Diagnosis and staging of small intestinal neuroendocrine tumors with CT enterography and PET with Gallium-68: preoperative risk stratification protocol.

PURPOSE: Pre-operative diagnosis and staging of small intestine neuroendocrine tumors (SI-NETs) remain sub-optimal, with open palpation during surgery still considered the gold standard. This limits a standardized implementation of minimally invasive surgery (MIS). The aim of this single-center retrospective study was to assess a tailored diagnostic work-up to identify candidates at low risk of undetected disease who may benefit from MIS. METHODS: Patients diagnosed with SI-NETs between 2013 and 2022 who underwent contrast-enhanced computed tomography enterography (CTE) and Ga68-DOTATOC-positron emission tomography-CT (68 Ga DOTATATE PET/CT) preoperatively and subsequently underwent open surgical resection were included. Imaging studies were reassessed by two radiologists. Combined use of CTE and 68 Ga DOTATATE PET/CT in determining primary lesion disease burden (number of lesions) and LN disease stage (distal and proximal relative to superior mesenteric vessels) was assessed, using surgical reports and pathology as gold standard. RESULTS: Overall, 56 patients were included. Sensitivity of CTE and 68 Ga DOTATATE PET/CT for at least one primary SI-NET was 100% and 94%, respectively. In the presence of concordance between studies, combined use of CTE and 68 Ga DOTATATE PET/CT for detection of single primary tumors improved specificity to 89% (n = 25/28) with a positive predictive value of 87.5% (n = 21/24). Distal LN disease was identified in 89.2% of cases (n = 33/37). The association of single lesion and distal LN disease was found pre-operatively in 32% of patients (n = 18). CONCLUSION: Combined use of CTE and 68 Ga DOTATATE PET/CT enables identifying low-risk surgical candidates (single SI-NET lesions with distal LN disease).

"Better late than never but never late is better", especially in young women. A multicenter Italian study on diagnostic delay for symptomatic endometriosis.

PURPOSE: The aim of the study was to assess the length of diagnostic delay of symptomatic endometriosis in Italy and analyse the presence of correlations between the socio-demographic status of patients and the clinical characteristics/type of diagnosis. MATERIALS AND METHODS: This multicenter cross-sectional questionnaire-based study was conducted in 10 tertiary Italian referral centres for diagnosis and treatment endometriosis. A total of 689 respondents with histologically proven endometriosis and onset of the disease with pain symptoms completed an on-line self-reported questionnaire written in their own language (World Endometriosis Research Foundation-Endometriosis Phenome and Biobanking Harmonisation Project-Endometriosis Patient Questionnaire-Minimum) evaluating endometriosis related symptoms, family history of endometriosis and chronic pelvic pain, demographic data, as well as medical, reproductive, and obstetric history. RESULTS: The mean diagnostic delay found was of 11.4 years. The mean time (14.8 years) from symptoms onset to diagnosis was significantly longer among patients aged 9-19 vs patients aged 20-30 (mean 6.9 years, p < 0.001) and patients aged 31-45 (mean 2.9, p < 0.001). No significant association were found between a delayed diagnosis and any of the clinically relevant factors such as the number or severity of the reported symptoms, familiarity, hormonal therapy intake or methodology of diagnosis. CONCLUSIONS: The mean diagnostic delay of endometriosis in Italy is about 11 years. The delay can be up to 4 years longer in patients with pain symptoms onset under 20 years. Educating clinicians and patients on pathologic nature of endometriosis related pelvic pain is advisable to reduce waiting time to diagnosis, especially for young women.

Anyplex II HPV test in detection and follow-up after surgical treatment of CIN2+ lesions.

