A comparison of chemo-free strategy with G-CSF plus plerixafor on demand versus intermediate-dose cyclophosphamide and G-CSF as PBSC mobilization in newly diagnosed multiple myeloma patients: An Italian explorative cost Analysis.

BACKGROUND: Upfront single or tandem ASCT still represents an integral part of treatment for patients with multiple myeloma. The combination of intermediate dose (ID) - cyclophosphamide plus G-CSF, has been considered the standard method as mobilization regimen. No prospective randomized clinical trials have compared efficacy and costs using ID - cyclophosphamide against a chemo-free mobilization strategy with G-CSF and plerixafor on demand. METHODS: A prospective single arm of 20 patients enrolled in three Italian Centers mobilized with G-CSF plus plerixafor on demand was compared with a retrospective historical control arm of 30 patients mobilized with ID - cyclophosphamide (4 g/sqm) and G-CSF. Costs of the prospective arm was compared with the ones of the retrospective control arm with the aim to collect ≥4 × 106/kg CD34 + . The exploratory cost analysis was performed using microcosting specific inputs of G-CSF plus plerixafor on demand versus ID - cyclophosphamide + G-CSF considering pre-apheresis, peri-apheresis and post-apheresis session. RESULTS: Mobilization with ID - cyclophosphamide and G-CSF resulted in a significantly higher CD34+ peak mean on day 1 yield (119 CD34+ µL vs 67.3; p = 0.06) and in total average CD34+ yield (mean collection 10.6 × 106/kg vs 5.8 × 106/kg; p = 0.004) compared to patients mobilized with G-CSF and plerixafor. There was no significant differences (p = 0.36) in the two groups of patients collecting ≥ 4 million CD34+/Kg with ID - cyclophosphamide and G-CSF (93.3 %) vs G-CSF and plerixafor (90.0 %). None of the patients undergoing G-CSF and plerixafor mobilization had febrile neutropenia compared with 7 patients who received ID - cyclophosphamide and G-CSF (0% vs 23 %, p = 0.03) who had a median of 5 days hospitalization (range 4-6). All patients proceeded to ASCT with a mean of 3.6 CD34+/kg infused for G-CSF and plerixafor arm and 4.4 CD34+/kg for the ID - cyclophosphamide + GCSF group (p = 0.37) with a median time to ANC and PLT engraftment not different in the two groups. Total costs of a mobilizing strategy using a combination of G-CSF and plerixafor on demand was 12.690 euros compared to 16.088 euros with ID - cyclophosphamide and G-CSF (p = 0.07); in particular, mobilization cost components were significantly lower for G-CSF and plerixafor vs G-CSF and ID - cyclophosphamide for hospital stay (3080 euros vs 9653 euros; p < 0.001) whereas for mobilizing agent, there was a significative difference with 5470 euros for G-CSF and plerixafor use due to the cost of plerixafor compared with 1140 euros for ID - cyclophosphamide and G-CSF treatment (P = 0.001). CONCLUSIONS: Our data demonstrate that in patients with multiple myeloma eligible for ASCT, a chemo-free mobilization with G-CSF and plerixafor on demand is associated with efficacy in PBSC collection and optimal safety profile with similar average costs when compared to a chemo-mobilization with ID - cyclophosphamide. A prospective randomized multicenter study could address which is the most cost-effective strategy for this setting of patients. CLINICAL TRIAL REGISTRY: Eudract Number EudraCT 2013-004690-27.

Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation.

BACKGROUND: The role of primary tumour surgery in pancreatic neuroendocrine tumours (PNETs) with unresectable liver metastases is controversial and international guidelines do not recommend surgery in such cases. Resectability of the primary tumour has never been considered in outcome comparisons between operated and non-operated patients. METHODS: From two institutional prospective databases of patients affected by PNET and unresectable liver metastases, 63 patients who underwent a left-pancreatectomy at diagnosis were identified and compared with a group of 30 patients with a potentially resectable but not-resected primary tumour located in the body or tail. The endpoint was overall survival (OS). RESULTS: The two groups significantly differed at baseline with regard to liver tumour burden Ki-67 labelling index, site of pancreas, results of the 18FDG PET-CT and age. In the operated patients, surgical morbidity comprised 7 cases of pancreatic fistula. Postoperative mortality was nil. Median OS for patients undergoing left-pancreatectomy was 111 months vs 52 for the non operated patients (p = 0.003). At multivariate analysis after propensity score adjustment, no surgery as well as liver tumour burden>25% and higher Ki-67 index were associated with an increased risk of death during follow-up. In patients with unresectable primary tumour, OS was similar in comparison to that in the resectable but non-resected patients, and significantly worse than that in the resected patients (p = 0.032). CONCLUSION: In PNETs located in the body or tail and diffuse liver metastases distal pancreatectomy may be justified in selected patients. Randomized studies may be safely proposed in future on this topic.

