Antonio Castagnoli

Long-term ambulatory enterogastric reflux monitoring. Validation of a new fiberoptic technique.

A new technique for the long-term ambulatory detection of enterogastric and nonacid gastroesophageal reflux has been conceived, developed, and validated. It is based on the use of a fiberoptic sensor that utilizes the optical properties of bile.In vitro studies have shown good precision, good stability, sensitivity of 2.5 μmol/liter bilirubin concentration, as well as a useful working range of 2.5–100 μmol/liter bilirubin concentration.In vivo studies have been performed in 29 subjects. Simultaneous gastric aspirations have allowed a comparison of fiberoptic system measurements both with spectrophotometric analysis and bile acid concentrations of corresponding gastric juice samples. Linear correlations were shown between fiberoptic assessment and both spectrophotometric and bile acid concentration findings (P<0.01). Simultaneous assessment of reflux with the fiberoptic system and cholescintigraphy has shown a 92.9% concordance as regards the presence or absence of reflux. Present results imply that the fiberoptic system is an important tool for the understanding of the clinical relevance of enterogastric and nonacid gastroesophageal reflux.

Positron emission tomography in the staging of patients with Hodgkin's lymphoma. A prospective multicentric study by the Intergruppo Italiano Linfomi.

In this prospective multicentric study, we investigated the contribution of positron emission tomography (PET) scanning to the staging of Hodgkin’s lymphoma (HL) by computed tomography (CT) and attempted to determine whether it has any impact on therapeutic approach. One hundred eighty six consecutive patients with HL from six Italian centers were enrolled in this study. They were staged with conventional methods; 2-[fluorine-18]fluoro-2-deoxy-d-glucose PET scanning were prospectively compared to CT. CT and FDG-PET stages were concordant in 156 patients (84%) and discordant in 30 patients (16%). PET stage in comparison to CT stage was higher in 27 patients (14%) and lower in 3 patients (1%). The programmed treatment strategy was modified in 11 out of 30 patients (37%) after the definition of final stage. If we considered the 123 CT staged patients with localized stage, ten patients (8%) with a change of stage from localized to advanced after PET evaluation were treated with different strategy. FDG-PET was shown to be a relevant, non-invasive method that supplements conventional procedures and should therefore be used routinely to stage HL, particularly in early stage patients, where a change in stage may modify disease management.

Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.

PURPOSE The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. PATIENTS AND METHODS The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. RESULTS In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physicians decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. CONCLUSION Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup.

The prognostic value of positron emission tomography performed after two courses (INTERIM-PET) of standard therapy on treatment outcome in early stage Hodgkin lymphoma: A multicentric study by the fondazione italiana linfomi (FIL)

This retrospective study included 246 patients with a new diagnosis of Hodgkin Lymphoma (HL) with a localized‐stage (IA‐IIA), consecutively admitted from January 2002 to December 2008, by twelve Italian hematological centers on behalf of Fondazione Italiana Linfomi (FIL).

Serum amylase and tissue polypeptide antigen as biochemical indicators of salivary gland injury during iodine-131 therapy

The study evaluated the possibility of using serum α-amylase and tissue polypeptide antigen (TPA) as biochemical markers of radiation injury in the salivary gland of patients with thyroid carcinoma treated with iodine-131. The results demonstrated that the two molecules increased 1 day after 1311 administration and returned to near control values on the 3rd day. The increase was greater and longer lasting in those patients treated with the higher 1311 administered activity. However, when the patients were divided into groups based on recovery time, which determined patients with different radionuclide elimination rates, the increase in the two molecules was greater and more lasting in those subjects with a longer period of hospitalization. A comparison with the values obtained from patients with tumours of the head and neck treated with external radiotherapy demonstrated that after the 1st day of treatment the salivary gland received an absorbed dose which, based on α-amylase levels, ranged between 0.24 and 1.89 Gy and, based on TPA levels, between 0.28 and 2.29 Gy.