Human papillomavirus (HPV) tests differ for technology, targets, and information on the genotype and viral load. In this study, we evaluated the performance of the Seegene Anyplex II HPV HR (Anyplex) assay in the detection of cervical intraepithelial lesions (CIN) and as a test-of-cure in the follow-up after surgical treatment. One hundred and sixty-seven women referred to the European Institute of Oncology, Milan, for surgical treatment of CIN2+ were enrolled. A cervical sample was taken before treatment and at the first follow-up visit: on these samples, Qiagen Hybrid Capture 2 (HC2), Roche Linear Array HPV Test (Linear Array), cytology and histology were performed at baseline, HC2, and cytology at follow-up. Anyplex genotyping HPV test was performed on a post aliquot from liquid-based cytology specimens when available. The concordance between Anyplex and HC2 was 93.6% at baseline and 76.7% at follow-up (3-9 months after treatment), respectively. The concordance between Anyplex and Linear Array was evaluable only at baseline (92.9%). No recurrence occurred in women without the persistence of the same genotype at follow-up. Seven women relapsed: six had persistence of the same genotypes (five HPV16, one HPV33, and one HPV39), while one tested negative not only with Anyplex but also with HC2 for the persistence of low-risk genotype infection (HPV73 only detected by Linear Array). Anyplex test represents a valid option for HPV detection and genotyping in order to stratify women at risk of high-grade lesions at baseline and to monitor patients treated for CIN2+ lesions during follow-up.

Local Failure After Accelerated Partial Breast Irradiation with Intraoperative Radiotherapy with Electrons: An Insight into Management and Outcome from an Italian Multicentric Study.

BACKGROUND: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. PATIENTS AND METHODS: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. RESULTS: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. CONCLUSIONS: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Feasibility and surgical impact of Z0011 trial criteria in a single-Institution practice.

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients.

Treatment of Chylothorax after Lung Resection: Indications, Timing, and Outcomes.

BACKGROUND: Chylothorax following pulmonary resection and lymphadenectomy for cancer is a potential severe complication in thoracic surgery. In the present study, we investigated the efficacy of the nonsurgical approach as well as the need for reoperation after conservative approach failure. METHODS: Chylothorax was diagnosed when chylous leakage from the chest drainage was observed and confirmed by the presence of triglycerides in the pleural fluid. We initially treated all the patients conservatively with complete oral intake cessation and total parenteral nutrition; if drainage output remained more than 800 mL/d after the first 5 days or major pleural effusion was observed at chest X-ray after chest tube removal, surgical treatment of chylothorax was indicated. RESULTS: Between January 1998 and December 2018, 5,072 patients underwent standard anatomical resection and mediastinal lymph node dissection for cancer at our institution. Among them, 30 patients (0.6%) developed chylothorax: 20 patients were effectively treated only by nil per os and low-fat diet, while 10 patients (33.3%) required surgical treatment. Mean age was 63 years; there were 24 male patients (80%); right-sided chylothorax was more frequent than left-sided chylothorax (22 vs. 8, respectively) although not statistically significant (p = 0.38); the only factor that seems to influence the need for reoperation is chylothorax flow rate during conservative treatment (p = 0.06). CONCLUSION: Conservative treatment is effective in the case of low flow-rate chylothorax (< 800 mL/d); in the case of a higher flow rate, surgical exploration is needed and thoracic duct ligation-with or without lymphatic sites clipping-provides definitive lymphostasis.

Distribution of High-Risk Human Papillomavirus Genotypes and Multiple Infections in Preneoplastic and Neoplastic Cervical Lesions of Unvaccinated Women: A Cross-sectional Study.

