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Background. Non-alcoholic fatty liver disease (NAFLD) increases the risk of atherosclerosis but this risk may differ between metabolically- vs. genetically-driven NAFLD. High-density lipoprotein (HDL)-mediated cholesterol efflux (CEC) and plasma loading capacity (CLC) are key factors in atherogenesis. Aims. To test whether CEC and CLC differ between metabolically- vs. genetically-determined NAFLD. Methods: CEC and CLC were measured in 19 patients with metabolic NAFLD and wild-type PNPLA3 genotype (Group M), 10 patients with genetic NAFLD carrying M148M PNPLA3 genotype (Group G), and 10 controls PNPLA3 wild-types and without NAFLD. CEC and CLC were measured ex vivo by isotopic and fluorimetric techniques using cellular models. Results: Compared with Group G, Group M showed reduced total CEC (&minus, 18.6%, p &lt, 0.001) as well as that mediated by cholesterol transporters (&minus, 25.3% ABCA1, &minus, 16.3% ABCG1, 14.8% aqueous diffusion, all p &lt, 0.04). No difference in CEC was found between Group G and controls. The presence of metabolic syndrome further impaired ABCG1-mediated CEC in Group M. Group M had higher plasma-induced CLC than Group G and controls (p &lt, 0.001). Conclusions: Metabolically-, but not genetically-, driven NAFLD associates with dysfunctional HDL-meditated CEC and abnormal CLC. These data suggest that the mechanisms of anti-atherogenic protection in metabolic NAFLD are impaired.

Purpose. This multicenter randomized study was designed to compare the clinical and functional results of stapled transanal rectal resection (STARR) performed with 2 staplers (PPH-01 vs. PPH-03) in the treatment of hemorrhoidal disease associated with a large internal rectal prolapse. Methods. From a total of 937 patients, referred for hemorrhoidal disease in the 20 centers involved in the study, 425 (45.3%) with prolapsed hemorrhoids associated with a large internal rectal prolapse were randomized to undergo STARR with PPH-01 or PPH-03. Postoperative evaluation was made at 3, 6, and 12 months. Results. The incidence of bleeding at the stapled line was significantly lower in the PPH-03 group than in the PPH-01 group (58/207 [28.0%] vs. 145/201 [72.1%]; P < .0001); the mean number of hemostatic stitches was significantly higher in the PPH-01 than in the PPH-03 group (3.2 ± 0.1 vs. 1.8 ± 0.8; P < .0001). The mean operative time was 25.1 ± 11.5 minutes in the PPH-03 group and 38.1 ± 15.7 minutes in the PPH-01 group ( P < .0001). No major complications occurred in either of the groups. At 12-month follow-up, the success rate in the 2 groups was 94.5% in the PPH01 group and 94.2% in the PPH03 group. Conclusion. STARR performed for the treatment of hemorrhoidal disease associated with a large rectal prolapse is a safe and effective procedure. The use of the PPH-03 stapler instead of the PPH-01 guarantees a statistically significant reduction of intraoperative bleeding and a significant decrease of the operative time.

Malignant melanoma is characterized by metastases also to the gastrointestinal tract, especially in the small bowel. The diagnosis is often delayed because unspecific clinical presentation (frequently as chronic iron deficiency anemia, rectal bleeding or intestinal obstruction). We present a case of melanoma of unknown primary site, with clinical presentation of intestinal obstruction. A segmental resection of the ileum was performed including mesentery with lymph nodes. Histology revealed metastatic melanoma from unknown primary. PET and MRI confirmed disseminated disease without brain metastasis.

Malpractice is the responsible for the greatest number of legal claims. At the present time, legal actions against physicians in Italy are 15,000 per year, and a stunning increase about costs to refund patients injured by therapeutic and diagnostic errors is expected. The method for the medical prevention is “Risk Management”, that is the setting-up of organizational instruments, methods and actions that enable the measurement or estimation of medical risk; it allows to develop strategies to govern and reduce medical error. In the present work, the reconstruction about the history of risk management in Italy was carried out. After then the latest initiatives undertaken by Italy about the issue of risk management were examined.

Pelvic organ prolapse suspension (POPS) is a recent surgical procedure for one-stage treatment of multiorgan female pelvic prolapse. This study evaluates the preliminary results of laparoscopic POPS in 54 women with a mean age of 55.2 and a BMI of 28.3. Patients underwent at the same time stapled transanal rectal resection (STARR) to correct the residual rectal prolapse. We had no relapses and the preliminary results were excellent. We evaluated the patients after 1 year follow-up and we confirmed the validity of our treatment. The technique is simplier than traditional treatments with an important reduction or completely disappearance of the pre-operative symptomatology.

