Realising the European network of biodosimetry: RENEB-status quo.

Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed.

Post-chemoradiation anastomotic recurrence in locally advanced rectal cancer: no increased risk associated with distal margin.

BACKGROUND AND PURPOSE: Anastomotic recurrence after radical sphincter-preserving surgery preceded by neoadjuvant therapy in locally advanced rectal cancer is an uncommon event that merits further assessment. The aim of this study is to analyze the effect of preoperative chemoradiation on the risk of anastomotic recurrence. Based on the initial extension of the tumor, we analyzed whether the distal surgical section was calculated through the virtual initial extension of the rectal tumor. PATIENTS AND METHODS: Eligible patients with locally advanced rectal cancer were offered preoperative chemoradiation, sphincter sparing surgery and intraoperative radiation therapy boost. RESULTS: 180 patients were treated with anterior resection (40 %), low anterior resection (45.6 %) and ultra-low anterior resection (14.4 %). With a median follow-up of 41.1 months (0.36-143 months), anastomotic recurrence was diagnosed in 9 patients (5 %). There was no statistical correlation with downstaging (T or N), downsizing effects, or with distance from the lower limit of the residual lesion to the distal margin. Virtual intratumoral surgical section was speculated in 44 patients (3 developed anastomotic recurrence; 6.8 vs 4.8 %, p = 0.482). CONCLUSION: Anastomotic recurrence in patients with rectal cancer treated with neoadjuvant chemoradiation is an infrequent event. Virtual intratumoral surgical sections followed by anastomosis do not contribute to an excessive risk of recurrence. Our findings encourage the development of policies for preservation of the ano-rectal complex in rectal cancer patients.

Intraoperative radiotherapy with electrons: fundamentals, results, and innovation.

RATIONALE AND OBJECTIVES: To analyse the programme activity and clinical innovation and/or technology developed over a period of 17 years with regard to the introduction and the use of intraoperative radiotherapy (IORT) as a therapeutic component in a medical-surgical multidisciplinary cancer hospital. MATERIAL AND METHODS: To standardise and record this procedure, the Radiation Oncology service has an institutional programme and protocols that must be completed by the different specialists involved. For 17 years, IORT procedures were recorded on a specific database that includes 23 variables with information recorded on institutional protocols. As part of the development and innovation activity, two technological tools were implemented (RADIANCE and MEDTING) in line with the standardisation of this modality in clinical practice. RESULTS: During the 17 years studied, 1,004 patients were treated through 1,036 IORT procedures. The state of the disease at the time of IORT was 77% primary and 23% recurrent. The origin and distribution of cancers were 62% gastrointestinal, 18% sarcomas, 5% pancreatic, 2% paediatric, 3% breast, 7% less common locations, and 2% others. The research and development projects have generated a patent on virtual planning (RADIANCE) and proof of concept to explore as a professional social network (MEDTING). During 2012, there were 69 IORT procedures. There was defined treatment volume (target or target region) in all of them, and 43 were conducted by the virtual planning RADIANCE system. Eighteen have been registered on the platform MEDTING as clinical cases. CONCLUSION: The IORT programme, developed in a university hospital with an academic tradition, and interdisciplinary surgical oncology, is a feasible care initiative, able to generate the necessary intense clinical activity for tending to the cancer patient. Moreover, it is a competitive source for research, development, and scientific innovation.

Research opportunities in intraoperative radiation therapy: the next decade 2013-2023.

The reality of intraoperative radiation therapy (IORT) practice is consistent with an efficient and highly precise radiation therapy technique to safely boost areas at risk for local recurrence. Long-term clinical experience has shown that IORT-containing multi-modality regimens appear to improve local disease control, if not survival in many diseases. Research with IORT is a multidisciplinary scenario that covers knowledge from radiation beam adapted development to advance molecular biology for bio-predictability of outcome. The technical parameters employed in IORT procedures are important information to be recorded for quality assurance and clinical results analysis. In addition, specific treatment planning systems for IORT procedures are available, to help in the treatment decision-making process. A systematic revision of opportunities for research and innovation in IORT is reported including radiation beam modulation, delivery, dosimetry and planning; infrastructure and treatment factors; experimental and clinical radiobiology; clinical trials, innovation and translational research development.

Realising the European Network of Biodosimetry (RENEB).