Risk of second primary malignancies among 1537 melanoma patients and risk of second primary melanoma among 52 354 cancer patients in Northern Italy.

BACKGROUND: The number of melanoma survivors has been increasing for decades due to early diagnosis and improved survival. These patients have an increased risk of developing a second primary cancer (SPC); also, melanoma is frequently diagnosed among patients firstly diagnosed with an extracutaneous malignancy. OBJECTIVE: We evaluated the risk of developing a SPC among 1537 melanoma patients, and the risk of second primary melanoma (SPM) in 52 354 extracutaneous cancer patients, who were treated at the European Institute of Oncology in Milan, Italy, during 2000-2010. MATERIAL AND METHODS: We calculated standardized incidence ratios (SIR) by applying gender-, age-, year- and region-specific reference rates to the follow-up time accrued between the diagnosis of the first and the second primary malignancies. RESULTS: Seventy-six SPC were diagnosed during a median follow-up of 4 years, of which 49 (64%) during the first 2 years upon melanoma diagnosis. The SIR was increased for cancer of breast (4.10, 95% CI 2.79-6.03), thyroid (4.67, 95% CI 1.94-11.22), brain (6.13, 95% CI 2.30-16.33) and for non-Hodgkin lymphoma (3.12, 95% CI 1.30-7.50). During a median follow-up of 4 years, 127 SPM were diagnosed: thick lesions were less frequent than for melanoma diagnosed as first cancer. The SIR was increased for cancer of breast (5.13, 95%CI 3.91-6.73), thyroid (16.2, 95%CI: 5.22-50.2), head and neck (5.62, 95%CI 1.41-22.50), soft tissue (8.68, 95%CI 2.17-34.70), cervix (12.5, 95% CI 3.14-50.20), kidney (3.19, 95%CI 1.52-6.68), prostate (4.36, 95%CI 2.63-7.24) and acute myeloid leukaemia (6.44, 95%CI 2.42-17.20). CONCLUSIONS: The most likely causes of these associations are the clustering of lifestyle risk factors in the same subgroups of population, mainly on a sociocultural basis and surveillance bias. This raises important questions about how to best follow cancer survivors by avoiding an inefficient use of resources and an excessive medicalization of these patients' lives.

Responsiveness of clinical outcome measures in Charcot-Marie-Tooth disease.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed. METHODS: The relative responsiveness of clinical scales of the Italian-UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness). RESULTS: Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM -0.31 and -0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28). CONCLUSIONS: Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.

Long-term effects of inhaled budesonide on screening-detected lung nodules.

BACKGROUND: A previously carried out randomized phase IIb, placebo-controlled trial of 1 year of inhaled budesonide, which was nested in a lung cancer screening study, showed that non-solid and partially solid lung nodules detected by low-dose computed tomography (LDCT), and not immediately suspicious for lung cancer, tended to regress. Because some of these nodules may be slow-growing adenocarcinoma precursors, we evaluated long-term outcomes (after stopping the 1-year intervention) by annual LDCT. PATIENTS AND METHODS: We analyzed the evolution of target and non-target trial nodules detected by LDCT in the budesonide and placebo arms up to 5 years after randomization. The numbers and characteristics of lung cancers diagnosed during follow-up were also analyzed. RESULTS: The mean maximum diameter of non-solid nodules reduced significantly (from 5.03 mm at baseline to 2.61 mm after 5 years) in the budesonide arm; there was no significant size change in the placebo arm. The mean diameter of partially solid lesions also decreased significantly, but only by 0.69 mm. The size of solid nodules did not change. Neither the number of new lesions nor the number of lung cancers differed in the two arms. CONCLUSIONS: Inhaled budesonide given for 1 year significantly decreased the size of non-solid nodules detected by screening LDCT after 5 years. This is of potential importance since some of these nodules may progress slowly to adenocarcinoma. However, further studies are required to assess clinical implications. CLINICAL TRIAL NUMBER: NCT01540552.