Octreoscan SPET Evaluation in the Diagnosis of Pancreas Neuroendocrine Tumors

The study describes the results of Octreoscan SPET (OCTSPET) qualitative and semi-quantitative evaluation in 38 patients with suspected pancreatic neuroendocrine tumors. SPET studies were acquired at 4 and 24 hours after the injection of 111-220 MBq of 111-In-pentetreotide (Octreoscan). Qualitative and semi-quantitative evaluations were performed. The semi-quantitative approach was based on the time course of Tumor/Non Tumor ratios (TNTinc) from 4 and 24 hours. The OCTSPET results were true positive in 18 of 19 patients (10 gastrinoma, 5 insulinoma, 1 neuroendocrine tumor, 1 glucagonoma and 1 carcinoid) and false negative in one insulinoma. Besides, 20 of 38 patients (52%) had clinical plans modified after OCTSPET; OCTSPET was the only positive diagnostic test in 14 of 19 patients (73%) and guided the surgery decision in 14 of 25 patients (56%). In conclusion, these data indicate that Octreoscan represents an excellent tool for the diagnosis of pancreatic neuroendocrine tumors.

The new FDG brain revolution: the neurovascular unit and the default network

F-fluorodeox-yglucose (FDG), it was possible to see and study the livingbrain in humans! Pioneers were top experts who provideddifferent specialized expertise, but strictly cooperatingbetween themselves [1]. Physicists, engineers and mathe-maticians were actively involved in producing the besthardware and software. The research on crystals, inidentifying the most effective electronics, in definingaccurate methods for attenuation and scatter correctionand so on, was nevertheless limited by the relatively poortechnology, with the main consideration being limitedcomputer power. These developments stimulated a majorinterest in the brain. Satisfactory sensitivity and resolution,together with reliable solutions to the technical problems,were only achieved with dedicated cerebral PET scannerswhich had a field of view that permitted exclusive analysisof the brain.Basic scientists had the possibility of realizing ascientific dream: the transfer of data on cerebral glucosemetabolism acquired in animals by quantitative autoradi-ography to humans. Another issue in the original FDG PETresearch was to consider mandatory absolute quantification.Thus arterial (or arterialized) sampling, to obtain data to beincluded in mathematical models, was routinely performed.However, because the equations included nonmeasurableparameters, the presence of a lumped constant affectedabsolute measurement in an individual [2–4]. PET teamsincluded (and were directed by) clinical experts includingnot only nuclear physicians, but also other professionalssuch as neuroradiologists, neurologists and psychiatrists,who frequently cooperated with psychologists, anatomistsand physiologists.Because of the unsatisfactory spatial resolution and thenegative influence of the partial volume effect, inpresence of glucose uptake in the normal brain, only alow lesion/background ratio was achievable, except forhot spots, i.e. the presence of focal areas of increaseduptake determined by physiological and/or pathologicalcauses. Therefore, the use of FDG as a positive indicatorwasrestrictedinthefirststudiesandinthesearchforhotspots, many studies involved physiological stimulationtests (closed/open eyes, auditory system, etc.) in normalsubjects [5, 6]. Similarly, major interest in pathologicalanalysis was directed to the evaluation of brain tumours,starting from Warburg’s hypothesis of higher FDG uptakein malignant lesions with respect to benign ones [7]. Withfurther clinical experience, in the analysis of patients withepilepsy, a higher sensitivity was clearly demonstratedduring the ictal phase, the focus being seen as a hot spot,with respect to the interictal period when the lesion wasnot easily detectable, being an area with a slightly reducedoverall FDG uptake [8, 9]. Discrepant results in epilepsyclearly demonstrate how, in the absence of a structurallesion evident on CT, it is more difficult to search for afunctional alteration when it corresponds to an area ofdecreased uptake (cold spot).

