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PURPOSE Biomarkers for treatment personalization in metastatic castration-resistant prostate cancer (mCRPC) could help improve patient outcomes. Multiple tests on blood have reported associations with poorer outcome, including serum lactate dehydrogenase (LDH), chromogranin A (CGA), neutrophil:lymphocyte ratio (NLR), and, recently, copy number (CN) of androgen receptor (AR) in plasma DNA. Biologic data suggest an association between choline uptake and AR signaling. We aimed to integrate 18F-fluorocholine (FCH) uptake on positron emission tomography/computed tomography (PET/CT) scanning with plasma AR CN and other routinely obtained circulating biomarkers to evaluate their association with outcome. MATERIALS AND METHODS We determined plasma AR CN by digital droplet polymerase chain reaction from 105 mCRPC samples collected before abiraterone (n = 65) or enzalutamide (n = 40) therapy in the before (n = 26) and after (n = 79) chemotherapy settings. Pretreatment serum LDH, CGA, and NLR were also measured. FCH-PET/CT scan was performed at baseline, and maximum standardized uptake value (SUVmax), total lesion activity (TLA), and metabolic tumor volume (MTV) were calculated. Main end points were the correlation of FCH-PET/CT parameters with circulating biomarkers and their impact on outcome. RESULTS Plasma AR CN gain was observed in 27 patients (25.7%), and it correlated significantly with higher median SUVmax, TLA, and MTV values ( P < .001). Kaplan-Meier curves showed significantly worse progression-free survival and overall survival in patients with plasma AR gain and higher SUVmax, TLA, and MTV values ( P < .001 in each prognostic group). Conversely, no association was reported for prostate-specific antigen response. On multivariable analysis of overall survival, we showed as independent factors AR gain (hazard ratio [HR], 1.92; 95% CI, 1.07 to 3.47; P = .029), presence of visceral metastasis (HR, 3.04; 95% CI, 1.66 to 5.58; P = < .001), LDH (HR, 2.95; 95% CI, 1.72 to 5.05; P < .001), NLR (HR, 3.51; 95% CI, 2.14 to 5.74; P < .001), serum CGA (HR, 3.36; 95% CI, 1.99 to 5.67; P < .001), and MTV (HR, 2.09; 95% CI, 1.25 to 3.50; P = .005). CONCLUSION Our results indicate the potential usefulness of integrating functional imaging with plasma DNA analysis and other noninvasive biomarkers as a tool to improve treatment selection for CRPC. A larger prospective evaluation is warranted.

Given a complex analytic germ $(X, 0)$ in $(\mathbb C^n, 0)$, the standard Hermitian metric of $\mathbb C^n$ induces a natural arc-length metric on $(X, 0)$, called the inner metric. We study the inner metric structure of the germ of an isolated complex surface singularity $(X,0)$ by means of an infinite family of numerical analytic invariants, called inner rates. Our main result is a formula for the Laplacian of the inner rate function on a space of valuations, the non-archimedean link of $(X,0)$. We deduce in particular that the global data consisting of the topology of $(X,0)$, together with the configuration of a generic hyperplane section and of the polar curve of a generic plane projection of $(X,0)$, completely determine all the inner rates on $(X,0)$, and hence the local metric structure of the germ. Several other applications of our formula are discussed in the paper., Comment: Proposition 5.3 strengthened, exposition improved, some typos corrected, references updated. 42 pages and 10 figures. To appear in Geometry & Topology

To evaluate the clinical value of 68Ga-PSMA PET/CT negativity in patients with biochemical recurrent prostate cancer (BCR). One hundred three BCR patients (median age, 70 years; median PSA, 0.47 ng/mL) with negative 68Ga-PSMA PET/CT, followed up for at least 1 year, were retrospectively identified in a database of 1003 consecutive patients undergoing 68Ga-PSMA PET/CT for BCR. Clinical recurrence (CR) was determined or excluded on follow-up imaging selected as per clinical practice. Clinical recurrence-free survival (CRFS) was computed from the date of negative 68Ga-PSMA PET/CT to the date of evident disease; frequencies of CRFS were described as per ISUP patient subset (subset 1: ISUP grades 1 and 2; subset 2: ISUP grade 3; subset 3: ISUP grades 4 and 5) and other conventional variables. In 57 patients out of 103 (55.3%), CR was detected in the prostatic fossa (45.6%), nodes (38.6%), and bone (15.8%). The median CRFS was 15.4 months (range, 12.1–20.5), with a CRFS at 12 months in 61.4% of cases (range, 50.9–70.4) whereas the 24-month CRFS was 34.8% (range, 24–45.8). ISUP subset 1 benefited from significantly longer CRFS compared to subset 2 and subset 3 (median CRFS, 20.5 months, 12.6 months, and 12.1 months, respectively). ISUP subset 3 had significantly poorer 24-month CRFS (9.3%) compared to subset 1 (47.8%) and subset 2 (33.5%). At the univariate and multivariate analyses, the ISUP subset was the only significant risk factor for clinical relapse; ISUP subset 3 and subset 2 patients held a higher risk of CR compared to subset 1 patients (HR of 2.75 [1.35–5.57] for subset 3 versus subset 1; HR of 2.08 [1.11–3.88] for subset 2 versus subset 1). 68Ga-PSMA PET/CT negativity in early BCR patients (PSA