Is overwork weakness relevant in Charcot-Marie-Tooth disease?

BACKGROUND: In overwork weakness (OW), muscles are increasingly weakened by exercise, work or daily activities. Although it is a well-established phenomenon in several neuromuscular disorders, it is debated whether it occurs in Charcot-Marie-Tooth disease (CMT). Dominant limb muscles undergo a heavier overload than non-dominant and therefore if OW occurs we would expect them to become weaker. Four previous studies, comparing dominant and non-dominant hand strength in CMT series employing manual testing or myometry, gave contradictory results. Moreover, none of them examined the behaviour of lower limb muscles. METHODS: We tested the OW hypothesis in 271 CMT1A adult patients by comparing bilateral intrinsic hand and leg muscle strength with manual testing as well as manual dexterity. RESULTS: We found no significant difference between sides for the strength of first dorsal interosseous, abductor pollicis brevis, anterior tibialis and triceps surae. Dominant side muscles did not become weaker than non-dominant with increasing age and disease severity (assessed with the CMT Neuropathy Score); in fact, the dominant triceps surae was slightly stronger than the non-dominant with increasing age and disease severity. DISCUSSION: Our data does not support the OW hypothesis and the consequent harmful effect of exercise in patients with CMT1A. Physical activity should be encouraged, and rehabilitation remains the most effective treatment for CMT patients.

Implementation of the 'Sapere Migliora' information aid for newly diagnosed people with multiple sclerosis in routine clinical practice: a late-phase controlled trial.

BACKGROUND: The SIMS-Trial showed that the 'Sapere Migliora' information aid (IA) for newly diagnosed people with multiple sclerosis (PwMS) effectively improved patient knowledge and satisfaction with care. OBJECTIVES: The objectives of this paper are to assess the effectiveness of the IA in clinical practice and to compare the whole IA with the take-home booklet/website component alone. METHODS: After updating the IA and replacing the CD with a website, a prospective, open-label non-randomised controlled trial compared the whole IA (group A, five SIMS-Trial centres) to take-home (group B, 16 centres). One month after the intervention, participants completed the MS Knowledge Questionnaire (MSKQ), care satisfaction questionnaire (COSM-R) (primary study outcomes), Hospital and Anxiety Depression Scale, and ad hoc questionnaire appraising the IA. RESULTS: We enrolled 159 newly diagnosed PwMS (May 2012-March 2013). Drop-outs were four of 77 (5%, group A) and 11/82 (13%, group B). Primary endpoint (highest tertile both for MSKQ and COSM-R section 2 scores) was achieved by 38/77 (49%) group A and 33/82 (40%) group B (p = 0.25). Attainment of secondary outcomes was also similar between groups. CONCLUSIONS: This study shows that the entire IA is not superior to the booklet/website alone, and that both are comparable in efficacy to the intervention arm of the SIMS-Trial. TRIAL REGISTRATION NUMBER: ISRCTN78940214.

The choice of whether to participate in a phase I clinical trial: increasing the awareness of patients with cancer. An exploratory study.

OBJECTIVE: In a previous study, we found that patients who were offered the possibility of participation in a clinical trial had unexpressed concerns and fears that prevented them from making free or fully knowledgeable choices about their trial participation. In a selected population of patients who were offered participation in a phase I trial, we prospectively investigated whether a face-to-face discussion about their unexpressed fears might lead to a more conscious decision about whether to accept/refuse participation in the trial. METHODS: After the presentation of the trial, a questionnaire was administered to assess the presence of specific fears. Before the patients decided whether to participate in the trial, they discussed any fears that they had; finally, the impact of the discussion on the patients' choice to participate was evaluated. RESULTS: The majority (86%) of the patients thought that physicians conduct clinical trials for scientific interest, 13% felt exploited as 'guinea pigs' and 20% believed they were offered participation because they had no further hope for improvement. These existing fears were not elicited during the trial interview because the patients were themselves unaware of having them (28%) and because of fear of the doctors (3%). The possibility of discussing these fears was felt as an opportunity and made patients feel more conscious (92%) and freer (97%) when making their choice. CONCLUSIONS: Recognising and discussing misconceptions and fears, often unexpressed, make patients freer and more aware when facing the choice of whether or not \to participate in a phase I clinical trial.