The posterior interosseous nerve palsy is a neuropathy of radial nerve interesting its deep motor branch. The neuropathy can appear with a hollow in the proximal half of the forearm without significant swelling, a complete loss of extension of the fingers with radial deviation of the wrist during extension. In some cases, PIN compression may simulate tendon rupture in rheumatologic diseases, because the pain and the paralysis occur suddenly, so often can be difficult to make a diagnosis. The palsy is caused by compression of the posterior interosseous nerve from soft tissue tumours or tumour-like masses: ganglions, lipomas, rheumatoid synovitis, synovial chondromatosis, fibromas, neurofibromas, bursitis, synovial cysts of the elbow and radioulnar proximal joints. The aim of our research was to individuate the better treatment for the posterior interosseous nerve palsy.From 2002 to 2007 we examined 8 patients: 2 female and 6 male. Median age was 43 years. The diagnosis was made by clinical examination, ultrasound, nerve conduction studies and magnetic resonance imaging (MRI). Patients underwent to decompressing posterior interosseous nerve surgery.After the surgical exploration in 8 cases a globular mass of around 2.5 cm to 4.5 cm diameter was discovered. At the histological examination, a synovial cyst of the elbow joint was found in 7 out of 8 patients and an hemangioma tumor in the one remaining patient. 12 months was the median time for a complete recovery after the operation, confirmed by EMG.The surgical treatment offers a complete resolution in all cases.

Splenic infarction is a rare cause of acute abdomen. It must be suspected in patient with hematologic diseases or thromboembolic conditions. The most common onset symptom is left-upper quadrant abdominal pain. Additional symptoms include fever and anemia. Laboratory may show elevated white blood cell and platelet counts.A 97-year-old female with a past history of atrial fibrillation presented with left-upper quadrant abdominal pain and fever since 20 days. Laboratory showed elevated white blood cell and platelet counts, increased C-reactive protein and lactate dehydrogenase. Both ultrasonographic and tomographic scans showed a large hypodense area of the spleen. The patient received intravenous antibiotic therapy, which led to significant clinical improvement with discharge 16 days after admission.The diagnosis of splenic infarction is based both on clinical presentation and imaging studies. Angio-computed tomography is the diagnostic procedure of choice. Ultrasonography and conventional radiology are useful in the differential diagnosis with other abdominal and thoracic diseases mimicking splenic infarction. In our case the management was conservative, because the patient was hemodynamically stable and antibiotic therapy could control the sepsis. Moreover, advanced age and poor cardiac and respiratory conditions contraindicated surgery.In our case splenic infarction was probably due to a thromboembolic event secondary to atrial fibrillation. In accordance with the literature, we suggest initial conservative therapy. Surgery is indicated only in the presence of complications.

Gallstone ileus is a rare complication of cholecystolithiasis. It causes 1-3% of the mechanical obstructions of the small bowel. It often affects patients between 63 and 85 years old. Pre-operative diagnosis is usually delayed 1-10 days because there is not a specific symptomatology.The authors report the case of a 50 year-old man with diagnosis of mechanical obstruction of the small bowel caused by a voluminous gallstone. Ileal occlusion was showed by CT. The patient underwent to one-stage emergency surgery with enterolithotomy, cholecystectomy and duodenal fistula repair. Patient's recovery was regular and he was discharged fourteen days after surgery.In our case gallstone ileus was diagnosed with a delay of 5 days. Ultrasonography was not able to show the gallbladder. Diagnosis was made by CT, which is the diagnostic gold standard.Patient's performance status influences surgical strategy. In our experience, the patient underwent one-stage surgery because he was considered at low risk. Instead staged procedure with enterolithotomy and delayed cholecystectomy and fistula repair, is performed only in patients at high risk.

High free tryptophan (F-TRP) plasma levels are found in cancer patients (CP). F-TRP plasma concentrations are affected by the levels of its carrier, albumin (ALB), and free fatty acids (FFA) competing with TRP for ALB binding sites. The lack of correlation between F-TRP, ALB and FFA in CP suggests a tumor-dependent effect on the rise in F-TRP. To verify this hypothesis, F-TRP, ALB and FFA levels were assayed in 12 lung and 16 breast CP susceptible to radical surgery, before and 15 days after surgical removal of the tumor. F-TRP levels significantly decreased after tumor ablation. Since no correlation was found between F-TRP, ALB and FFA variations, it is conceivable that the tumor itself may be responsible for the high F-TRP levels in CP.