OBJECTIVE: The aim of the study was to investigate the distribution of high-risk (HR) human papillomavirus (HPV) genotypes and the role of multiple infection in preneoplastic and neoplastic cervical lesions, according to histology, age, and the number of genotypes per infection. MATERIALS AND METHODS: Nine hundred eighty-eight women affected by known HPV-related cervical lesions and attending the European Institute of Oncology, Milan, Italy, from December 2006 to December 2014, were selected for a cross-sectional study. Prevalence of HPV genotypes was calculated by histology and the number of genotypes per infection. Univariate and multivariable cervical intraepithelial neoplasia (CIN) 2-3 versus CIN 1 risks were estimated by logistic regression models. RESULTS: Overall, HPV 16 (53.1%), HPV 31 (15.1%), and HPV 58 (6.4%) were the most frequent genotypes in precancerous lesions. At multivariable analysis, HPV 16 (p = .02), 18 (p = .013), and 56 (p = .01) were significantly associated to worsen histology, whereas HPV 39 (p = .03) and 45 (p = .03) were statistically correlated only to the increasing number of genotypes per infections. Human papillomavirus 33 was the only genotype significantly related to both the number of genotypes per infection (p = .005) and age (p = .03). Infections by HR-HPV (odds ratio [OR] = 9.48, 95% CI = 3.77-23.8, p < .001), HPV genotypes covered by current vaccines (OR = 6.28, 95% CI = 4.05-9.75, p < .001), single HPV genotype (OR = 8.13, 95% CI = 4.12-16.0, p < .001), as well as age (OR = 1.13, 95% CI = 1.07-1.19, p < .001) were significantly associated to higher risk of CIN 2-3. CONCLUSIONS: The most of CIN 2+ lesions are sustained by HR-HPV genotypes, especially the ones covered by 9-valent vaccine; therefore, the widespread use of prophylactic HPV vaccines could significantly reduce the incidence of preneoplastic and neoplastic cervical lesions.

Metastatic and non-metastatic lymph nodes: quantification and different distribution of iodine uptake assessed by dual-energy CT.

OBJECTIVES: To evaluate quantification of iodine uptake in metastatic and non-metastatic lymph nodes (LNs) by dual-energy CT (DECT) and to assess if the distribution of iodine within LNs at DECT correlates with the pathological structure. METHODS: Ninety LNs from 37 patients (23 with lung and 14 with gynaecological malignancies) were retrospectively selected. Information of LNs sent for statistical analysis included Hounsfield units (HU) at different energy levels; decomposition material densities fat-iodine, iodine-fat, iodine-water, water-iodine. Statistical analysis included evaluation of interobserver variability, material decomposition densities and spatial HU distribution within LNs. RESULTS: Interobserver agreement was excellent. There was a significant difference in iodine-fat and iodine-water decompositions comparing metastatic and non-metastatic LNs (p < 0.001); fat-iodine and water-iodine did not show significant differences. HU distribution showed a significant gradient from centre to periphery within non-metastatic LNs that was significant up to 20-30% from the centre, whereas metastatic LNs showed a more homogeneous distribution of HU, with no significant gradient. CONCLUSIONS: DECT demonstrated a lower iodine uptake in metastatic compared to non-metastatic LNs. Moreover, the internal iodine distribution showed an evident gradient of iodine distribution from centre to periphery in non-metastatic LNs, and a more homogeneous distribution within metastatic LNs, which corresponded to the pathological structure. KEY POINTS: • This study demonstrated a lower iodine uptake in metastatic than non-metastatic LNs. • Internal distribution of HU was different between metastatic and non-metastatic lymph nodes. • The intranodal iodine distribution disclosed a remarkable correlation with the histological LN structure.

Evaluation of deep myometrial invasion in endometrial cancer patients: is dual-energy CT an option?

OBJECTIVES: Assessment of deep (>50%) myometrial invasion by dual-energy CT (DECT) and Trans-Vaginal US (TVUS) in patients with endometrial cancer. METHODS: We retrospectively enrolled patients with endometrial cancer who underwent DECT and TVUS for pre-surgical staging. Three sets of images were evaluated: 70 keV (routine CT images), 50 keV, and iodine-water reconstructions. The gold standard was pathology after surgery. The agreement between the different imaging modalities and the gold standard was estimated. Sensitivity, specificity and accuracy for each imaging modality were evaluated with 95% confidence intervals (CI). RESULTS: Thirty-nine patients were included. Median time from CT and TVUS to surgery was 23 and 18 days, respectively. The best agreement between evaluation of myometrial infiltration and the gold standard was 0.88 (0.72, 1.00) for the 50 keV images; the worst agreement was 0.43 (0.00, 0.88) for the 70 keV images. CT iodine reconstructions and US agreement were comparable. Specificity, sensitivity and accuracy were 0.91, 1.00, 0.94; 0.57, 0.86, 0.71; 0.82, 1.00, 0.87; 0.91, 0.77, 0.86 for 50 keV, 70 keV, iodine reconstructions and ultrasound, respectively. CONCLUSIONS: DECT is a promising tool for assessment of myometrial invasion in endometrial cancer patients, with a special focus on 50 keV images.

