Multimodal imaging with <Superscript>18</Superscript>F-FDG-PET/CT and <Superscript>111</Superscript>In-Octreotide SPECT in patients with metastatic medullary thyroid carcinoma

Objective

The aim of our study was to determine the role of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and indium-111 Octreotide single photon emission tomography (¹¹¹In-Octreotide SPECT) in the evaluation of metastatic medullary thyroid carcinoma (MMTC).

Methods

Twenty-five MMTC patients were retrospectively evaluated. All patients had undergone whole-body ¹⁸F-FDG-PET/CT including 20 who had also undergone ¹¹¹In-Octreotide SPECT within a maximum interval of 6 weeks. Diagnostic contrast-enhanced computed tomography (CT) alone or as part of ¹⁸F-FDG-PET/CT examination was performed in all patients.

Results

Contrast-enhanced CT detected a total of 131 lesions including 79 enlarged lymph nodes and 14 bone lesions. ¹⁸F-FDG-PET/CT visualized a total of 92 true positive lesions (SUV_max range 1.1–10.0, mean 4.0 ± 1.7) including 66 lymph nodes, 7 of which were not enlarged on CT, and 8 bone metastases. In the 20 patients studied with both techniques, a total of 64 and 46 true positive lesions were detected by ¹⁸F-FDG-PET/CT and ¹¹¹In-Octreotide SPECT, respectively. In particular, ¹⁸F-FDG uptake was found in 43 lymph nodes and in 7 bone metastases whereas ¹¹¹In-Octreotide uptake was detected in 27 lymph nodes and in 10 bone metastases.

Conclusions

In MMTC patients, ¹⁸F-FDG-PET/CT provides a useful contribution mainly in evaluating lymph node involvement whereas ¹¹¹In-Octreotide SPECT can contribute to the detection and somatostatin receptor characterization especially of bone lesions.

     

A pharmacokinetic-based test to prevent severe 5-fluorouracil toxicity

BACKGROUND AND OBJECTIVES: Dihydropyrimidine dehydrogenase (DPD) plays a key role in the catabolism of 5-fluorouracil (5-FU) to 5-fluoro-5,6-dihydrouracil (5-FDHU), and as such, an impairment of DPD has been recognized as an important factor for altered 5-FU and 5-FDHU pharmacokinetics, predisposing patients to the development of severe 5-FU-associated toxicity. Our objectives were to avoid severe 5-FU toxicities in patients with greatly impaired 5-FU and 5-FDHU pharmacokinetics after the administration of a reduced test dose of 5-FU and to investigate possible 5-FU or 5-FDHU pharmacokinetic parameters of the test dose related to the most common drug toxicities that affect patients after the first cycle of 5-FU chemotherapy. METHODS: Pharmacokinetics of 5-FU/5-FDHU and DPD activity in peripheral blood mononuclear cells (PBMCs) were examined in 188 gastrointestinal cancer patients given a test dose of 5-FU, 250 mg/m2, 2 weeks before starting the planned 5-FU treatment of 370 mg/m2 plus l-folinic acid, 100 mg/m2, for 5 days every 4 weeks. Drug levels were examined by HPLC, and toxicities were graded according to World Health Organization criteria. RESULTS: The 5-FU test dose was well tolerated in all patients. Of 188 patients, 3 (1.6%) had marked alterations of 5-FU/5-FDHU pharmacokinetics (ie, 5-FU half-life [t(1/2 beta)] >5 hours, 5-FU total body clearance [CL(TB)] <1 L x h(-1) x m(-2), and 5-FDHU time to reach maximum plasma concentration [t max] > or = 45 minutes); they were excluded from 5-FU treatments and treated with irinotecan, which was well tolerated. The plasma disposition of 5-FU in the remaining 185 patients revealed an area under the curve (AUC) of 3.73 +/- 2.18 h x microg/mL (mean +/- SD), maximum plasma concentration (Cmax) of 16.78 +/- 8.61 microg/mL, and t(1/2 beta) of 0.16 +/- 0.15 hour, whereas the CL(TB) was 65.67 +/- 31.86 L x h(-1) x m(-2). The 5-FDHU plasma profile showed a Cmax value of 3.64 +/- 1.94 microg/mL, whereas the t max value was 26.63 +/- 10.06 minutes, with an AUC value of 3.71 +/- 1.90 h x microg/mL. The PBMC DPD activity was 202.15 +/- 141.14 pmol 5-FDHU x min(-1) x mg(-1) protein (95% confidence interval, 165-239.3 pmol 5-FDHU x min(-1) x mg(-1) protein). A significant correlation between 5-FU AUC and 5-FDHU AUC was found (r = 0.5492, P < .0001), whereas a weaker correlation between PBMC DPD activity and both 5-FDHU AUC (r = 0.328, P = .0121) and 5-FDHU Cmax (r = 0.369, P = .0044) was found. Interestingly, no relationships between PBMC DPD activity and common toxicities were found, whereas 5-FDHU t max values greater than 30 minutes were associated with the risk of moderate to severe neutropenia and diarrhea (P = .0323 and P = .0138, respectively; chi-square test). CONCLUSIONS: This study suggests a successful approach for preventing severe or life-threatening toxicities in gastrointestinal cancer patients who are candidates for standard 5-FU treatment by analyzing the 5-FU and 5-FDHU pharmacokinetic parameters after the administration of a reduced 5-FU test dose.     