Purpose The objective of this study was to evaluate a set of radiomics-based advanced textural features extracted from 18F-FLT-PET/CT images to predict tumor response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (BC). Materials and Methods Patients with operable (T2-T3, N0-N2, M0) or locally advanced (T4, N0-N2, M0) BC were enrolled. All patients underwent chemotherapy (six cycles every 3 weeks). Surgery was performed within 4 weeks of the end of NCT. The MD Anderson Residual Cancer Burden calculator was used to evaluate the pathological response. 18F-FLT-PET/CT was performed 2 weeks before the start of NCT and approximately 3 weeks after the first cycle. The evaluation of PET response was based on EORTC criteria. Standard uptake value (SUV) statistics (SUVmax, SUVpeak, SUVmean), together with 148 textural features, were extracted from each lesion. Indices that are robust against contour variability (ICC test) were used as independent variables to logistically model tumor response. LASSO analysis was used for variable selection. Results Twenty patients were included in the study. Lesions from 15 patients were evaluable and analyzed: 9 with pathological complete response (pCR) and 6 with pathological partial response (pPR). Concordance between PET response and histological examination was found in 13/15 patients. LASSO logistic modelling identified a combination of SUVmax and the textural feature index IVH_VolumeIntFract_90 as the most useful to classify PET response, and a combination of PET response, ID range, and ID_Coefficient of Variation as the most useful to classify pathological response. Conclusions Our study suggests the potential usefulness of FLT-PET for early monitoring of response to NCT. A model based on PET radiomic characteristics could have good discriminatory capacity of early response before the end of treatment.

In this paper we use motivic integration and non-archimedean analytic geometry to study the singularities at infinity of the fibers of a polynomial map $f\colon \mathbb A^d_\mathbb C \to \mathbb A^1_\mathbb C$. We show that the motive $S_{f,a}^{\infty}$ of the motivic nearby cycles at infinity of $f$ for a value $a$ is a motivic generalization of the classical invariant $\lambda_f(a)$, an integer that measures a lack of equisingularity at infinity in the fiber $f^{-1}(a)$. We then introduce a non-archimedean analytic nearby fiber at infinity $\mathcal F_{f,a}^{\infty}$ whose motivic volume recovers the motive $S_{f,a}^{\infty}$. With each of $S_{f,a}^{\infty}$ and $\mathcal F_{f,a}^{\infty}$ can be naturally associated a bifurcation set; we show that the first one always contains the second one, and that both contain the classical topological bifurcation set of $f$ whenever $f$ has isolated singularities at infinity.

