The paleoradiology importance in the study of relics: the unique densitometric analysis of a bone relic of Saint Nicholas.

INTRODUCTION: DXA have greatly contributed to the development of paleoradiology, a branch of diagnostic imaging that allows to obtain information about human remains in contexts of archaeological and/or forensic interest. In this manuscript we report the unique experience of DXA performed on the relic of a Saint; in particular we analyzed a skeletal fragment of St. Nicholas, kept in the Basilica of Bari (Italy) since 1087. MATERIALS AND METHODS: The bone to be examined consisted of the posterior arch of the ninth left rib that was 12cm long, 1.2cm maximum width and 1.7cm thick at the body. The data acquired from the densitometric study were performed using the anthropometric measures reported in historical records of St. Nicholas' life: sex (male), age (75 years), weight (70kg), height (167cm), and ethnicity (Caucasian). In addition to the examination of the relic, a comparison assessment was made with the rib of a healthy 60 years old man (height of 170cm, without known skeletal pathologies). This sample had a length of 19cm, maximum width at the head 1cm, and 0.7cm thick at the body. The analysis of bone fragments is different from the analysis of bones in the context of the human body (where soft tissues are placed around the skeleton); for this reason, one of the most critical issues was to create a support that would allow the analysis of bone fragments. We simulated conditions similar to those occurring in patients: a density scale was established, using a specific plexiglass phantom on which the bone fragments to be examined were placed. From the analysis it was calculated the parameter bone mineral density (BMD), express in g/cm2, that indicates the relation between mass of bone mineral content and area of examined bone segment. BMD data was compared to a range normalized by age, sex and ethnicity (BMD-N). RESULTS: The results of the scannnig of St. Nicholas' rib showed a BMD of 0.97g/cm2 with a BMD-N between 0.77 and 1.08g/cm2. Simultaneous measurements of the relic compared with a reference rib showed highlighted BMD of 0.84g/cm2 for the relic and 0.50g/cm2 for the reference rib. The St. Nicholas data are 168% higher than reference bone. All our measurements of the relic indicated a high bone mineral density, most likely due to the presence of a high concentration of calcium salts. A relatively higher mineral density of the relic was seen compared to the healthy subject's rib. From the history of St Nicholas' life, we know of the long imprisonment at the age of 51 in damp and unhealthy environment. The results of this study suggest that a good bone mineral density was maintained by the Saint even in old age. An additional element that can influence bone mineral density is diet, certainly different during the time of St. Nicholas. The good bone densitometry indicates that the Saint maintained a proper diet, with a generally fair state of health. CONCLUSION: For this first DXA analysis of the rib relic of Saint Nicholas was necessary a long and complex experimental work to modify standard technique procedure to particular and unusual sample and Create specific supports and complementary instruments. Perform DXA analysis on relics permit to obtain additional information to living conditions, economical situation, behaviours, diet, diseaes, conservations conditions of remains, change of life style in different age. Our experimental work, the first of its kind, creates the way to analyze precious relics that often include only few bone fragments and data obtained by our work can be useful for a better management and movement of fragile relics. We ourselves are working on a new challenge for the analysis of bone finds from shipwrecks found at the bottom of the sea.

Sickle cell diseases: What can nuclear medicine offer?