Posttransplant hematopoiesis in patients undergoing sibling allogeneic stem cell transplantation reflects that of their respective donors although with a lower functional capability

We tested the principle of whether patient long-term hematopoiesis following allogeneic stem cell transplantation (allo-SCT) reflects the characteristics of the hematopoiesis of their respective donor. For this purpose, we analyzed bone marrow (BM) hematopoiesis using long-term cultures (LTC), delta assays, and clonogeneic assays as well as CD34+ cells and their subsets by flow cytometry in a series of 37 patients undergoing allo-SCT, and we compared it to that of their respective human leukocyte antigen-matched sibling donors in a paired study performed more than 1 year after the transplant procedure. Interestingly, the main factor that influenced post-allo-SCT BM hematopoiesis in the long term was donor hematopoiesis. Nevertheless, compared to their respective donors, patients exhibited a significantly lower number of colony-forming units granulomonocytic, burst-forming units erythroid, and immature progenitors (CD34++/CD38dim/CD90+/CD133+ cells, LTC-initiating cells, and colonies generated in the delta assay). Moreover, BM stromal function was diminished in patients undergoing allo-SCT compared to their donors. In addition, the presence of chronic graft-versus-host disease under immunosuppressive treatment also conditioned an impaired hematopoietic function. In summary, our study shows that BM hematopoiesis evaluated more than 1 year after an allo-SCT mainly reproduces that of their respective donors, although with a significantly decreased in vitro activity.     

Non-invasive evaluation with continuous Doppler of the systolic pressure of the right ventricle in patients with tricuspid insufficiency

Tricuspid regurgitation (TR) is detected by Doppler echocardiography in a high proportion of patients with right ventricle pressure or volume overload. Continuous wave Doppler (CW) provides a noninvasive estimation of the transtricuspid systolic pressure gradient, applying the modified Bernoulli formula to the maximum velocity of the TR jet. The purpose of this study was to test the accuracy of the CW prediction of systolic right ventricular pressure (RVPs), obtained adding a clinical estimate of the mean right atrial pressure (RAPm) to the Doppler derived pressure gradient. The study population consisted of 22 adult patients with Doppler proved TR, undergoing right heart catheterization (cath) for mitral valve disease (12 pts), atrial septal defect (8 pts), dilated cardiomyopathy (1 pt) or pulmonary hypertension (1 pt). Two studies were duplicated after nifedipine administration. TR was graded by pulsed Doppler flow mapping as mild in 7, moderate in 11, severe in 4 pts. RAPm was estimated clinically from the inspection of neck veins pulsatility (mmHg = pulsatility cm+5/1.3). At CATH RVPs ranged from 27 to 80 (46 +/- 17) mmHg, RAPm from 0 to 13 (6 +/- 3) mmHg. RVPs Doppler prediction showed a close correlation with CATH (r .97, SEE 4.2 mmHg), with a slight mean underestimation (-2 +/- 4 mmHg) (Fig. 3, Tab. I). The discrepancies between CW and CATH ranged from -9 to +10 mmHg, almost entirely due to inaccuracy of the RAPm clinical estimate (r .48, see 3.8 mmHg) (Fig. 4, Tab. I).(ABSTRACT TRUNCATED AT 250 WORDS)     

Liver Transplantation for Recurrent Hepatocellular Carcinoma on Cirrhosis After Liver Resection: University of Bologna Experience

Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy.
From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence.
According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS).
Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively.
LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure.     

Molecular and epidemiological characteristics of blood-borne virus infections among recent immigrants in Spain

The increased immigration from developing regions to Western countries raises public health concerns related to blood-borne viruses. The prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic virus (HTLV) infections among recent immigrants attending several Spanish diagnostic centers in years 2002 and 2003 was examined. Genetic characterization of viral subtypes and its relationship with distinct at-risk populations was carried out. A total of 1,303 immigrants were identified. They originated in Latin America (46.9%), Sub-Saharan Africa (23.7%), Eastern Europe (9.4%), and the Maghreb (9.2%). Seroprevalence rates were as follows: HIV-1 4.2%, HBV 4.1%, HCV 2.9%, and HTLV-1 0.8%. All patients with HIV-1 non-B subtypes, HBV genotypes E and A3, and HCV genotype 4 were sub-Saharan Africans, and had been infected mainly through heterosexual contacts. In contrast, Latin American homo/bisexual men carried HIV-1 subtype B most likely acquired after their arrival to Spain. In conclusion, while Sub-Saharan Africans carry wide diverse genetic variants of blood-borne viruses, the absence of high-risk practices in most cases could limit the spread of these variants. In contrast, Latin Americans with high-risk sexual practices may be a particularly vulnerable collective to acquire blood-borne viruses in the receptor country.     