PET scan evaluation of thymic mass after autologous peripheral blood stem-cell transplantation in an adult with non-Hodgkin's lymphoma

We report the case of a 31-year-old man with anaplastic large-cell lymphoma successfully treated with chemotherapy who showed mediastinal widening 5 months after autologous stem-cell transplantation. CT scan and PET evaluations were consistent with the diagnosis of benign thymic hyperplasia. Because of the rapid and aggressive course of this type of lymphoma, and the progressive widening of the mass at CT scan, we performed a mediastinal biopsy that confirmed these findings, showing normal thymic tissue. This is the first case of benign thymic hyperplasia defined with FDG-PET and confirmed by histologic evaluation.

Quantitative comparison between 99mTc-HMPAO and 99mTc-ECD: measurement of arterial input and brain retention

This report describes a comparative study between technetium-99m ethyl cysteinate dimer (ECD) and 99mTc-hexamethylpropylene amine oxime (HMPAO) in five neurological patients. The conversion kinetics of the tracers in the blood from forms capable of diffusion across the blood-brain barrier to non-diffusible forms were studied by arterial sampling and rapid octanol extraction. We observed that HMPAO has a faster conversion rate in the blood but that the fraction of the injected dose available for brain extraction is higher than in the case of ECD. Regional brain concentrations of the tracers were measured with single-photon emission tomography (SPET) 35 min and 60 min after the injection and remained stable within this interval. On the basis of the measurements of the arterial input and of SPET brain concentrations of the tracers, the regional steadystate influx constants (Ki in ml/min/g) were determined for several brain regions. In the grey matter the Ki values were (mean ± SD) 0.32 ± 0.03 and 0.35 ± 0.04 for HMPAO and ECD, respectively; in the white matter the values were 0.23 ± 0.01 and 0.23 ± 0.02, respectively. The Ki values of the two tracers in corresponding regions were closely correlated (P<0.001). The correspondence of the Ki values of ECD and HMPAO demonstrates that ECD can also be considered a tracer that may be used for quantitative measurements of brain perfusion.

Radioisotopic lymphatic mapping of the sentinel node in melanoma: importance of immunohistochemistry.

Background Elective lymph node dissection (ELND) for patients with malignant melanoma is still controversial. A possible alternative could be biopsy of the first tumor draining lymph node, the sentinel node (SN), which can be identified by means of radionuclide techniques. Aim Our study was undertaken to assess the accuracy of lymph node biopsy and to stress the importance of immunohistochemistry (IHC) in the pathological assessment of the SN for improved staging of the primary tumor. Methods We performed lymphoscintigraphy (LS) in 183 melanoma patients (89 with melanoma of the legs, 11 of the arms and 83 of the trunk). Our protocol consisted of preoperative peritumoral i.d. injection of 99mTc-labeled microcolloid to define the regional lymphatic basin and identify the sentinel node by means of planar scintigraphy. In 147 of the 183 cases a gamma probe (GP) was used during surgery to trace the SN. Vital blue dye was used during surgery in all cases. The SNs were excised for pathological examination. The pathological status of the SN was defined by means of examination of frozen sections, hematoxylin-eosin staining and immunohistochemistry for S-100 and HMB-45 MAb. Results At least one separate focus of activity was identified by LS in 182 out of 183 patients; in all 147 cases where a GP was used, it was successful in tracing the SN. LS with cutaneous mapping of the SN successfully guided the surgical excision in 177 of the 183 cases; in the 7 remaining cases, i.e. 7 out of 83 cases with SNs in the axillary basin, GP was not used and no elective node dissection was performed. Metastases were found in 39 of these 177 cases. In all 39 cases the SNs were the only positive nodes in the basin. Of the 39 metastases 18 were identified by means of frozen section, 12 by means of hematoxylin-eosin, and 9 by means of immunohistochemistry. We therefore emphasize the importance of immunohistochemistry in the pathology of LS for improved staging of the primary tumor.