical surgery in Piedmont (a region in northwest Italy). We collected data from 242 patients diagnosed between 1990 and 2016. Forty-two patients (17.4%) had disease recurrence. Multivariate analysis showed that genetic mutation (HR = 3.62; 95% CI 1.44-9.13; p = 0.006), younger age (HR = 0.97; 95% CI 0.95-0.99; p = 0.031) and larger tumor size (HR = 1.01; 95% CI 1.00-1.02; p = 0.015) were independently associated with a higher recurrence risk of pheochromocytoma and paraganglioma; in pheochromocytomas, genetic mutation (HR = 3.4; 95% CI 1.00-11.48; p = 0.049), younger age (HR = 0.97; 95% CI 0.94-0.99; p = 0.02), higher tumor size (HR = 1.01; 95% CI 1.00-1.03; p = 0.043) and PASS value (HR = 1.16; 95% CI 1.03-1.3; p = 0.011) were associated with recurrence. Moreover, tumor size was the only predictor of metastatic pheochromocytoma and paraganglioma (HR = 4.6; 95% CI 1.4-15.0; p = 0.012); tumor size (HR = 3.93; 95% CI 1.2-16.4; p = 0.026) and PASS value (HR = 1.27; 95% CI 1.06-1.53; p = 0.007) were predictors of metastatic pheochromocytoma. In conclusion, our findings suggest that the recurrence of pheochromocytoma and sympathetic paraganglioma develops more frequently in younger subjects, patients with a family history of chromaffin tissue neoplasms, mutations in susceptibility genes, larger tumors and higher values of PASS. We recommend genetic testing in all patients with PPGL and strict follow-up at least on an annual basis.