Beam and installation improvements of the NIO1 ion source.

The NIO1 (Negative Ion Optimization phase 1) source can provide continuous beam operation, which is convenient for systematic parameter and equipment studies. Even in the pure volume production regime, the source yield was found to depend on conditioning procedures. Magnetic configuration tests continued adding magnets to the existing setup; the filter field component Bx has been progressively extended to span the -12 to 5 mT range, and as a trend, source performances improved with |Bx|. The progress of camera beam diagnostics and of the quality of the volume-produced H- beam is also shown. The status, off-line results, and reliability of a first NIO1 cesium oven are discussed; other upgrades in preparation (cavity ring down spectrometer, the end calorimeter, and conceptual tests of the energy recovery system) are also listed.

Diffuse malignant peritoneal mesothelioma: Failure analysis following cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC).

Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The issue of treatment failure has never been extensively addressed. The present study assessed the failure pattern, management, and outcome of progressive DMPM following comprehensive treatment. Clinical data on 70 patients with DMPM undergoing cytoreduction and HIPEC were prospectively collected; after a median follow-up of 43 months, disease progression occurred in 38 patients. Progressive disease distribution in 13 abdominopelvic regions was analyzed. In 28 patients undergoing adequate cytoreduction (residual tumor < or =2.5 mm), clinicopathological factors correlating to disease progression in each region were investigated. Median time to progression was 9 months [95% confidence interval (CI) 1.6-35.9]. Median survival from progression was 8 months (95% CI 4-16.2). The failure pattern was categorized as peritoneal progression (n = 31), liver metastases (n = 1), abdominal lymph-node involvement (n = 2), pleural seeding (n = 4). Small bowel was the single site most commonly involved (n = 27). Residual tumor < or =2.5 mm (versus no visible) was the only independent risk factor for disease progression in epigastric region (P = 0.047), upper ileum (P = 0.029), upper jejunum (P = 0.034), and lower jejunum (P = 0.002). Progressive disease was treated with second HIPEC in 3 patients, debulking in 4, systemic chemotherapy in 16, and supportive care in 15. At multivariate analysis, time to progression <9 months (P = 0.009), poor performance status (P = 0.005), and supportive care (P = 0.003) correlated to reduced survival from progression. We conclude that minimal residual disease, compared with macroscopically complete cytoreduction, correlated to failure in critical anatomical areas, suggesting the need for maximal cytoreductive surgical efforts. In selected patients, aggressive management of progressive disease seems worthwhile.

Multicystic peritoneal mesothelioma treated by surgical cytoreduction and hyperthermic intra-peritoneal chemotherapy (HIPEC).

BACKGROUND: Multicystic peritoneal mesothelioma (MPM) is an extremely uncommon lesion with uncertain malignant potential. Multiple recurrences after surgical interventions and transition to aggressive malignancies have been reported. Here, we review our experience with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of MPM. PATIENTS AND METHODS: Five women with MPM underwent 6 procedures of cytoreduction and close-abdomen HIPEC with cisplatin and doxorubicin. Three patients had recurrent disease after 1, 2 and 4 previous debulkings, respectively. RESULTS: Optimal cytoreduction (residual tumor nodules < or =2.5 mm) was performed in all the procedures. One grade 4 postoperative complication (NCI/CTCAE v.3.0) and no operative mortality occurred. Median follow-up was 31 months (range 3-102). MPM recurred in two patients: one is presently disease-free after a second cytoreduction with HIPEC and the other is alive with minimal stable disease. CONCLUSION: Definitive eradication by means of cytoreduction and HIPEC seems a safe and effective therapeutic option for MPM.

[Updated treatment of peritoneal carcinomas: a review]. / Trattamento innovativo delle neoplasie peritoneali.Una review.

Peritoneal surface malignancy (PSM) is a clinical entity with an unfavourable prognosis, which characterizes the evolution of neoplastic diseases from the abdominal and/or pelvic organs and could also be the terminal stage of extra-abdominal tumors. Examples of diseases that can spread mainly within the peritoneal cavity are appendiceal tumors, ovarian cancer, colorectal cancer, abdominal sarcomatosis, gastric cancer and peritoneal mesothelioma. The locoregional therapy is defined as the combination of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). The rationale of this combined therapy for PSM is based on the natural history of this clinical entity that remains confined in the peritoneal cavity for most of its natural history. This pattern of spread would seem to indicate the potential usefulness of selectively increasing drug concentration in the tumour-bearing area by direct intraperitoneal chemotherapy instillation. This approach led to these outcomes: the median survival of colorectal carcinoma and ovarian cancer was 32 months; patients with peritoneal mesothelioma showed 57% survival at 5 years, while in patients with appendiceal mucinous tumors and pseudomyxoma peritonei (PMP) the 10 years overall survival was 78%. A significant improvement in survival was associated with hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients with gastric cancer. Considering the constant increasing of diseases treatable with this procedure, more centres should be activated. The establishment of a clear policy and scientific guidelines is mandatory, in order to perform the CRS+HIPEC safely, minimizing treatment-related morbidity and mortality and maximizing the results in terms of survival and quality of life.

Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: The experience of National Cancer Institute of Milan.

AIMS: We report the effects of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) in the treatment of advanced/recurrent epithelial ovarian cancer (EOC) on survival, morbidity and mortality. PATIENTS: Forty EOC patients were studied. Median age was 52.5 years (range: 30-68) and median follow-up 26.1 months (range: 0.3-117.6). Most patients presented advanced disease (stage III/IV). Previous systemic chemotherapy included cisplatin-based, taxol-based or taxol/platinum containing regimens. RESULTS: After the CRS, 33 patients presented no macroscopic residual disease. Five-year overall survival was 15%; the mean overall and progression-free survivals were 41.4 and 23.9 months, respectively. The morbidity, toxicity and mortality rates were 5%, 15% and 0%, respectively. CONCLUSION: Our results suggest that CRS + IPHP merits further evaluation by a formal prospective trial.

First experiments with the negative ion source NIO1.

Neutral Beam Injectors (NBIs), which need to be strongly optimized in the perspective of DEMO reactor, request a thorough understanding of the negative ion source used and of the multi-beamlet optics. A relatively compact radio frequency (rf) ion source, named NIO1 (Negative Ion Optimization 1), with 9 beam apertures for a total H(-) current of 130 mA, 60 kV acceleration voltage, was installed at Consorzio RFX, including a high voltage deck and an X-ray shield, to provide a test bench for source optimizations for activities in support to the ITER NBI test facility. NIO1 status and plasma experiments both with air and with hydrogen as filling gas are described. Transition from a weak plasma to an inductively coupled plasma is clearly evident for the former gas and may be triggered by rising the rf power (over 0.5 kW) at low pressure (equal or below 2 Pa). Transition in hydrogen plasma requires more rf power (over 1.5 kW).

Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer.

Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC). However most of the studies testing the combined approach are observational and have been conducted in inhomogeneous series so that the evidence supporting the performance of this combined treatment is still poor. Median Overall and Disease Free Survivals of up to 64 months and 57 months, respectively have been reported. Although a rate of morbidity of up to 40% has been observed in some series the CRS + HIPEC continues to gain an increased popularity. Several prospective randomized trials are ongoing using the procedure in various time points of the disease. In this review several issues such as the impact of cytoreduction and residual disease (RD) on outcomes as well as the role of HIPEC will be updated from the literature evidence. Some controversial points HIPEC related will also be discussed. Recent experiences regarding the introduction of a more aggressive surgical approach to upper abdomen to resect peritoneal carcinomatosis (PC) allowed increased rates of optimal cytoreduction and has demonstrated an apparent better outcome. This evidence associated with the positive results phase III trial testing normothermic intraperitoneal as first-line chemotherapy is guiding some investigators to propose the CRS + HIPEC in the primary setting. Several prospective phase II and III trials have recently been launched to validate the role of the combined treatment in various time points of disease natural evolution.

Cost analysis of the combined procedure of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

AIM: The aim of the present study was to address the economic cost of the innovative comprehensive approach involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat peritoneal surface malignancies, and to compare it with the financial support received by our centre. METHODS: A retrospective economic analysis was carried out on 382 consecutive procedures performed at a tertiary referral centre during the period 1995-2008. The costs of the combined therapy were estimated using the activity-based costing methodology. The financial support was assessed according to the current diagnosis-related group classification and reimbursement rates. RESULTS: The mean cost for one hospital stay was euro36,015.89 (range 28,435.24-82,189.08); mean length of stay was 24.3 days (range 9-108). In counterpart, our hospital received a total financial support of euro804,483.30, resulting in a deficit of euro1861,301.99 for the two years. CONCLUSION: The Italian current diagnosis-related groups classification does not include cytoreduction and HIPEC. This results in a relevant economic deficit for the hospitals offering this treatment option to their patients and a slow diffusion of the technique in our country. Two corrective measures are needed: to include this procedure in the official list of medical acts, and to determine its specific cost for reimbursing.

Multicystic and well-differentiated papillary peritoneal mesothelioma treated by surgical cytoreduction and hyperthermic intra-peritoneal chemotherapy (HIPEC).

BACKGROUND: Multicystic peritoneal mesothelioma (MPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM) are exceedingly uncommon lesions with uncertain malignant potential and no uniform treatment strategy. The aim of the current study was to review our experience with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in these clinical settings. METHODS: Four women with MPM and eight with WDPPM underwent 13 procedures of cytoreduction and close-abdomen HIPEC with cis-platin and doxorubicin. Seven patients had recurrent disease after previous debulking (one operation in five patients, two in one, four in one). Potential clinicopathological prognostic factors were assessed. RESULTS: Optimal cytoreduction (residual tumor nodules