Resection of the Primary Tumor Followed by Peptide Receptor Radionuclide Therapy as Upfront Strategy for the Treatment of G1-G2 Pancreatic Neuroendocrine Tumors with Unresectable Liver Metastases.

BACKGROUND: A low burden of disease represents an independent favorable prognostic factor of response to peptide receptor radionuclide therapy (PRRT) in patients affected by gastro-entero-pancreatic neuroendocrine tumors. However, it is not clear whether this is due to a lower diffusion of the disease or thanks to debulking surgery. METHODS: From 1996 to 2013 those patients diagnosed with G1-G2 pancreatic neuroendocrine tumor (PNET) and synchronous liver metastases who were not deemed eligible for liver radical surgery but were eligible to receive upfront PRRT were prospectively included in the study. Two groups of comparison were identified: those submitted for primary tumor resection before PRRT and those who were not. The outcome was evaluated as: objective response to PRRT (OR), progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 94 subjects, 31 were previously submitted for primary tumor resection. After propensity score adjustments, patients who underwent surgery before PRRT showed higher stabilization or objective responses after PRRT (p = .006), and this translated into a better median PFS (70 vs. 30 months; p = .002) and OS (112 vs. 65 months; p = .011), for operated versus nonoperated patients, respectively. At multivariate analysis, operated patients showed a statistically significantly improved PFS: HR, 5.11 (95 % CI 1.43-18.3); p = .012, whereas Ki-67 in continuous fashion was correlated significantly with OS: 1.13 (95 % CI 1-1.27); p = .048. CONCLUSIONS: Primary tumor resection prior to PRRT can be safely proposed in G1-G2 PNETs with diffuse liver metastases because it seems to enhance response to PRRT and to improve significantly PFS.

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors.

PURPOSE: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. METHODS: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples. RESULTS: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. CONCLUSION: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.

Ultrasonographic diagnosis and longitudinal follow-up of recurrences after conservative surgery for borderline ovarian tumors.

BACKGROUND: Borderline ovarian tumors are generally diagnosed in young women. Because of the young age of patients at first diagnosis and at recurrence, and given the good prognosis of borderline ovarian tumors, a conservative surgical approach in those women who wish to preserve their fertility is advised. In this scenario, transvaginal ultrasound examination plays a key role in the detection of borderline ovarian tumor recurrence, and in assessment of amount of normal functioning parenchyma remaining. To date, no data are available about the natural history of borderline ovarian tumor recurrence. OBJECTIVE: The aim of the study was to determine growth rate of recurrent ovarian cysts by a scheduled follow-up by ultrasound examination, in women previously treated with fertility-sparing surgery due to borderline ovarian tumors. STUDY DESIGN: In this prospective observational study, we collected data from 34 patients previously treated with fertility-sparing surgery due to borderline ovarian tumors, who had a suspicious recurrent lesion. The patients underwent transvaginal ultrasonographic examination every 3 months, until the clinical setting recommended proceeding with surgery. According to cyst size at study entry, they were categorized into 3 groups: ≤10 mm, 10-20 mm, and >20 mm. Summary statistics for cyst size, growth rate, and the probability of remaining within the same dimension category at first ultrasound during the follow-up were also obtained. For each cyst the growth rate was calculated as the slope of the linear interpolation between 2 consecutive measurements. RESULTS: Follow-up timing (P < .001), cyst size (P < .001), and micropapillary pattern (P < .001) were factors significantly affecting the cyst growth both in univariate and multivariate analysis. According to size category at first ultrasound, growth rate ranges from a minimum of 0.06 mm/mo for cysts <10 mm up to 1.92 mm/mo for cysts >20 mm. The final histology of all recurrent lesions confirmed the same histotype of primary borderline ovarian tumors. CONCLUSION: This article represents the first observational study that describes the trend in the growth rate of borderline ovarian tumor recurrence in relation to their size detected at the first ultrasound examination. The findings of this study seem to confirm, in selected patients, that a thorough ultrasonographic follow-up of borderline ovarian tumor recurrence has proven to be safe and feasible. The final goal of such management is to maximize the impact on fertility potential of these young women without worsening their prognosis.