In Europe, a network for biological dosimetry has been created to strengthen the emergency preparedness and response capabilities in case of a large-scale nuclear accident or radiological emergency. Through the RENEB (Realising the European Network of Biodosimetry) project, 23 experienced laboratories from 16 European countries will establish a sustainable network for rapid, comprehensive and standardised biodosimetry provision that would be urgently required in an emergency situation on European ground. The foundation of the network is formed by five main pillars: (1) the ad hoc operational basis, (2) a basis of future developments, (3) an effective quality-management system, (4) arrangements to guarantee long-term sustainability and (5) awareness of the existence of RENEB. RENEB will thus provide a mechanism for quick, efficient and reliable support within the European radiation emergency management. The scientific basis of RENEB will concurrently contribute to increased safety in the field of radiation protection.

[Change of treatment in patients with multiple sclerosis and its consequences in clinical practice]. / Cambio de tratamiento en pacientes con esclerosis multiple y sus consecuencias en la practica clinica.

INTRODUCTION: Thirty per cent of patients with multiple sclerosis (MS) present a suboptimal response to treatment in the first few years. The real impact of the change of treatment has still not been well established. AIMS: To describe our clinical practice with regard to the change of treatment in MS patients with a suboptimal response and to analyse their progress depending on our therapeutic decisions. PATIENTS AND METHODS: The study is observation-based and retrospective. The sample was made up of patients with relapsing-remitting MS and at least one event after establishing immunomodulatory treatment. Both the intention to change treatment and the delays until the actual change took place were taken into account. The theoretical consequences of these strategies were measured by the changes in the expected curve of the Multiple Sclerosis Severity Scale (MSSS). RESULTS: A comparison of those who changed immunomodulator with those that did not showed that 64.3% versus 35.3%, respectively, improved on the expected curve of the MSSS (p > 0.05). Patients who improved the expected curve of the MSSS had changed treatment before those who did not improve (1.9 months versus 6 months), although the differences were not significant. The mean time that elapsed between taking the decision to change and actually changing the treatment was 2.70 ± 3.55 months. CONCLUSIONS: Despite limitations due to the size of the sample, the patients with a suboptimal response who changed treatment early could benefit from an improvement in their expected progression on the MSSS.

[Refractive surprise after LASIK]. / Sorpresa refractiva tras LASIK.

CASE REPORT: A female patient underwent laser in situ keratomileusis (LASIK) in both eyes. The final degree of astigmatism in her left eye was double the preoperative value due to an error in data management. Complex surgery to both eyes was necessary to resolve the mistake. DISCUSSION: Complications in refractive surgery can occur, however errors in data management must be minimized by double-checking. Solutions to resolve the errors made can be difficult and the entire staff must share responsibility to avoid these undesirable outcomes.

Pathologic downstaging of T3-4Nx rectal cancer after chemoradiation: 5-fluorouracil vs. Tegafur.

PURPOSE: To describe downstaging effects in locally advanced rectal cancer induced by 2 fluopirimidine radiosensitizing agents given through different routes in conjunction with preoperative radiotherapy. METHODS AND MATERIALS: From March 1995 to December 1999, two consecutive groups of patients with cT3-4Nx rectal cancer (94% CT scan, 71% endorectal ultrasound) were treated with either (1) 45-50 Gy (1.8 Gy/day, 25 fractions) and 5-fluorouracil (5-FU) (500-1,000 mg/m2 by 24-h continuous i.v. infusion on Days 1-4 and 21-25) or (2) oral Tegafur (1,200 mg/day on Days 1-35, including weekends). Surgery was performed 4 to 6 weeks after the completion of chemoradiation. RESULTS: The total T downstaging rate was 46% in the 5-FU group and 53% in the Tegafur group. Subcategories were downstaged by the sensitizing agents (5-FU vs. Tegafur) as follows: pT0-1, 14% vs. 23%; pT2, 32% vs. 32%; pT3, 49% vs. 37%; pT4, 5% vs. 7%; and N(0), 74% vs. 86%. Analysis of residual malignant disease in the specimen discriminated mic/mac subgroups (mic: <20% of microscopic cancer residue), with evident superior downstaging effects in the Tegafur-treated group: pTmic 23% vs. 58% (p = 0.002). CONCLUSIONS: When administered concurrent with pelvic irradiation, oral Tegafur induced downstaging rates in both T and N categories superior to those induced by intermediate doses of 5-FU by continuous i.v. infusion. In this pilot experience, oral Tegafur reproduced the characteristics of downstaging described previously when full doses of 5-FU have been combined with radiotherapy.