Filgrastim XM02 (Tevagrastim®) after autologous stem cell transplantation compared to lenograstim: favourable cost-efficacy analysis.

PURPOSE: Granulocyte colony-stimulating factors (G-CSFs), filgrastim and lenograstim, are recognised to be useful in accelerating engraftment after autologous stem cell transplantation. Several forms of biosimilar non-glycosylated G-CSF have been approved by the European Medicines Agency, with limited published data supporting the clinical equivalence in peripheral blood stem cell mobilisation and recovery after autologous stem cell transplantation. METHOD: With the aim of comparing cost-effective strategies in the use of G-CSF after autologous stem cell transplantation, we retrospectively evaluated 32 patients consecutively treated with biosimilar filgrastim XM02 (Tevagrastim) and 26 with lenograstim. All patients received G-CSF (biosimilar or lenograstim) at a dosage of 5 mcg/kg/day subcutaneously from day 5 to absolute neutrophil count of 1500/mmc for three days. RESULTS: The median time to absolute neutrophil count engraftment was 11 days for the filgrastim XM02 group and 12 days for the lenograstim group. As for platelets recovery, the median time was 12 days in both groups. The median number of G-CSF vials used for patients was 9.5 for Tevagrastim and 10.5 for lenograstim, reflecting a mean estimated cost of about 556.1 euros for Tevagrastim versus 932.2 euros for lenograstim (p< 0.001). The median days of febrile neutropenia were 1.5 and 1 for filgrastim XM02 and lenograstim, respectively. No adverse event related to the use of XM02 filgrastim was recorded. CONCLUSION: In our experience, filgrastim XM02 and lenograstim showed comparable efficacy in shortening the period of neutropenia after cytoreduction and autologous stem cell transplantation, with a favourable cost effect for filgrastim XM02.

Neoadjuvant chemotherapy prior to pelvic exenteration in patients with recurrent cervical cancer: single institution experience.

OBJECTIVES: The aim of the study is to evaluate the response to neoadjuvant chemotherapy (NACHT) of patients with recurrent cervical cancer who were poor candidates for pelvic exenteration (PE), and the impact on DFS and OS. METHODS: A retrospective data collection extracted from medical records of 61 patients submitted to pelvic exenteration was performed: 30 underwent up-front exenterative procedure whereas 31 received NACHT. RESULTS: The median tumor size was significantly (P=0.0006) larger in the NACHT group compared to the up-front PE one (43.9 mm vs 28 mm), and a significant (P=0.04) higher percentage of patients (45 vs 20%) had lateral pelvic wall invasion in the NACHT group. No statistically significant difference in early and late complications was observed in the two groups. Median overall survival in study population was 42.9 months (95% CI: 22.2, 180.8). Median overall survival times as well as recurrence free survival times were not significantly different between NACHT (42.9 months and 36.1 months for OS and DFS respectively) vs. No NACHT (111.9 months and 48.1 months for OS and DFS respectively). There was an overall significant difference in DFS between negative and positive margins but the curves were similar for NACHT and up-front PE groups stratified by resection margin status. CONCLUSIONS: In our series, though small and retrospective, NACHT prior to PE represents a feasible therapeutic option without intra-operative and early post-operative mortality or worsening of early and late complication rate and with acceptable long-term survival and DFS for recurrent cervical cancer patients who are poor candidates for up-front pelvic exenteration.

Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: correlation with pathological outcome.

OBJECTIVE: The quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease. METHODS: Three hundred and forty-nine pre- and post-menopausal women, aged 18 years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample. RESULTS: Median serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p<0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p=0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients. CONCLUSIONS: Data presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.

Self-assessed health status changes in a community cohort of people with multiple sclerosis: 11 years of follow-up.