Introduction: 68Ga-PSMA is a labelled ligand to a membrane protein overexpressed in many prostate cancer cells and has raised its interest to be highly specific in PET imaging for detection and staging of prostate cancers. DW-MRI is a standard technique that provides quantitative information about tumor cellularity and tissue structure is a useful tool for the detection and staging of prostate cancer in clinical practice. This study investigates the correlation between SUVmax and tumour heterogeneity computed from DWI sequences. Materials and Methods: 17 patients (age range, 49-75 years; mean, 64.3 years) of a prospective study aiming at multi-cohort investigation for clinical impact of mp-3TMRI and 68Ga-PSMA PET/CT in diagnosis of clinically-significant prostate cancer and presurgical staging. After co-registering MRI and PET sequences, Regions of Interest (ROIs) were manually delineated around prostate in MRI/T2 and the cancer lesion in the dominant sequence (high values of DWI or T2). SUVmax was computed on PET images and 60%-threshold of SUVmax was used for lesion contouring. A compound texture feature related to tumour heterogeneity (Hc) was computed within prostate ROIs in DWI and the outcome represented with colorimetric maps. The highest regions were extracted by automatic contouring. Average Hc (DWI) and SUVmax (PET) were computed on the co-registered slices and the Spearman rank correlation (ρ) was assessed. Results: SUVmax ranges from [1.6-101.0] and Hc through [37.9 -50.6]. Regions highlighted by Hc are usually much greater than those detected by SUVmax thresholding and always include the region outlined by radiologists. 13 patients show ρ≥0.7, 3 with ρ≥0.5 and 1 only with ρ≥0.25. For 11 patients (65% of cases) the amount of PET slices pointing out malignant SUV peaks is greater than DWI slices showing high Hc values, with Hc ROIs better depicting tumour extent. For 3 patients (17.5%) PET and Hc-DWI show equivalent performance in tumour detection and in 3 cases only, Hc points out more slices with suspect tumour ROIs. However, in all cases SUV and Hc show the same trend, with the highest values around central slices and a much greater increasing rate for SUV. Conclusions: The outcomes of this study reveal a rank correlation between heterogeneity of cellularization and the expression of the membrane receptor of PSMA. The reason of such correlation requires deeper investigations and could be confirmed after examining a wider cohort. Hc result a promising compound feature for outlining malignant ROIs extent to be employed together with PET sequences for validating tumour side. A deeper analysis is required for those few cases showing weak or even poor correlation between SUV and Hc.

The role of 18F–choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42–90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. We observed a median SMTV of 130 cm3, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p

Evidence supporting rechallenge in patients responding to first exposure to trabectedin is limited. We report on a 39-year-old woman with advanced high-grade undifferentiated sarcoma (US) retreated twice with trabectedin after first response. The patient presented in June 2006 with an abdominal mass originating from the rear fascia of the rectus abdominis. Staging examinations did not indicate metastases and she underwent surgery; pathology showed a high-grade (FNCLCC G3) US. Subsequently, the patient received five cycles of adjuvant chemotherapy with epirubicin and ifosfamide. In February 2009 a computed tomography (CT) scan showed an abdominal mass involving the transverse mesocolon. R0 surgery was performed. In September 2009, peritoneal lesions appeared. Trabectedin was initiated at a dose of 1.5 mg/m2 by a 24 h intravenous infusion every 3 weeks, without relevant toxicity. After six cycles (March 2010), CT and PET-CT scans showed complete disappearance of metastases. In February 2012, new secondary lesions in the subdiaphragmatic region and a peritoneal lesion appeared. We rechallenged the patient with the same schedule of trabectedin; a complete response was achieved after two cycles. In October 2013, new secondary lesions in the subdiaphragmatic region and a retroperitoneal lesion were found. We rechallenged with the same schedule of trabectedin; PET-CT scans after two cycles showed complete response on the subdiaphragmatic lesion. Radiotherapy on the retroperitoneal lesion was performed. The patient underwent a total of 18 cycles and remains free from radiologically detectable disease. We report complete radiological remission after two rechallenges with trabectedin in a patient with previously responding high-grade US.

We characterize sandwiched singularities in terms of their link in two different settings. We first prove that such singularities are precisely the normal surface singularities having self-similar non-archimedean links. We describe this self-similarity both in terms of Berkovich analytic geometry and of the combinatorics of weighted dual graphs. We then show that a complex surface singularity is sandwiched if and only if its complex link can be embedded in a Kato surface in such a way that its complement remains connected., 35 pages

We study the Galois descent of semi-affinoid non-archimedean analytic spaces. These are the non-archimedean analytic spaces which admit an affine special formal scheme as model over a complete discrete valuation ring, such as for example open or closed polydiscs or polyannuli. Using Weil restrictions and Galois fixed loci for semi-affinoid spaces and their formal models, we describe a formal model of a $K$-analytic space $X$, provided that $X\otimes_KL$ is semi-affinoid for some finite tamely ramified extension $L$ of $K$. As an application, we study the forms of analytic annuli that are trivialized by a wide class of Galois extensions that includes totally tamely ramified extensions. In order to do so, we first establish a Weierstrass preparation result for analytic functions on annuli, and use it to linearize finite order automorphisms of annuli. Finally, we explain how from these results one can deduce a non-archimedean analytic proof of the existence of resolutions of singularities of surfaces in characteristic zero., Comment: Exposition improved and minor modifications. 37 pages. To appear in Math. Z

Urea-based prostate-specific membrane antigen (PSMA) ligands labelled withKidney uptake (SUVmax) was calculated in nine patients undergoingIn patients receiving the A-infusion, mean SUVOur preliminary findings indicate that mannitol may play a role in reducing off-target

We define a non-Archimedean analytic version of the link of a singularity, and we use it to study surfaces over an algebraically closed field. This yields a characterization of log essential valuations.