Chest wall resection and reconstruction for locally recurrent breast cancer: From technical aspects to biological assessment.

INTRODUCTION: Breast cancer is the leading cause of cancer death among women in the industrialized countries. The incidence of local recurrences after mastectomy and breast-conserving therapy varies between 5% and 40% depending on risk factors and primary therapy. METHODS: From April 1999 to April 2011, 40 patients underwent chest wall resection and reconstruction for locally recurrent breast carcinoma with chest wall invasion. The main goal of surgery was local disease control to palliate clinical symptoms. RESULTS: Local radical resection was achieved in 26 patients (65%). One, 2 and 5 year overall survival rates were 94.4%, 82.0% and 68.5%; 1, 2 and 5 year disease-free survival rates were 94.4%, 73.6% and 45.5% respectively. Univariate analysis indicated age (p = 0.002) and synchronous distant metastases (p = 0.020) as factors having a negative impact on overall survival; multivariate analysis disclosed age (p = 0.052) and synchronous metastases (p = 0.059) as factors with a slight negative impact on overall survival. Older age was associated with improved overall survival. Univariate analysis indicated synchronous distant metastases (p = 0.029) and the need of post resectional additional treatments (p = 0.022) as factors adversely conditioning disease-free survival or time to progression; multivariate analysis disclosed the need of post resectional additional treatments (p = 0.036) as the only factor adversely conditioning disease-free survival or time to progression. CONCLUSIONS: Chest wall resection and reconstruction for locally recurrent breast cancer is a feasible and safe procedure providing adequate local disease control and an excellent palliation of very disabling symptoms in a selected group of patients.

Chlorambucil-rituximab as first-line therapy in patients affected by follicular non-Hodgkin's lymphoma: a retrospective single-centre study.

Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, has been shown to be active in newly diagnosed and relapsed patients with follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. Many studies suggest that the prognosis of patients with FL may improve when it is used in combination with chemotherapy. Despite these advances, the disease remains essentially incurable with standard therapy, and novel approaches to treatment are needed because optimal therapy is not defined. The combination of chlorambucil-rituximab is one of several standard treatment options for FL. Here, we considered data arising from 75 patients with newly diagnosed FL at the European Institute of Oncology treated with the combination of rituximab plus chlorambucil. The aim of this study was to evaluate the efficacy and safety of chlorambucil and rituximab, delivered 6 mg/m(2) /day orally for 6 weeks and 375 mg/m(2) in a standard 4-weekly schedule, respectively. Patients responding to the induction therapy received a prolonged therapy with four additional cycles of chlorambucil plus rituximab. Seventy-one patients (94.6%) completed the treatment; four patients discontinued treatment because of grade 3-4 hematological toxicity. The overall response rate was 97.3% including 74.7% of complete responses. Only two patients had a stable disease at revaluation after treatment. With a median follow-up of 57 months, 72 patients (96%) are alive. Median event-free survival (EFS) and median overall survival (OS) were not reached; 5-year OS rate was 98.4%. The 5-year EFS was 71.3%. By univariate and multivariate analyses, elevated beta-2 microglobulin levels and partial responses to therapy were correlated with worse EFS. These results suggest that the combination of chlorambucil and rituximab is an active and safe regimen in patients with newly diagnosed FL, principally in those with low tumour burden and favourable prognostic factors.

PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker.

Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with increased gene dosage for PMP22. Therapeutic approaches are currently aiming at correcting PMP22 over-expression. It is unknown whether PMP22 can be used as a biological marker of disease progression and therapy efficacy. We performed quantitative real-time polymerase chain reaction on skin biopsies of 45 patients with CMT1A, obtained at study entry and after 24-months of treatment either with ascorbic acid or placebo. Data of a subgroup of patients were also compared with matched healthy subjects. Finally, we analysed PMP22 messenger RNA levels in sural nerve biopsies. We did not find significant differences in the levels of any known PMP22 transcripts in treated or untreated patients with CMT1A, thus confirming that ascorbic acid does not impact on the molecular features of CMT1A. Most importantly, we did not observe any correlation between PMP22 messenger RNA levels and the different clinical and electrophysiological outcome measures, underscoring the weakness of PMP22 to mirror the phenotypic variability of patients with CMT1A. We did not find increased PMP22 messenger RNA levels in skin and sural nerve biopsies of patients with CMT1A compared with relative controls. In conclusion, this study shows that ascorbic acid does not impact on PMP22 transcriptional regulation and PMP22 is not a suitable biomarker for CMT1A.

Cost effectiveness of different central venous approaches for port placement and use in adult oncology patients: evidence from a randomized three-arm trial.

BACKGROUND: No randomized trials have so far investigated the cost effectiveness of different methods for implantation and use of central venous ports in oncology patients. PATIENTS AND METHODS: Overall, 403 patients eligible for receiving intravenous chemotherapy for solid tumours were randomly assigned to implantation of a single type of port, either through a percutaneous landmark access to the internal jugular vein, an ultrasound (US)-guided access to the subclavian vein, or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Insertion and maintenance costs were estimated by obtaining the charges for an average implant and use, while the costs of the management of complications were analytically assessed. The total cost was defined as the purchase cost plus the insertion cost plus the maintenance cost plus the cost of treatment of the complications, if any. RESULTS: A total of 401 patients were evaluable-132 with the internal jugular vein, 136 with the subclavian vein and 133 with the cephalic vein access. No differences were found for the rate of early complications. The US-guided subclavian insertion site had significantly lower failures. Infections occurred in 1, 3, and 3 patients (internal jugular, subclavian, and cephalic access, respectively; p = 0.464), whereas venous thrombosis was observed in 15, 8, and 11 patients, respectively (p = 0.272). Mean cost for purchase, implantation, diagnosis and treatment of complications in each patient was 2,167.85 for subclavian US-guided, 2,335.87 for cephalic, and 2,384.10 for internal jugular access, respectively (p = 0.0001). CONCLUSION: US real-time guidance to the subclavian vein resulted in the most cost-effective method of central venous port placement and use.

Efficacy of 9°Yttrium-ibritumomab tiuxetan in relapsed/refractory extranodal marginal-zone lymphoma.

We evaluated clinical activity of 9°Yttrium-ibritumomab (9°Y-ibritumomab) tiuxetan in extranodal marginal-zone lymphoma. From May 2004 to April 2011, 30 patients affected by relapsed/refractory marginal-zone lymphoma--arisen at any extranodal site--received 9°Y-ibritumomab tiuxetan at the activity of 0.4 mCi/kg. Median age was 57 years. At time of treatment, 13 out of 30 patients had disseminated disease (stage III/IV). All patients had received a previous treatment with a maximum of 7. Overall response rate was 90%: 23 patients achieved a complete response (77%); partial response occurred in 4 patients (13%), stable disease in 2 patients (7%) and 1 progression (3%). With a median follow-up of 5.3 years, median time to relapse was not reached; 2 patients relapsed after complete response; 18 out of 23 complete responses are still responders after >3 years, 12 of them after >5 years. 9°Y-ibritumomab tiuxetan seems to be active in patients with extranodal marginal-zone lymphoma relapsed/refractory to conventional treatment including radiotherapy. These results suggest that radioimmunotherapy could represent a possible option for the treatment in this subset of patients.

Pain and small fiber function in Charcot-Marie-Tooth disease type 1A.