BACKGROUND AND PURPOSE: Few data are available on the health status of people with multiple sclerosis (PwMS) in the community. We assessed changes in self-perceived health status and health related quality of life of a community-based cohort of PwMS over a decade, and identified predictors of such changes. METHODS: In 1999 we started the POSMOS study (Postal Survey of Self-Assessed Health of MS Adults and their Significant Others) on a random sample of 251 adults with MS from the Milan area (mean age 42 years, range 18-71 years), and prospectively assessed changes in self-perceived health status over 11 years. Participants completed the Multiple Sclerosis Quality-of-Life-54 (MSQOL-54) and a general/clinical questionnaire. We re-assessed the cohort in 2004 and 2010, sending the same questionnaires plus the Chicago Multiscale Depression Inventory. RESULTS: There were 205 (86%) respondents in 2004, 171 (74%) in 2010; 28 (11%) died during the study. Severely impaired [self-determined Expanded Disability Status Scale (EDSS) > 6.5] increased from 19% to 32%. One-fifth remained fully ambulatory (EDSS <4.0): 25% women (median age 44 years [interquartile range, IQR 39-53], median years from diagnosis 16 [IQR 12-19]); and 17% men (median age 40 years [IQR 38-45], median years from diagnosis 14 [IQR 12-17]). Changes in MSQOL-54 composite scores were negligible; but among individual scales, change in health, cognitive function and general health worsened, and social function and emotional wellbeing improved significantly. Depressive symptoms were high and stable. CONCLUSIONS: Multiple sclerosis had a pervasive but inhomogeneous impact on the lives of our MS sufferers. Notwithstanding overall clinical deterioration and aging, hospital admissions and medical consultations decreased, suggesting reduced use of health care resources. By contrast, housing adaptations and home care increased, psychological burden was high and self-perceived cognitive functioning worsened.

Lesiones tendinosas en medicina del deporte: ciencias básicas aplicadas al tratamiento actual / Tendinopathy in sports medicine: the basic sciences and current management

Las lesiones del tendón, denominadas “Tendinosis” son muy frecuentes en la práctica de deportistas de alto rendimiento y recreacionales. Están dentro de las patologías de sobreuso que representan cerca del 60 por ciento de las lesiones deportivas y se relacionan con una sobrecarga cíclica repetidas. Los tendones más afectados del organismo son el rotuliano, aquiliano y manguito rotador. Estudios demuestran que la condición de tendinosis aumenta significativamente su incidencia en relación a la edad; sexo masculino y obesidad. El incremento de la vascularización y terminaciones nerviosas, asociado a un aumento en la producción local de neurotransmisores explicaría la presencia de dolor crónico en las tendinosis. Tendinosis implica una pérdida progresiva de la capacidad de respuesta del tendón para una adecuada regeneración o cicatrización cuando es sometido a una carga cíclica de gran volumen en forma reiterada. La carga cíclica alta repetida induce 1- Estrés oxidativo y apoptosis. 2- Genes cartílago sustituto. Histológicamente esta falla en la respuesta reparativa se refleja en descontrolada proliferación de Tenocitos, disrupción de fibras colágenas, alteraciones en la matriz extracelular, incremento en el fenómeno de apoptosis y cambios en la homeostasis de las Metalo-proteinasas. Se inicia la destrucción de la matriz, aumenta la vascularización y terminaciones nerviosas y el tendón presenta dolor y mecánicamente respuestas a la carga inferiores a un tendón sano. Existe una gran cantidad de opciones de tratamientos pero el objetivo de este artículo es presentar aquellas opciones que nuestro equipo de trabajo aplica, basada en las ciencias básicas y últimos hallazgos con evidencia científica 1- Ejercicios excéntricos asociados a aplicación de ondas de choque radiales han demostrado alto grado de éxito 2- Uso de sustancias esclerosante (polidocanol) y concentrado...