PURPOSE: This study aims to evaluate the role of (11)C-choline PET/CT in patients with biochemical relapse after radical prostatectomy (RP) showing prostate-specific antigen (PSA) values lower than 0.5 ng/mL. METHODS: We performed (11)C-choline PET/CT in 71 consecutive patients previously treated with RP showing PSA values lower than 0.5 ng/mL. (11)C-Choline PET/CT was performed following standard procedure. (11)C-Choline PET/CT-positive findings were validated by transrectal ultrasonography + biopsy, repeated (11)C-choline PET/CT, other conventional imaging modality, and histology. RESULTS: (11)C-Choline PET/CT was true positive in 15/71 (21.1%). (11)C-Choline uptake was observed in pelvic lymph nodes (7/71; 9.9%), in the prostatic bed (7/71; 9.9%), and in bone (1/71; 1.4%). Mean PSA, PSA doubling time (PSAdt), and PSA velocity (PSAvel) values ± SD in (11)C-choline PET/CT-positive patients was 0.37 ± 0.1 ng/mL, 3.4 ± 2.1 months, and 0.05 ± 0.1 ng/mL/yr, respectively. (11)C-Choline PET/CT was false negative in 2 patients and false positive in 1 patient. Among all variables, only PSAdt and the ongoing hormonal treatment were statistically significant in the prediction of a positive (11)C-choline PET/CT at multivariate analysis. CONCLUSIONS: (11)C-Choline PET/CT could be used early after biochemical failure even if PSA values are very low, preferentially in hormonal resistant patients showing fast PSA kinetics. An early detection of the site of relapse could lead to a personalized and tailored treatment.

Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs. From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6–8 weeks), according to kidney and bone marrow parameters. Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P

Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with 68Ga or 177Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of 68Ga-PSMA. Kidney uptake (SUVmax) was calculated in nine patients undergoing 68Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after 68Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after 68Ga-PSMA administration (B-infusion). In patients receiving the A-infusion, mean SUVmax increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUVmax decreased by 24.3% and 22.4% in the right and left kidney, respectively. Our preliminary findings indicate that mannitol may play a role in reducing off-target 68Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before 68Ga-PSMA injection. These results warrant dosimetric studies in patients treated with 177Lu-PSMA to find the best scheme for mannitol administration.

Background: Pancreatic serous cystic tumors are considered to have a benign biological and clinical course with only few malignant cases. Methods: We retrospectively analyzed data from 26 patients affected by serous cystic tumors consecutively observed in our Pancreas Unit. We explored the different clinical pictures in operated and nonoperated patients. Results: Eighteen of the 26 patients were female (69%), median age at diagnosis was 61.5 years and 20 patients (77%) underwent surgery. The median diameter of the tumors was greater in patients who underwent surgery than in those who did not (5.5 versus 2.3 cm, p < 0.001). Major pancreatic resections were carried out in 15 of the 20 operated patients (75%). Postoperative morbidity and mortality were 20 and 5%, respectively. During follow-up, there was no observed development of malignancy or any significant increase in the diameter of the lesion among nontreated patients. Conclusions: In asymptomatic patients with a clear imaging diagnosis of serous cystic tumor a wait and see management should be recommended, with a careful follow-up. Surgery should be suggested in symptomatic patients or when the preoperative diagnosis is doubtful.