Gamma-detecting probe used intraoperatively to locate the sentinel lymph node in patients with malignant melanoma.

OBJECTIVE: To assess the usefulness of lymphoscintigraphy and intraoperative gamma probe in the detection of sentinel lymph nodes. DESIGN: Prospective open study. SETTING: University hospital, Spain. SUBJECTS: 40 patients with malignant melanoma (24 stage I/II, 16 stage III). INTERVENTION: The day before operation a lymphoscintigram with 99mTc-nanocolloid was taken and the first lymph node identified was considered to be the sentinel node. A hand-held gamma probe was used for intraoperative mapping. MAIN OUTCOME MEASURE: Identification of the sentinel node. RESULTS: Sentinel nodes were identified in 39/40 patients (98%). In 24 patients with stage I/II disease, 34 sentinel nodes were found (6 invaded and 28 clear of melanoma). A total number of 161 regional lymph nodes were harvested, none of them invaded by melanoma. In 16 patients with stage III disease, 22 sentinel nodes were located (14 invaded and 8 clear of melanoma). A total of 89 regional lymph nodes were excised in patients with invaded sentinel nodes (44 of which were invaded and 45 clear of disease). 41 lymph nodes were excised from patients with clear sentinel nodes, and all were also clear of melanoma. CONCLUSIONS: We conclude that this is a useful technique for the selection of patients with melanoma who may require lymphadenectomy.

Conformationally restricted PACAP27 analogues incorporating type II/II' IBTM beta-turn mimetics. Synthesis, NMR structure determination, and binding affinity.

To probe the importance of a proposed beta-turn within residues S9-R12 of PACAP for recognition by VIP/PACAP receptors, compounds 1 and 2, two conformationally restricted analogues of PACAP27 incorporating respectively (S)- or (R)-IBTM as type II or II' beta-turn dipeptide mimetic at the Y10-S11 position, were synthesized. According to 1H NMR conformational analyses in aqueous solution and 30% TFE, both PACAP27 and the [S-IBTM(10,11)]PACAP27 analogue 1 adopt similar ordered structures. PACAP27 shows an N-terminal disordered region (residues H1-F6) and an alpha-helical conformation within segment T7-L27. For residues S9-R12, our data seem more compatible with a segment of the alpha-helix than with the beta-turn previously proposed for this fragment. In compound 1 the alpha-helix, also spanning T7-L27 residues, appears slightly distorted at the N-terminus relative to the native peptide. Although this distortion could lead to the marked decrease in binding affinity of this compound at the VIP/PACAP receptors, the lack of the Y10 side chain in analogues 1 and 2 could also significantly affect the binding of these compounds.

99mTc-MIBI scintimammography as a complement of the mammography in patients with suspected breast cancer. A multicentre experience.

The aim of this work has been to evaluate the clinical usefulness of 99mTc-MIBI scintimammography, used as a complement to mammography, in the study of patients with suspected breast cancer. We performed prone breast scintigraphy in 253 patients (268 lesions) with suspected breast cancer. The size and degree of the suspected breast cancer was evaluated by mammography. Diagnosis was established by biopsy. Malignancy was diagnosed in 155 lesions and benign diseases in 113. The results of the scintimammography were a sensitivity of 91%, a specificity of 71%, PPV=81% and NPV=85%. In lesions smaller than 1 cm, sensitivity and specificity were 57% and 100%; in lesions with a diameter of between 1 and 2 cm, these figures were 90% and 72% respectively, and in lesions of more than 2 cm the sensitivity was 99% and the specificity 50%. On mammography, 155 lesions were considered as having a high suspicion of malignancy, whilst 72 were indeterminate and 41 had a low probability. In lesions with a low or indeterminate suspicion of malignancy on mammography, the sensitivity and NPV of the scintimammography were 97% and 98%. Scintimammography is a useful technique in the study of lesions where breast cancer is suspected. Scintimammography results are closely related to tumour size and the degree of mammographic suspicion. Scintimammography can be useful where mammography identifies lesions with a low or indeterminate suspicion of malignancy.