INTRODUCTION: Charcot-Marie-Tooth (CMT) disease type 1A is the most common form of CMT. The main clinical features are distal weakness, sensory loss, and skeletal deformities. Although pain is a frequent complaint, small fiber involvement in CMT1A has not been studied extensively. METHODS: We assessed pain and small fiber involvement in 49 CMT1A patients using a variety of pain scales, pain questionnaires, and thermal thresholds. RESULTS: Forty-three of 49 patients (88%) complained of pain. The pain was localized to the feet in 61% of patients. Only 18% of patients had neuropathic pain. Cold and warm detection thresholds were elevated in 53% and 12% of patients, respectively. CONCLUSIONS: Our findings confirm that CMT1A patients have significant pain, which is more likely to be multifactorial in origin and suggests that a proportion of patients have small fiber dysfunction affecting mainly thinly myelinated Aδ fibers.

Recovery and time to growth of isolates in blood culture bottles: comparison of BD Bactec Plus Aerobic/F and BD Bactec Plus Anaerobic/F bottles.

BACKGROUND: This study was done to compare the growth of pathogens in paired aerobic/anaerobic blood culture bottles versus the use of only aerobic bottles, and to analyze the time to growth in both atmospheres. METHODS: We retrospectively evaluated the results of all blood cultures collected over a 2-y period for the diagnosis of central venous catheter-related bloodstream infections or other severe infections in oncology patients. RESULTS: Among the 487 isolates, 174 (35.7%), all aerobic, grew only in the aerobic bottle; 250 (51.3%), all aerobic, grew in both bottles; and 63 (12.9%) grew only in the anaerobic bottle, of which 24 were anaerobic and 39 were aerobic microorganisms (8% of positive blood cultures). Of these 39 aerobic microorganisms, 12 were Gram-negative, 17 staphylococci (4 were Staphylococcus aureus), 5 streptococci, 2 Gram-positive bacilli, and 3 mixed growth. Though the mean time to positivity of pathogens grown in both atmospheres was significantly lower in the aerobic bottle than in the anaerobic bottle, in 71 cases (28.4%) the pathogens developed earlier in the anaerobic bottle than in the aerobic bottle - in 36 of these cases at least 1 h earlier, which is significant for starting targeted therapy. CONCLUSIONS: The use of paired aerobic/anaerobic blood culture bottles allowed the diagnosis of a percentage of bacteraemia due to either anaerobic or aerobic pathogens that would have been missed, as they grew only in the anaerobic atmosphere. Moreover in 8% of bacteraemia we identified a significant decrease in the time to detection, resulting in the opportunity to better manage the infections without an increase in costs.

The Impact of pelvimetry on anastomotic leakage in a consecutive series of open, laparoscopic and robotic low anterior resections with total mesorectal excision for rectal cancer. .

BACKGROUND/AIMS: Recently, pelvic anatomy has been taken into consideration and related to surgical outcome indicators after low anterior resection (LAR). Several pelvimetric parameters have been matched with conversion rate, postoperative complications and duration of surgery in laparoscopic series, and with the quality of specimen and pathologic outcomes in further open surgical series. METHODOLOGY: In 97 consecutive patients submitted to sphincter-saving LAR with total mesorectal excision (TME) five pelvic dimensions were measured by abdominal computed tomography scan: anteroposterior and transverse diameters in the pelvic inlet (IAP and ITRA), anteroposterior and transverse diameters in the pelvic outlet (OAP and OTRA), and the pelvic depth. The endpoint evaluated was anastomotic leakage (AL) rate. RESULTS: There were 51 open, 12 laparoscopic and 34 robotic LARs. The sum of IAP OAP and OTRA (Pelvic Index) significantly predicted AL showing that starting from the cut-point of 290 mm down to a PI of 278 mm the odds-ratio of having an AL increased from 2.63 (95% CI: 1.10,5.47) to 5.07 (95% CI: 1.35,8.02). CONCLUSIONS: The sum of the 3 pelvic dimensions which we termed "Pelvic Index" was associated to AL following sphinctersaving LAR. This may be considered in planning the surgical strategy for rectal cancer patients.