Sickle cell disease (SCD) is the best known haemoglobinopathy, caused by a mutation substituting valina for glutamic acid at position 6 of the beta-globin chain of adult hemoglobin A, resulting in hemoglobin S (HbS). The homozygous HbS disease (HbSS), an autosomal recessive disorder, is the most common form and the Mediterranean area, along with sub-Saharian African and India, have the highest prevalence (1%-15%). In particular, Sicily with a prevalence of 2%-5%, is among the most interested regions. However, migratory flows have led to a wider diffusion of the disease no longer confined to endemic areas. In Europe, the yearly estimate of affected births are 1,300 but more than 90% of children with SCD survive into adulthood thanks to screening programs and early available care; however, their lifespan remains shortened by two or three decades compared to general population. In Greece, the number of affected births surpassing 100,000 yearly and the total number of newborns carrying two deleterious genes, if no prevention measures are taken, is estimated to be about 120-130/year. Diagnosis of SCD is based on analysis of haemoglobin through protein electrophoresis or chromatography, that are cheap and widely available techniques, even if haemoglobin mass spectrometry and DNA analysis are techniques with high-throughput testing. Prenatal diagnosis is used in many European countries, so the number of affected newborns has significantly decreased during the last 3 years. Over the course of SCD, sickling process may cause acute and chronic abdominal pain due to vaso-occlusive crisis, bone pain often in long bones due to bone marrow infarction, chronic hemolytic anemia, splenic sequestration with rapid enlargement of the spleen, delayed sexual maturation and cholelithiasis, with important inter-indivuidual variability. Sickle hepatopathy reflects liver sickling process within hepatic sinusoids and includes gallstone disease, hepatic sequestration, hepatic sideroris, acute sickle cell hepatic crises (ASHC) and sickle cell intrahepatic cholestasis (SCIC). Clinically, it appears with fever, right upper quadrant pain, jaundice and increased serum liver function tests. These patients are repeatedly esposed to trasfused red cells that contributes to iron overload and may contribute to hepatic haemosiderosis. Increased bone turnover and resorption by osteoclasts and by marrow expansion due to activation of hematopoiesis. The hematopoietic system may expand physiologically. Computed tomography (CT) is an easily reproducible imaging method that allows the morphologic whole-body evaluation although with a high dose of radiation exposure and possible side effects from intravenous contrast media. Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive technique without radiation chosen to image cholangiopathy and may be followed by the execution of endoscopic retrograde cholangiopancreatography (ERCP) in case of gallstone disease. Otherwise it can be helpful in identifying extramedullary hematopoiesis sites. Dual-energy X-rays absorptiometry (DEXA) is performed to evaluate deficit of bone mineral density (BMD), in which reduction of osteoblastic activity, high risk for necrosis may induce to fragility fractures. We recently had the experience of a typical case of a 56 years old Albanian woman with SCD, with jaundice after a long history of recurrent vaso-occlusive crisis. She was submitted to splenectomy and cholecystectomy 5 years before and since then she was treated with hydroxyurea. Hemocromatosis was excluded by genetic analysis. Hepatic biopsy (Pearl's stain) showed sinusoidal dilatation and diffuse iron accumulation in hepatocytes and Kupffer cells. Endo-hepatic jaundice was observed in MRCP images. It was interesting that DEXA examination was within normal range in both right proximal femur. This may probably be due to the presence of sclerotic lesions in the vertebrae, as was seen in the CT images. Technetium-99m-methylen bisphosphonate (99mTc-MDP) skeletal scintigraphy is a higly sensitive whole-body diagnostic nuclear medicine technique able to evaluate early bone metabolic changes. Multimodality SPET/CT allows to correlate scintigraphic findings with anatomical images with higher sensitivity and specificity. The higher uptake of 99mTc-MDP in SCD patients is due to the activation of hematopoetic system and relies on the osteoblastic response to bone resorption as in our patient. The 99mTc-MDP scan may be better than fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) to show sclerotic lesions. Technetium-99m nanocolloids bone marrow scintigraphy (BMS) provides information about the assessment of the reticulum-endothelial system (RES), the whole-body distribution of functional red bone marrow and the presence and the extent of extramedullary hematopoiesis, especially in liver, spleen and bone marrow. Fluorine-18-FDG PET/CT completes the whole-body assessment with an integrated multimodal approach with high spatial resolution that evaluates the metabolic activity and the standardized uptake value (SUV) in SCD patients. Modern genetic diagnosis and gene treatment give promise for having fewer cases of SCD in the future.

Chronic coffee consumption and striatal DAT-SPECT findings in Parkinson's disease.

Coffee may interfere with the dopaminergic transmission, and this action would possibly enhance motor activity and exert an antidyskinetic effect in Parkinson's disease (PD). This study aimed to see whether coffee habit could be associated with change in striatal dopamine active transporter (DAT)-single photon emission computed tomography (SPECT) imaging in PD. A total of 83 PD patients (71 current coffee drinkers and 12 never drinkers) underwent a DAT-SPECT study, using [123I]FP-CIT as radionuclide. Socio-demographic and clinical information as well as smoking habit was collected at the time of imaging acquisition. The Unified Parkinson's Disease Rating Scale part III was used to evaluate disease severity. On multivariable analysis, chronic coffee consumption was not associated with any significant change in striatal uptake of the radionuclide. However, the number of years patients drunk coffee was correlated with a significant increase in age at PD onset (p < 0.001). Confirming a previous report, current cigarette smoking was associated with a reduction of radionuclide uptake in putamen and caudate (p < 0.001).

Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal (n = 16), ovarian (n = 5), and breast (n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (<6, 6, 12, >12), number of hyperthermia sessions (<12, 12, 24, >24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles (p = 0.015) and to number of HT sessions (p < 0.001) performed. Both overall survival (OS) and time to progression (TTP) were influenced by the number of chemotherapy cycles (p < 0.001) and HT sessions (p < 0.001) performed. Our preliminary data, that need to be confirmed in larger studies, suggest that the combined treatment of bevacizumab-based chemotherapy with HT has a favorable tumor response, is feasible and well tolerated, and offers a potentially promising option for metastatic cancer patients.

Pediatric Hodgkin Lymphoma: Predictive value of interim 18F-FDG PET/CT in therapy response assessment.