[Treatment of metastatic bone pain with repeated doses of strontium-89 in patients with prostate neoplasm]. / Tratamiento del dolor óseo metastásico con dosis repetidas de Estroncio-89 en pacientes con neoplasia de próstata.

This study has aimed to evaluate the usefulness of repeated treatment with 89Sr in patients with prostate neoplasm and metastatic bone pain. Seventeen patients with partial or complete response after the first dose were retreated with two or more doses (total of 39 doses). The Karnofsky functional status, pain and degree of analgesia were assessed. After the first dose the response was good in 68% of the patients and partial in 32%. After the second dose, the response was good in 62% of the patients, partial in 15% and there was no response in 23% of the cases. The pre-treatment Karnofsky functional status and duration of the effect of 89Sr was lower after the second dose (p = 0.03, p = 0.02), but there were no statistically significant differences in the type of response. In conclusion, re-treatment with 89Sr can be administered safely and with a similar response to that achieved after the first dose.

Optimization of technetium-99m-HMPAO leukocyte scintigraphy in evaluation of active inflammatory bowel disease.

Although [99mTc]HMPAO-labeled leukocyte scintigraphy is widely used in the assessment of IBD, the time point chosen for imaging is still controversial. The aim of the present study was to determine the optimal scanning sequence to assess IBD extension and activity. Sixty-two consecutive patients with active and 18 with inactive IBD were prospectively studied. Clinical evaluation, colonoscopy, radiology, and scintigraphy were performed within three days, without changes in the patient's treatment. Compared to early scan (45 min), late scan (3 hr) had a higher sensitivity (85% vs 100%) and accuracy (85% vs 95%) in identifying patients with active IBD and in defining IBD extension. Combinations of values from both scans did not improve accuracy of scintigraphy, which is lower in Crohn's disease than in ulcerative colitis and also in patients receiving steroid treatment. In conclusion, a single late scintigraphy scan provides the best means to identify patients with active IBD and to assess disease extension.

In-111 octreotide scan in a case of a neuroendocrine tumor of unknown origin.

Major neuroendocrine tumors contain many somatostatin receptors. This feature allows for the localization of primary tumors and tumor metastases by scintigraphy with the radiolabeled somatostatin analog octreotide. We describe a patient with nonspecific clinical data and ultrasonography and CT that showed an isolated focal lesion in the liver. In-111 octreotide scintigraphy was essential in establishing the diagnosis of liver metastasis from a neuroendocrine tumor confirmed by pathologic findings. Because clinical symptoms recurred, ultrasonography and CT were performed a few months after surgery. Both were negative. However, In-111 octreotide scintigraphy suggested multiple bone metastases and established the diagnosis of bone metastases from a neuroendocrine tumor, which was confirmed by Tc-99m MDP bone scans and MRI.

Quantitative evaluation of bone scintigraphy in the assessment of Paget's disease activity.

Interest in the assessment of activity of Paget's disease has increased since the advent of effective therapies. The aim of this study was to develop a quantitative method for the scintigraphic assessment of Paget's disease activity in bone. Twenty patients with Paget's disease were studied prospectively. A scintigraphic visual activity index, together with a quantitative activity index that reflects both the extent and activity of the disease, was obtained for each patient. The quantitative activity index is calculated as the sum of the activity (geometric mean measured from the anterior and posterior views) for all affected bones divided by a reference obtained in non-affected bone. To evaluate the validity of the scintigraphic methods, several biochemical markers of bone turnover were assessed: serum total alkaline phosphatase and serum propeptide aminoterminal of type I procollagen (PINP) as markers of bone formation; urinary hydroxyproline and urinary N-terminal cross-linked telopeptide of type I collagen (NTx) as markers of bone resorption. The visual and quantitative scintigraphic indices were highly correlated (r = 0.78, P < 0.0001). The highest correlations between the biochemical markers and the quantitative activity index were found for PINP (r = 0.69, P < 0.001), which was the most sensitive marker of bone formation, and for urinary NTx (r = 0.63, P < 0.005), which was the most sensitive marker of bone resorption. In conclusion, quantitative evaluation of bone scintigraphy allows easy and objective assessment of Paget's disease activity and it may be useful in evaluating the effectiveness of therapies.