Tendinopathies account for a substantial proportion of overuse injuries associated with sports1 and are a common cause of disability. Most major tendons, such as the Achilles, patellar, rotator cuff, and forearm extensor tendons (among others), are vulnerable to overuse, which induces pathological changes in the tendon. Tendinopathy has an increased incidence with age and the male gender and with obesity. Excessive long-distance running, intensity, and hill work are risk factors for acute. Tendinopathy is a failed healing response of the tendon. The aim of this review is to identify recent advances in the understanding of tendinopathy, particularly from a cell and molecular biology perspective. There has been much new information and there are many gaps in our understanding of the pathogenesis of tendinopathy. The current hypothesisis that tendinopathy is induced when tendon cells experience a large volume of repetitive load. High doses of cyclical strain induce genes for two major pathways ) oxidative stress- apoptosis; and cartilage like genes. The tendon cells become rounded and apoptotic and produce a matrix that contains less Type I collagen and is more cartilaginous and ‘immature’’ in nature. The therapeutic options with clinical evidence are 1- Combining eccentric training and shock wave therapy produces higher success rates compared with eccentric loading alone or shock wave therapy alone. 2- The use of injectable substances such as platelet-richplasma, autologuos blood, polidocanol, corticosteroids, and aprotinin in and around tendons is popular, but there isminimal clinical evidence to support their use: 3- The aim of operative treatment is to excise fibrotic adhesions, remove areas of failed healing, and make multiple longitudinal incisions in the tendon to detect intratendinous lesions and to restore vascularity and possibly stimulate the remaining viable cells to initiate cell matrix response...

Why do women accept to undergo a nipple sparing mastectomy or to reconstruct the nipple areola complex when nipple sparing mastectomy is not possible?

In a retrospective study, we investigated the reasons why women accepted to undergo a nipple sparing mastectomy (NSM) and why women who could not keep their nipple areola complex (NAC) decided to reconstruct it. We intended to investigate whether keeping the NAC plays a psychological role, to state possible advantages of NSM. Between 2004 and 2006, 310 women with NAC sparing and 143 patients with successive NAC reconstruction were mailed a single open-ended question at follow-up 12 months after final breast reconstruction surgery or final NAC reconstruction with tattoo. The purpose was to explore personal motivations that drove women to accept NSM or to perform a NAC tattoo reconstruction. Responses were classified into 11 categories by five reviewers. We performed an analysis of the relative frequency of emerging issues. Socio-demographic and clinical data were collected. Among the patients who responded to the open-ended question, 190 patients preserved their NAC, and 100 patients received postponed NAC reconstruction. Women in the NSM group were significantly younger (P = 0.02), more highly educated (P < 0.0001), and more frequently lived in Northern Italy (P = 0.03). The reasons for accepting NSM were more frequently related to body image satisfaction and integrity of the body (P = 0.002), reduction of psychological distress (P = 0.003), and surgeon's influence (P < 0.0001). Esthetic reasons were highly associated to the control group. These results help us to better understand the psychological impact of NAC sparing versus NAC reconstruction. NSM was accepted because it was perceived as a technique that preserved the integrity of the body, reduced the feeling of mutilation, improved the breast cosmetic results, and reduced psychological distress regarding the loss of the breast.

Health-related quality of life and depressive symptoms in significant others of people with multiple sclerosis: a community study.

BACKGROUND AND PURPOSE: Uncertain prognosis and modest treatment efficacy make multiple sclerosis (MS) a particularly difficult disease to adjust to for both patients and their significant others (SOs). Few studies have assessed health-related quality of life (HRQOL) and depressive symptoms in SOs of people with MS in the community. We assessed, and identified predictors of, HRQOL and depression in SOs of adults with MS. METHODS: POSMOS (postal survey of self-assessed health in MS adults and SOs) is a longitudinal survey on a random sample of 251 people with MS in the Milan area. In 2010, SOs and contemporaneous controls completed the SF-36 and Chicago Multiscale Depression Inventory (CMDI). RESULTS: Overall, 142 SOs (mean age 53.1 years; 50% women, 65% partners) and 120 controls (similar to SOs for sex and education, but older) participated. By multivariable modeling of the SO plus control population, SF-36 vitality was lower in SOs (proportional odds ratio 0.45; 95% confidence interval 0.28-0.70), women (0.41; 0.27-0.64), and older subjects (0.98; 0.97-0.99). SF-36 mental health was also lower in SOs (0.62; 0.40-0.96) and women (0.43; 0.28-0.67). Regarding MS characteristics associated with HRQOL and depression in SOs, severe disability [Expanded Disability Status Scale (EDSS > 6.5)] had no effect, whilst depressive symptoms (pathologic CMDI) negatively influenced most SF-36 and all CMDI scores in SOs. CONCLUSIONS: SOs had significantly lower vitality and psychological well-being than controls, identifying a burden in being the companion of a person with MS. This burden was unrelated to physical compromise but associated with depressive symptoms in MS.