Objectives There are no data available that evaluate the possible modifications of the quality of life during the clinical course of chronic pancreatitis. To evaluate the outcome for patients with chronic pancreatitis in a 2-year follow-up study. Methods The Short Form 12 Health Survey Italian version questionnaire was used for the purpose of the study. The questionnaire generates 2 summary scores: the physical component summary (PCS-12) and the mental component summary (MCS-12). Eighty-three patients with chronic pancreatitis were studied with a mean (+/-SD) interval time of 2.3 +/- 0.2 years between the first and the second evaluation. Results There was a significant increase in the frequency of diabetes mellitus (P = 0.008), nonpancreatic surgery (P = 0.016), and comorbidities (P = 0.004). The PCS-12 (44.7 +/- 10.7) and MCS-12 (44.1 +/- 13.3) were not significantly different in comparison with the baseline evaluation (PCS-12, 43.7 +/- 9.8; MCS-12, 44.3 +/- 11.4). The PCS-12 score worsened in 17 (20.5%) patients, 44 (53.0%) had a stable PCS-12 score, and the remaining 22 (26.5%) improved their PCS-12 score. Regarding the mental score, 15 (18.1%) patients worsened, 52 (62.7%) had a stable MCS-12 score, and the remaining 16 (19.3%) improved their MCS-12 score. Only age at diagnosis was significantly related to the change of the MCS-12 score (P = 0.028, positive relationship). Conclusions The information given by quality-of-life assessment should be routinely included in the work-up of patients affected by chronic pancreatitis to select those patients with severely impaired physical and mental scores, and to plan an intensive program of medical and psychological follow-up.

We define normalized versions of Berkovich spaces over a trivially valued field $k$, obtained as quotients by the action of $\mathbb R_{>0}$ defined by rescaling semivaluations. We associate such a normalized space to any special formal $k$-scheme and prove an analogue of Raynaud's theorem, characterizing categorically the spaces obtained in this way. This construction yields a locally ringed $G$-topological space, which we prove to be $G$-locally isomorphic to a Berkovich space over the field $k((t))$ with a $t$-adic valuation. These spaces can be interpreted as non-archimedean models for the links of the singularities of $k$-varieties, and allow to study the birational geometry of $k$-varieties using techniques of non-archimedean geometry available only when working over a field with non-trivial valuation. In particular, we prove that the structure of the normalized non-archimedean links of surface singularities over an algebraically closed field $k$ is analogous to the structure of non-archimedean analytic curves over $k((t))$, and deduce characterizations of the essential and of the log essential valuations, i.e. those valuations whose center on every resolution (respectively log resolution) of the given surface is a divisor., Several corrections and improvements. New result added, Theorem 10.8, proving a characterization of essential valuations. 51 pages. To appear in Transactions of the AMS

We study whether a given tropical curve $\Gamma$ in $\mathbb{R}^n$ can be realized as the tropicalization of an algebraic curve whose non-archimedean skeleton is faithfully represented by $\Gamma$. We give an affirmative answer to this question for a large class of tropical curves that includes all trivalent tropical curves, but also many tropical curves of higher valence. We then deduce that for every metric graph $G$ with rational edge lengths there exists a smooth algebraic curve in a toric variety whose analytification has skeleton $G$, and the corresponding tropicalization is faithful. Our approach is based on a combination of the theory of toric schemes over discrete valuation rings and logarithmically smooth deformation theory, expanding on a framework introduced by Nishinou and Siebert., Comment: 16 pages, introduction improved and other minor modifications, to appear in IMRN, comments very welcome!

The aim of this work was to preliminarily evaluate the sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of 68Ga-citrate PET/CT in a population of patients with suspected bone infections. Methods: We enrolled 31 patients with suspected osteomyelitis or diskitis who underwent a total of forty 68Ga-citrate PET/CT scans. The results were compared with different combinations of diagnostic procedures (MRI, radiography, CT, or white blood cell scintigraphy), biopsy (when diagnostic), and follow-up data (at least 1 y) to determine the performance of 68Ga-citrate PET/CT. Results: We found a sensitivity of 100%, a specificity of 76%, a positive predictive value of 85%, a negative predictive value of 100%, and an overall accuracy of 90%. Conclusion: Although preliminary, these data confirm a possible role for 68Ga-citrate in the diagnosis of bone infections, especially in consideration of its favorable characteristics.

2- [(18)F]-fluoro-2-deoxy-D-glucose (FDG) is the radiopharmaceutical most frequently used for clinical positron emission tomography (PET). However, FDG cannot be used for many oncological, cardiological, or neurological conditions, either because the abnormal tissue does not concentrate it, or because the tissues under investigation demonstrate high physiological glucose uptake. Consequently, alternative PET tracers have been produced and introduced into clinical practice. The most important compounds in routine practice are (11)C-choline and (18)F-choline, mainly for the evaluation of prostate cancer; (1)C-methionine for brain tumours; (118)F-DOPA ((18)F-deoxiphenilalanine) for neuroendocrine tumours and movement disorders; (68)Ga-DOTANOC (tetraazacyclododecanetetraacetic acid-[1-Nal3]-octreotide) and other somatostatin analogues for neuroendocrine tumours; 11C-acetate for prostate cancer and hepatic masses and 18F-FLT (3-deoxy-3-fluorothymidine) for a number of malignant tumours. Another impetus for the development of new tracers is to enable the investigation of biological processes in tumours other than glucose metabolism. This is especially important in the field of response assessment, where there are new agents that are targeted more specifically at angiogenesis, hypoxia, apoptosis and other processes.