[Sentinel lymph node detection with lymphoscintigraphy and intraoperative probe in malignant melanoma patients]. / Detección del ganglio centinela mediante linfogammagrafía y sonda detectora intraoperatoria en pacientes con melanoma maligno.

BACKGROUND: The sentinel lymph node is the first node in a lymphatic basin to receive lymphatic drainage from a tumor site. If this node is free of tumor, then radical lymphadenectomy may be avoided. The goal of this study was to assess the usefulness of lymphoscintigraphy and intraoperative gamma probe in the sentinel node detection in patients with malignant melanoma. METHOD: We prospectively studied 40 patients with malignant melanoma (24 in I/II stages and 16 in III stage). The day before surgery a lymphoscintigraphy with 99mTc-nanocolloid was performed and the first lymph node identified was considered as sentinel node. For intra-operative mapping a hand-held gamma probe was used. RESULTS: Sentinel nodes were identified in 39/40 (97.5%) patients. In 24 patients with I/II stages 34 sentinel nodes were demonstrated (six positive and 28 negative for malignant melanoma). A total amount of 161 regional lymph nodes was harvested, all of them being negative for malignant melanoma. In 16 patients with III stage, 22 sentinel nodes were located (14 positive and eight negative for malignant melanoma). A total of 89 regional lymph nodes were excised in sentinel nodes positive patients (44 positive and 45 negative for malignant melanoma) and 36 lymph nodes in sentinel node negative, all of them negative for malignant melanoma. CONCLUSIONS: In patients with malignant melanoma, lymphoscintigraphy with 99Tc-nanocolloid is useful for the detection of sentinel lymph node. Biopsy of this node is useful for the selection of patients to undertake a lymphadenectomy.

Bacteremia caused by digestive system endoscopy.

AIM: to evaluate bacteremias caused during endoscopic examination of the digestive tract. PATIENTS AND METHODS: prospective study of randomly selected patients who underwent digestive system endoscopic examination. Emergency endoscopic examinations were excluded. RESULTS: a total of 102 patients were analyzed. Of 44 patients who underwent gastroscopy, 11 (25%) subsequently had positive blood culture, and Staphylococcus spp and Streptococcus spp were isolated. Of 30 patients who underwent colonoscopy, 3 (10%) had positive blood cultures, and Staphylococcus spp were isolated. Of 28 patients who underwent endoscopic retrograde cholangiopancreatography, 11 (39.2%) had positive blood cultures, and Escherichia coli, Morganella morganii, Staphylococcus spp and Streptococcus spp were isolated. No deaths, endocarditis or other septic phenomena were attributed to bacteremia. CONCLUSIONS: the incidence of bacteremia ranged from 10% to 39% depending on the type of endoscopy. The microorganisms that were isolated most frequently were Staphylococcus spp and Streptococcus spp. Gram-negative bacilli and enterobacteria were isolated in patients who had undergone endoscopic retrograde cholangiopancreatography.

Radioimmunoguided surgery of colorectal carcinoma with an 111In-labelled anti-TAG72 monoclonal antibody.

Radioimmunoscintigraphy (RIS) and radioimmunoguided surgery (RIGS) were assessed for their usefulness in patients with colorectal carcinoma. Twenty-nine patients (18 primary tumours, 10 with a suspicion of recurrence and one colonic diverticulitis) were studied. Radioimmunoscintigraphy was performed 48 and 72 h after the injection of an anti-TAG72 monoclonal antibody (CYT-103) labelled with 111In. Radioimmunoguided surgery was performed between 72 and 96 h post-injection. During surgery, a systematic screening was performed with a hand-held gamma detecting probe and a surgical index (tumour-to-normal tissue) was obtained. There were statistically significant differences between counts in normal tissue versus tumour (P < 0.001) and RIGS was considered positive for the detection of tumour if the ratio between the counts in the area suspicious of tumour and the counts in the normal tissue was greater than 1.5. The overall sensitivity for RIS and RIGS was 71.4% (55.6% in primary tumours and 100% in recurrences) and 82.1% (83.3% in primary tumours and 80% in recurrences), respectively. Radioimmunoguided surgery changed the surgical procedure in two cases with small tumour deposits. Occult regional lymph node involvement in primary tumours was not found; therefore, RIGS, as a complementary technique to RIS, is particularly useful in recurrences and can help the surgeon in the resection of small tumour deposits which are difficult to localize.