Comparison of oral polyethylene glycol plus a large volume glycerine enema with a large volume glycerine enema alone in patients undergoing colorectal surgery for malignancy: a randomized clinical trial.

AIM: Recent meta-analyses and randomized clinical trials have concluded that mechanical bowel preparation (MBP) before elective colorectal surgery is not associated with a reduction of surgical site infection (SSI). The aim of this randomized clinical trial was to evaluate the impact of preoperative MBP for colon and rectal cancer surgery in comparison with a single glycerine enema. METHOD: Patients scheduled for radical colorectal resection for malignancy with primary anastomosis were randomized to preoperative MBP (4 l of polyethylene glycol) (group 1, 114 patients) plus a glycerine 5% enema (2 l) or a single glycerine 5% enema (2 l) (group 2, 115 patients). The postoperative incidence of SSI was recorded prospectively. Patients undergoing minimally invasive surgery (laparoscopy or robotic) accounted for 55 and 51 in groups 1 and 2 respectively. RESULTS: In all, 229 patients were included in the study, 114 in group 1 and 115 in group 2. At least one SSI was reported in 16 (14.0%) group 1 and in 20 (17.8%) group 2 patients (P=0.475). Perioperative mortality was nil. The incidence of SSI was comparable also in the 73 patients who had a low anterior resection (seven of 33 vs eight of 40, P=1.000), and for the 106 patients who underwent a minimally invasive procedure (nine of 55 vs four of 51, P=0.241). CONCLUSION: A single large-volume glycerine enema is effective bowel preparation before colorectal resection whether performed by an open or minimally invasive technique.

Optimizing clinical care in patients with advanced soft tissue sarcoma: a phase II study of a new schedule of high-dose continuous infusion ifosfamide and doxorubicin combination.

BACKGROUND: Ifosfamide and doxorubicin combination is an active regimen for patients with advanced soft tissue sarcomas (STS) but is burdened by high toxicity. A phase II trial was designed to assess the activity of continuous infusion ifosfamide and doxorubicin combination. PATIENTS AND METHODS: Thirty-four chemotherapy-naive patients with advanced STS were treated with ifosfamide (13 g/m(2)/12 days as continuous infusion) and doxorubicin (75 mg/m(2) on day 8) every 28 days with granulocyte colony-stimulating factor. RESULTS: The major toxicity was hematological: grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 63, 30 and 12% of patients, respectively. The disease control rate was 68% and the median time to progression was 7.1 months. Among leiomyosarcomas, 2 partial responses and 4 stable diseases were observed. CONCLUSIONS: Our study confirms that the ifosfamide and doxorubicin combination has a very low non-hematological toxicity profile. This regimen attained a high disease control rate with moderate activity. Further investigation into leiomyosarcoma is warranted.

Tissue microarrays in diffuse large B-cell lymphomas: are they really able to identify distinct prognostic groups in lymphomas of both nodal and extranodal origin?

AIMS: Diffuse large B-cell lymphomas (DLBCL) can be divided into different subgroups (germinal center B-cell-like [GCB] and non-GCB) according to their gene expression profiles. Immunohistochemistry has been proposed as a surrogate for identifying these subgroups, but data about its efficacy in providing prognostic information are conflicting. METHODS AND RESULTS: This study retrospectively analyzed a series of 105 DLBCL, defined as GCB and non-GCB according to CD10, bcl-6, and MUM1 expression. All patients received a first-line anthracycline-based (CHOP-like) chemotherapy. A total of 50 patients (48%) were identified as GCB and 55 (52%) as non-GCB. The overall response rate was 89% (94/105), with 62 (59%) complete response. Disease progressions were equally distributed between the 2 subgroups and were not significantly different (P = .756) considering the primary site of involvement (nodal or extranodal). The median follow-up was 62 months (range 5-126 months). Overall survival at 5 years was not significantly different between the groups (P = .3468) and was 72.3% and 66.6% for GCB and non-GCB, respectively. CONCLUSION: The results do not support the prognostic value of GCB and non-GCB immunohistochemical categories in DLBCL of both nodal and extranodal origin. Furthermore, a limited number of antigens may be not sufficient to identify the same patterns defined by cDNA microarray. Prospective studies are warranted to address this issue.