To evaluate the adhesion molecule time course in the early phases of acute pancreatitis and to explore the usefulness of these proteins in assessing the severity of the disease. Fifteen consecutive acute pancreatitis patients (10 patients with the mild and 5 with the severe disease) admitted to the hospital within 6 hours after the onset of pain and 15 age- and sex-matched healthy subjects.Vascular cell adhesion molecule 1, intercellular adhesion molecule 1, E-selectin, P-selectin, and L-selectin were quantified on hospital admission and for the following 2 days.Acute pancreatitis patients had vascular cell adhesion molecule 1 and P-selectin concentrations significantly lower and L-selectin concentrations significantly higher than the healthy subjects. Only E-selectin was significantly higher in severe than in mild disease (P = 0.029); a value of E-selectin ranging from 3.83 to 3.92 ng/mL was the best cutoff value for differentiating severe from mild acute pancreatitis (sensitivity: 60.0%, specificity: 90.0%, cases correctly classified: 80%). E-selectin and P-selectin entered the multivariate logistic regression analysis, and a score was calculated showing a sensitivity of 93.3% and a specificity of 86.7% in identifying the patients with severe pancreatitis.This score seems to be useful for the early assessment of the severity of acute pancreatitis.

Pancreatic serous cystic tumors are considered to have a benign biological and clinical course with only few malignant cases.We retrospectively analyzed data from 26 patients affected by serous cystic tumors consecutively observed in our Pancreas Unit. We explored the different clinical pictures in operated and nonoperated patients.Eighteen of the 26 patients were female (69%), median age at diagnosis was 61.5 years and 20 patients (77%) underwent surgery. The median diameter of the tumors was greater in patients who underwent surgery than in those who did not (5.5 versus 2.3 cm, p0.001). Major pancreatic resections were carried out in 15 of the 20 operated patients (75%). Postoperative morbidity and mortality were 20 and 5%, respectively. During follow-up, there was no observed development of malignancy or any significant increase in the diameter of the lesion among nontreated patients.In asymptomatic patients with a clear imaging diagnosis of serous cystic tumor a wait and see management should be recommended, with a careful follow-up. Surgery should be suggested in symptomatic patients or when the preoperative diagnosis is doubtful.

Fecal calprotectin determination has been demonstrated to be useful in diagnosing various inflammatory diseases of the gastrointestinal tract; however, data available for patients with pancreatic diseases are scarce. Our aim was to assess fecal calprotectin in order to evaluate the presence of intestinal inflammation in patients with pancreatic disease. Eligible patients with suspected pancreatic illness were enrolled, and in all of them fecal calprotectin and elastase-1, as well as serum amylase and lipase activities, were assayed using commercially available kits. A total of 90 subjects (47 men, 43 women, mean age 58.6 ± 14.9 years) were enrolled: 20 (22.2%) had chronic pancreatitis; 15 (16.7%) had pancreatic cancer; six (6.7%) had chronic nonpathological pancreatic hyperenzymemia; 16 (17.8%) had nonpancreatic diseases; and 23 (25.6%) had no detectable diseases. Diarrhea was present in 19 patients (21.1%). In univariate analyses, the presence of diarrhea and low fecal elastase-1 concentrations were significantly associated (P = 0.019 and P = 0.002, respectively) with abnormally high fecal calprotectin concentration, and the multivariate analysis demonstrated that low fecal elastase-1 concentration was the only variable independently associated with a high fecal calprotectin concentration. Pancreatic insufficiency may cause intestinal inflammation, probably because of a modification of the intestinal ecology.