We investigated the prognostic value of interim F-FDG PET/CT (PET-2) in pediatric Hodgkin lymphoma (pHL), evaluating both visual and semiquantitative analysis.Thirty pHL patients (age ≤16) underwent serial F-FDG PET/CT: at baseline (PET-0), after 2 cycles of chemotherapy (PET-2) and at the end of first-line chemotherapy (PET-T). PET response assessment was carried out visually according to the Deauville Score (DS), as well as semiquantitatively by using the semiquantitative parameters reduction from PET-0 to PET-2 (ΔΣSUVmax0-2, ΔΣSUVmean0-2). Final clinical response assessment (outcome) at the end of first-line chemotherapy was the criterion standard, considering patients as responders (R) or nonresponders (NR). Disease status was followed identifying patients with absence or relapsed/progression disease (mean follow-up: 24 months, range 3-78).Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of visual and semiquantitative assessment were calculated; furthermore, Fisher exact test was performed to evaluate the association between both visual and semiquantitative assessment and outcome at the end of the first-line chemotherapy. The prognostic capability of PET-2 semiquantitative parameters was calculated by ROC analysis and expressed as area under curve (AUC). Finally, progression-free survival (PFS) was analyzed according to PET-2 results based on the 5-point scale and semiquantitative criteria, using the Kaplan-Meier method.Based on the outcome at the end of first-line chemotherapy, 5 of 30 patients were NR, the remnant 25 of 30 were R. Sensitivity, specificity, PPV, NPV, and accuracy of visual analysis were 60%,72%,30%,90%,70%; conversely, sensitivity, specificity, PPV, NPV, and accuracy of semiquantitative assessment were 80%, 92%, 66.7%, 95.8%, 90%. The highest AUC resulted for ΔΣSUVmax0-2 (0.836; cut-off <12.5; sensitivity 80%; specificity 91%). The association between ΔΣSUVmax0-2 and outcome at the end of first-line chemotherapy resulted to have a strong statistical significance (P = 0.0026). Both methods demonstrated to influence PFS, even if the semiquantitative assessment allowed a more accurate identification of patients with a high risk of treatment failure (P = 0.005).Our preliminary results showed that PET-2 visual assessment, by using Deauville criteria, can be improved by using the semiquantitative analysis. The SUV max reduction (ΔΣSUVmax0-2) evaluation might provide a support for the interpretation of intermediate scores, predicting with good confidence those patients who will have a poor outcome and require alternative therapies.

[The PET/CT with 18F-fluorocholine in the diagnosis of gliomatosis cerebri type 2]. / La tomografia a emissione di positroni con 18F-fluorocolina nella gliomatosi cerebrale di tipo II.

In a patient with cerebral gliomatosis type II MRI revealed a large area of altered signal in the temporal region, parietal and occipital lobes associated with a single nodule with perilesional contrast enhancement, which showed increased uptake on PET/CT with 18F-FCH, characterizing heterogeneous cellularity of the tumor.

Long-term functional assessment of antegrade colonic enema for combined incontinence and constipation using a modified Marsh and Kiff technique.

PURPOSE: Constipation and fecal incontinence can severely affect quality of life for patients, particularly when simultaneously present. Malone antegrade colonic enema enables periodic colonic emptying, thus preventing uncontrolled passage of feces and constipation. METHODS: Eleven patients with fecal incontinence and severe constipation or perineal colostomy after Miles' operation underwent a modified Marsh and Kiff ileostomy for antegrade colonic enema. Before and after surgery, the patients were fully evaluated for gastrointestinal functions, including gallbladder and stomach emptying time, H(2)-breath test, colonic transit time, dynamic defecography, and anorectal manometry. The severity of incontinence and constipation was scored preoperatively and postoperatively by using the American Medical System score and Cleveland Clinic Constipation scale, respectively, whereas the quality of life was measured by the Gastrointestinal Quality of Life Index. The surgical technique involved division of the terminal ileum 10 to 15 cm from the ileocecal valve, anastomosis and intussusception of the ileum with the cecum, narrowing of the ileal conduit with a linear stapler, and a small, introflexed ileostomy with an advanced skin flap. RESULTS: During the postoperative period, the mean American Medical System score decreased significantly from 77 to 11 (P<0.01) and the mean Cleveland Clinic Constipation score from 23 to 8.5 (P<0.01) with a significant improvement of quality of life. Antegrade colonic enema did not affect gallbladder, gastric, or orocecal transit time, which remained comparable with baseline. Colonic scintigraphy showed that antegrade colonic enema was efficient to clean the whole colon and rectum, leaving only 24 (range, 6-40) percent of the initial radioactivity after 30 minutes. Ileal manometry confirmed the presence of a high-pressure zone, preventing accidental reflux. CONCLUSIONS: Modified Marsh and Kiff technique is a safe and effective surgical option to treat patients with combined fecal incontinence and severe constipation and those with perineal colostomy after Miles. It should be recommended as a last option before colostomy.