Ten-year surveillance of nosocomial bloodstream infections: trends of aetiology and antimicrobial resistance in a comprehensive cancer centre.

BACKGROUND: Bloodstream infections (BSIs) are one of the major life-threatening infectious conditions in cancer patients and are responsible for prolonged hospital stays, high healthcare costs and significant mortality. Several clinical trials have reported an improved survival in patients treated with appropriate empirical broad-spectrum antibiotic therapy. Early detection of pathogens and determination of their susceptibility are essential for the optimization of treatment. Variability between hospitals is substantial and requires the individual analysis of local trends. The aim of this study is to assess the local epidemiology of BSI in a single cancer centre over a 10-year period. METHODS: Retrospective microbiological surveillance of all febrile/infective episodes occurring in oncological and surgical patients in a high-volume cancer centre between January 1999 and December 2008 were considered. Patients' data were collected, processed and analyzed using the epidemiological resource of the Virtuoso Plus software (Metafora Informatica Srl, Milano, Italy). Spearman's rank correlation coefficient, including the two-tailed test of significance, was used to investigate trends of incidence and rate of antibiotic resistance over the 10-year period. RESULTS: A total of 13,058 blood cultures (BCs) were performed in 2,976 patients. BCs were positive in 2,447 tests, representing 740 infective/febrile episodes: 358 (48%) in medical oncology and 382 (52%) in surgical wards. Gram-positives were responsible for the majority of episodes in oncological and surgical divisions (about 63% and 55%, respectively). Gram-positives were also the most common organism in non-catheter-related BSIs (CRBSIs) both in medical oncology (75%) and in surgical divisions (50%). Enterococci showed an increased resistance to levofloxacin, from 5.6% to 25.7% (p = 0.02) and to erythromycin, from 41.7% to 61.4%, (p = 0.05). Similarly, coagulase negative staphylococci (CoNS) developed resistance to levofloxacin and ciprofloxacin, passing from 33.9% to 67.4% (p = 0.01) and from 5.6% to 25.7% (p = 0.01), respectively. CONCLUSIONS: Gram-positives are the main pathogens of BSIs; there is no difference in aetiology of CRBSIs between surgical and oncological patients. The lower incidence of gram-positive non-CRBSIs in surgical patients was probably due to gram-negative infections secondary to surgical complications.

Expression of the human concentrative nucleotide transporter 1 (hCNT1) gene correlates with clinical response in patients affected by Waldenström's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) undergoing a combination treatment with 2-chloro-2'-deoxyadenosine (2-CdA) and Rituximab.

PURPOSE: Resistance to nucleoside analogues agents is likely to be multifactorial and could involve a number of mechanisms affecting drug penetration, metabolism and targeting. In vitro studies of resistant human cell lines have confirmed that human concentrative nucleoside transporter 1 (hCNT1)-deficient cells display resistance. EXPERIMENTAL DESIGN: We applied real-time PCR method to assess the mRNA expression of equilibrative and concentrative nucleoside transporter (hENT1, hCNT1), deoxycytidine and deoxyguanosine kinase (dCK, dGK), 5'-nucleotidase (5'-NT), ribonucleotide reductase catalytic and regulatory (RR1, RR2) subunits in bone marrow cells from 32 patients with Waldenström's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) who received 2CdA-based chemotherapy. Responses to chemotherapy, were then correlated to the expression of these markers. RESULTS: All 32 patients enrolled expressed lower levels of hCNT1 as compared to healthy donors. In univariate analysis, lower expression level of hCNT1 (p=0.0021) and RR2 (p=0.02) correlated with response to chemotherapy. In particular, patients with low levels of hCNT1 achieved inferior clinical response. No significant correlation between these genes expression and age, stage of disease was found. This study suggests that nucleotidase expression levels can be used to identify subgroups of WM and SLL patients who will likely respond differently to a 2CdA-based therapy.