Human exhaled breath contains many molecules either present as gases or occurring in a soluble form in the vapor of the breath. This study was designed to evaluate the substances present in the exhaled breath of chronic pancreatitis (CP) patients.Thirty-one consecutive CP patients (11 with exocrine insufficiency) and 31 healthy subjects (HS) were studied.Ninety-eight different substances were analyzed using a mass spectrometer on a breath sample from all subjects and on each respective ambient air sample.H(2)S, NO and a substance having a molecular mass of 66 u (M66) were those which had significantly higher concentrations in CP patients than in HS after adjustment for the ambient air; the estimated increases attributable to the disease were 14% (p = 0.040) for H(2)S, 84% (p = 0.006) for M66 and 50% (p = 0.033) for NO, but the three volatile compounds showed poor diagnostic accuracy in differentiating CP patients from HS (AUC-ROC: 0.664, 0.715, and 0.602 for H(2)S, M66, and NO, respectively). Finally, no significant differences of H(2)S, M66, and NO were found between patients with and without alcoholic pancreatitis as well as between patients with and without pancreatic insufficiency.Exhaled breath analysis can rapidly and easily assess the presence of volatile compounds (H(2)S, NO and a substance having a molecular mass of 66 u) which may have properties capable of explaining, at least in part, the pathogenesis of CP.

The aim of this paper was to review the data existing in the English literature on the quality of life in patients who undergo surgical resection of the pancreatic gland either for benign or for malignant diseases. MEDLINE, Web of Science, and ScienceDirect were browsed in order to select the data existing in the literature on quality of life and pancreatic surgery. Alerts received by e-mail were also taken into account. Only full text papers were selected. Of the 161 papers found, only 13 papers were evaluated for the purpose of this study: 11 focused on surgical resective procedures in chronic pancreatitis and two focused their interest on assessing the quality of life related to resective procedures in pancreatic neoplasms. Despite the scarcity of studies assessing the quality of life in patients who underwent pancreatic surgery, there is the need to routinely assess well-being in patients who have been operated on.

The only potentially radical treatment for pancreatic cancer is the removal of the tumor which can be performed by total or subtotal surgical resection of the pancreas; this is possible in the early stages of the disease when the tumor is confined to the pancreatic gland without metastasis to the liver, lymph nodes and/or the peritoneum, or involvement of the vascular system such as the celiac trunk and its branches and the superior mesenteric artery. In this paper, we describe the accuracy of computed tomography and positron emission tomography in the diagnosis of exocrine pancreatic cancer.

Background SF-12™ Health Survey, and European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 are the two main questionnaires proposed and validated for assessing the quality of life in chronic pancreatitis. Aims To evaluate the role of the information furnished by both the SF-12™ Health Survey and European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 questionnaires, and to determine which of these two questionnaires may be considered more efficacious, in clinical practice, in describing the quality of life of patients with chronic pancreatitis. Patients We studied 163 consecutive patients with proven chronic pancreatitis. Methods The Italian version of the SF-12™ Health Survey and the Italian neutral version of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 Version 3.0 questionnaires were administered. Results Pancreatic pain was the only clinical variable able to significantly impair the SF-12™ Health Survey component summaries as well as all domains of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30, while body mass index was positively related to the physical component summary-12 and to the domains of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30. A high level of reliability of the domains/scores of the two questionnaires in evaluating the quality of life in patients with chronic pancreatitis was found and two main factors were identified. These two factors were mainly related to the two SF-12™ Health Survey summary components. Conclusions From a practical point of view, the SF-12™ Health Survey is more reliable and easier to use in routine clinical practice than the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30.

Acute pancreatitis represents the 0.15-1.5% of all diagnoses in the Emergency Room. Biliary diseases and alcohol abuse are the two mainly etiological factors of this illness in Italy. From a clinical point of view, the course of alcoholic and biliary acute pancreatitis is the same; however, because the endoscopic retrograde cholangiopancreatography associated with endoscopic sphincterotomy can prevent further complications in patients with severe biliary pancreatitis, it is important to early recognize the biliary origin of the disease. On the other hand, the identification of alcoholic origin of pancreatitis can prevent interventional procedures not useful in this kind of patients. In this paper we will assess the markers able to early identify the etiology of this acute illness such as the liver function tests and the lipase/amylase ratio.