Surgical versus non-surgical endodontic re-treatment for periradicular lesions

Background : Though success rates of endodontic initial treatment have been improving over the years, persistence of periapical disease is far from being a rare condition. The most common therapeutical options for the re‐treatment of teeth with periapical pathosis are non‐surgical orthograde treatment and surgical treatment. Selection between alternative treatments should be based on assessment of respective benefits (mainly healing) and risks from studies consistent with a high level of evidence. Objectives : To test the null hypothesis of no difference in outcome between surgical and non‐surgical therapy for endodontic re‐treatment of periradicular lesions. Search strategy : The Cochrane Oral Health Group Trials Register, CENTRAL, MEDLINE and EMBASE were searched with appropriate search strategies. Handsearching included eight dental journals. The bibliographies of relevant clinical trials and relevant articles were checked for identifying studies outside the handsearched journals. Seven manufacturers of instruments in the field of endodontics or endodontic surgery or both, as well as the authors of the identified randomized controlled trials (RCTs) were contacted in order to identify unpublished or ongoing RCTs. No language restriction was placed. The last electronic search was conducted on 3rd April 2007. Selection criteria : All RCTs about re‐treatment of teeth with periapical pathosis in which both surgical and non‐surgical approaches were used and having a follow up of at least 1 year were considered for the analysis. Data collection and analysis : A quality assessment of the included RCTs was carried out and the authors were contacted for missing information. We independently extracted the data in duplicate. We followed the Cochrane Oral Health Group's statistical guidelines. Main results : Three RCTs were identified, two of them reporting different data from the same clinical study. The risk of bias was judged as moderate for one study and high for the other one. One hundred and twenty‐six cases were followed up for at least 1 year, and 82 had a follow up of 4 years. At the 1‐year follow up the success rate for surgical treatment was slightly better than non‐surgical (risk ratio (RR) 1.13; 95% confidence interval (CI) 0.98 to 1.30). When the follow up was extended to 4 years (only one RCT made it) the outcome for the two procedures became similar. Authors' conclusions : The finding that healing rates can be higher for cases treated surgically as compared to those treated non‐surgically, at least in the short term, is based on two RCTs only. A single RCT reported that in the medium to long term healing rates for the two procedures are very similar. There is currently scarce evidence for a sound decision making process among alternative treatments for the re‐treatment of a periradicular pathosis. More well‐designed RCTs should be performed with follow up of at least 4 years, and with a consistent sample size, to detect a true difference in the long term between the outcomes of the two alternative treatments, if any exist.     

Advances in diagnosis and therapy of neuroendocrine tumors

Neuroendocrine tumors represent a group of neoplasias characterized by significant histopathologic and biological heterogeneity. Diagnosis of neuroendocrine tumors relies upon histological examination augmented by newer techniques such as position emission tomography, meta-iodobenzylguanidine scintigraphy or octreoscan. Surgery represents the definite and curative therapeutic approach in early phase tumors. In metastatic or advanced disease, medical treatment is the best choice. Somatostatin analogs allow adequate control of the carcinoid syndrome, without a significant effect on tumor cell growth. Interferon-alpha may represent an alternative, alone or in association with somatostatin analogs. Chemotherapy is the best choice in the treatment of neuroendocrine tumors characterized by a poor differentiation grade and a high proliferation rate.     

Experimental rabies: ultrastructural quantitative analysis of the changes in the sciatic nerve

To study the pathology of peripheral nerves in experimental rabies infection, street rabies virus ws inoculated into the right footpad of two groups of mice, A and B, which received, respectively, 10(4.5) LD50 and 10(3.5) LD50 of the virus. Paralysis was observed in 60% of animals of group A and 20% of group B. The main ultrastructural abnormality present in the sciatic nerves was degeneration of about 40% of myelinated axons. Only occasional unmyelinated axons were degenerated. Figures were similar for nerves of either side and for both groups. Frequency histograms of axonal diameter showed axons of all sizes to be altered in group A, whereas in group B there was tendency for larger axons to be damaged. Electron microscopy showed no typical bullet-shaped viral particles. Asymptomatic animals which received the higher dose of the inoculum showed a small (less than 1%) percentage of necrotic myelinated axons.