Carcinosarcoma is a rare tumor of the uterus with a poor prognosis. We present a case of uterine carcinosarcoma in an 82-year-old woman who suffered from pervaginal bleeding for ten months duration with progressive anemia. Abdominopelvic nuclear magnetic resonance (NMR) imaging showed the presence of an intrauterine mass, infiltrating the myometrium and reaching the cervix. The patient was submitted to total abdominal hysterectomy with bilateral salpingo-oophorectomy. The carcinosarcoma, arising from the lumen of the uterus, infiltrated the inner one-third of the myometrial layer (pT1b, pNx, pMx; FIGO Stage 1B). A CT of the total body performed six months after surgery showed no signs of recurrent and/or metastatic tumor. The clinicopathological features, treatment options and prognosis of this aggressive neoplasm are reviewed.

To demonstrate the surgical treatment validity and the post-operative complication decrease.Seventythree women who underwent P.O.P.S. + S.T.A.R.R. treatment, follow-up one year.We observed an important reduction or a completely disappearance about pre-operative signs and symptoms.We are aware that the proposed technique, if taken into account by urogynecologists, will raise several arguments and will raise many doubts and perplexities. For this reason we wanted develop a follow-up sufficiently long and many case studies with data to support our claims.We believe that the procedure proposed by us, given the results, was excellent in patients with multiorgan pelvic prolapse, especially with the vagina walls elongated and that retain a good trophism.

Hepatocellular carcinoma (HCC) is an increasingly common form of cancer. Although its spontaneous rupture is rare in Western countries, it constitutes a surgical emergency and is associated with high mortality. There is a lack of consensus as to the best approach and what parameters to use in choosing it. The three main approaches are conservative, endovascular and resection - the treatment of choice for acute abdominal bleeding. We report a case of hemoperitoneum following the spontaneous rupture of an unrecognized HCV-related HCC in a patient with no history of liver disease. The patient was successfully treated by emergency surgery, with resection of two segments of the left liver.

Single Incision Laparoscopic Surgery (SILS) is a recent surgical technique, first described in the 1990s. Its aim is to optimize the esthetic result offered by laparoscopy by minimizing the number of abdominal incisions. Various preliminary studies have been carried out on the application of SILS, especially in cholecystectomy and appendectomy. This study evaluates the preliminary results of cholecystectomy by SILS (SILS™ Port) conducted between October 2009 and February 2011 on 21 patients (4 men and 17 women) with a mean age of 49.9 years and a mean Body Mass Index (BMI) of 22.8. All patients were treated by the same team, which had previously undergone six months' simulator training. There were two main selection criteria, both evaluated intraoperatively: absence of adhesions and of significant inflammatory sequelae from previous cholecystitis; and suitable distance between gallbladder and SILS access port. Conversion to traditional laparoscopy was necessary in just two cases, while an accessory trocar was introduced in another two cases. Conversion to open surgery was not necessary in any case. One case of SILS cholecystectomy was complicated by postoperative bile leakage, which was treated conservatively, as the fistula had a low output. The mean duration of hospitalization was 3.6 days. This preliminary experience led us to conclude that SILS is safe and highly satisfactory in the postoperative phase, thanks to the reduced need for painkillers and the improved esthetic result.

Abnormalities in lipid metabolism have been widely described in cancer-bearing patients and animals. In particular, the presence of the tumor seems to profoundly affect triglyceride (TG) utilization by interfering with lipoprotein lipase (LPL) activity. Exogenous TG plasma clearance was evaluated in 10 nonmalnourished patients with cancers of various origin and 10 normolipidemic volunteers by means of a three-stage intravenous lipid clearance test. This technique allows precise determination of both the fractional removal rate (K2) and the maximal clearing capacity (K1) for exogenous lipids. Mean K2 values (min-1) were found to be significantly reduced in cancer patients compared with control subjects (0.07 +/- 0.006 vs 0.13 +/- 0.013 SEM, p less than 0.005). K1 values (mumol/L/min) were also found to be significantly lower in cancer patients than in the control group (109.43 +/- 6.3 vs 143 +/- 6.3 SEM, p less than 0.01). The data obtained indicate that the capacity to eliminate exogenous lipids from the bloodstream is reduced in cancer-bearing patients. This may be the consequence of a tumor-related impairment of LPL system activity.