In recent years, a number of articles have been published on the treatment of acute pancreatitis in experimental models and most of them were published about animals with mild disease. However, it is difficult to translate these results into clinical practice. For example, infliximab, a monoclonal TNF antibody, was experimentally tested in rats and it was able to significantly reduce the pathologic score and serum amylase activity, and also alleviate alveolar edema and acute respiratory distress syndrome; no studies are available in clinical human acute pancreatitis. Another substance, such as interleukin 10, was efficacious in decreasing the severity and mortality of lethal pancreatitis in rats, but seems to have no effect on human severe acute pancreatitis. Thus, the main problem in acute pancreatitis, especially in the severe form of the disease, is the difficulty of planning clinical studies capable of giving hard statistically significant answers regarding the benefits of the various proposed therapeutic agents previously tested in experimental settings. According to the pathophysiology of acute pancreatitis, we may re-evaluate the efficacy of the drugs already available, such as gabexate mesilate, lexipafant and somatostatin which should be probably administered in a different manner. Of course, also in this case, we need large studies to test this hypothesis. Another great problem is prevention of the infection of pancreatic necrosis. A randomized study has been published to test the hypothesis that probiotics and specific fibres used as supplements in early enteral nutrition may be effective in reducing pancreatic sepsis and the number of surgical interventions. A study named PROPATRIA (Probiotic Prophylaxis in Patients with Predicted Severe Acute Pancreatitis) has been planned to give a more robust confirmation to the previous study. Furthermore, the open question of the prevention of the fungal infection of necrosis is still being debated. Finally, the prevention of pain relapse after oral feeding in patients with mild or severe acute pancreatitis should be explored. Even if some studies exist on this issue, the question of optimal treatment is still unanswered. As in other diseases, obtaining results when treating patients with acute pancreatitis is difficult and will take continuous small steps.

In recent years, a number of articles have been published on the treatment of acute pancreatitis in experimental models and most of them concerned animals with mild disease. However, it is difficult to translate these results into clinical practice. For example, infliximab, a monoclonal TNF antibody, was experimentally tested in rats and it was found to significantly reduce the pathologic score and serum amylase activity and also to alleviate alveolar edema and acute respiratory distress syndrome; however, no studies are available in clinical human acute pancreatitis. Another substance, such as interleukin 10, was efficacious in decreasing the severity and mortality of lethal pancreatitis in rats, but seems to have no effect on human severe acute pancreatitis. Thus, the main problem in acute pancreatitis, especially in the severe form of the disease, is the difficulty of planning clinical studies capable of giving reliable statistically significant answers regarding the benefits of the various proposed therapeutic agents previously tested in experimental settings. According to the pathophysiology of acute pancreatitis, the efficacy of the drugs already available, such as gabexate mesilate, lexipafant and somatostatin should be re-evaluated and should be probably administered in a different manner. Of course, also in this case, we need adequate studies to test this hypothesis.

We report the imaging of a patient in whom the diagnosis of acute pancreatitis and the assessment of disease severity was carried out using echo-enhanced ultrasonography. Contrast-enhanced computed tomography confirmed the echo-enhanced ultrasonography picture. Echo-enhanced ultrasonography may become the imaging technique of choice in assessing the severity of acute pancreatitis since it is easy to perform, safe and lends itself to emergency situations. Most importantly, this technique should be also useful for following-up patients and it may be also an alternative to MRI in those patients in whom contrast-enhanced computed tomography cannot be carried out.

A patient with a history of radical thyroidectomy for medullary thyroid carcinoma (MTC) was studied by 68Ga [DOTA,1-Nal3]octreotide PET/CT for suspected relapse. PET/CT documented a focal area of somatostatin receptors expression at bone level. Although 68Ga DOTA-peptides PET has been successfully used for the detection of neuroendocrine tumors, its role in MTC patients is still under evaluation. In fact, although deriving from the neural crest, MTC cells may show a variable expression of somatostatin receptors. This case shows that PET/CT with DOTANOC may be a useful complementary imaging modality in patients with well-differentiated MTC.

In an era such as the present one in which there is a high demand for health services with the associated pressure of controlling spending, health care organizations are concerned about the cost-effectiveness of quality improvement interventions. On the other hand, the impact of the disease and the treatment on the patient's overall well-being and functioning has become a topic of growing interest not only in clinical research but also in practice. The clinical evaluation of the benefits of specific treatments for chronic, debilitating and incurable diseases should increasingly include formal assessment of patient activity and well-being. Thus, health-related quality of life as subjectively perceived by the patient, is becoming a major issue in the evaluation of any therapeutic intervention, mainly in patients with chronic or difficult diseases where the aim of the intervention is to keep patients either symptom-free and capable of living in the community for a long time or to reduce the discomfort caused by the disease. In this paper, we review the current knowledge on the quality of life assessment in chronic pancreatitis patients.