Renal Cell Carcinoma (RCC) is generally characterized by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT in correctly identifying RCC lung metastases using histology as the standard of truth. The records of 350 patients affected by RCC were retrospectively analyzed. The inclusion criteria were: (a) biopsy- or histologically proven RCC; (b) Computed Tomography (CT) evidence of at least one lung nodule; (c) [18F]FDG-PET/CT performed prior to lung surgery; (d) lung surgery with histological analysis of surgical specimens; (e) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as the standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57 cases (53.3%), while 50 lesions (46.7%) were related to other lung malignancies. Applying a cut-off of SUVmax ≥ 2, the sensitivity and the specificity of [18F]FDG-PET/CT in detecting RCC lung metastases were 33.3% (95% CI: 21.4–47.1%) and 26% (95%CI: 14.6–40.3%), respectively. Although the analysis demonstrated a suboptimal diagnostic accuracy of [18F]FDG-PET/CT in discriminating between lung metastases from RCC and other malignancies, a semiquantitative analysis that also includes volumetric parameters (MTV and TLG) could support the correct interpretation of [18F]FDG-PET/CT images.

PURPOSE: To perform an external validation of a recently published nomogram aimed to predict positive 68Ga-PSMA-11 PET/CT in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) by Rauscher et al. (Eur Urol 73(5):656-661, 2018). METHODS: Overall, 413 PCa patients with BCR after RP (two consecutive PSA ≥ 0.2 ng/ml) and PSA value between 0.2 and 1 ng/ml were included. A multivariable logistic regression model was produced to assess the predictors of positive 68Ga-PSMA-11 PET/CT results. The performance characteristics of the model were assessed by quantifying the predictive accuracy, according to model calibration. Yuden's index was used to find the best nomogram's cut-off. Finally, decision curve analysis (DCA) was implemented to quantify the nomogram's clinical value. RESULTS: In the external cohort, the overall detection rate of 68Ga-PSMA-11 PET/CT was 44% vs. 64.7% in the original population. At multivariate analysis, PSA at 68Ga-PSMA-11 PET/CT (OR: 7.06, p 35%. CONCLUSION: We assessed similar suboptimal predictive accuracies in the external cohort compared to the original one. PSA and ongoing ADT were confirmed as positive predictors, and the most informative nomogram cut-off resulted 35%.

Rationale The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions. Methods A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process. Results According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET. Conclusions The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.

OBJECTIVE: To evaluate the clinical impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography on the planned management of prostate cancer patients with biochemical recurrence after surgery. METHODS: We enrolled 276 prostate cancer patients referred to 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography due to biochemical recurrence after surgery (two consecutive prostate-specific antigen assays ≥0.2 ng/mL). First, the detection rate of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was assessed according to different prostate-specific antigen levels. Second, the independent predictors of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography positive results were assessed. Finally, the intended treatment before revision of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was assessed by a multidisciplinary team based on the European Association of Urology guidelines, patient clinical condition and clinical parameters. Then, re-assessment of the treatment plan was prospectively recorded by the same board after revision of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography. The effective clinical impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was rated as major (change in therapeutic approach), minor (same treatment, but modified therapeutic strategy) or none. RESULTS: The overall detection rate of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography was 47.5%. Prostate-specific antigen at 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (odds ratio 3.52) and prostate-specific antigen doubling time 2 ng/mL, respectively. CONCLUSIONS: 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography allows clinicians to radically change the intended treatment approach before imaging evaluation, in roughly two out three individuals.

Introduction This is a prospective, single-center trial in pediatric patients with sarcoma aiming to evaluate [18F]FDG PET/CT as a tool for early response assessment to neoadjuvant chemotherapy (neo-CTX). Methods Bone or soft tissue sarcoma patients with (1) baseline [18F]FDG PET/CT within 4 weeks prior to the start of neo-CTX (PET1), (2) early interim [18F]FDG PET/CT (6 weeks after the start of neo-CTX (PET2), (3) evaluation of neo-CTX response by histology or MRI, and (4) definitive therapy after neo-CTX (surgery or radiation) were included. Semiquantitative PET parameters (SUVmax, SUVmean, SUVpeak, MTV and TLG) and their changes from PET1 to PET2 (ΔPET) were obtained. The primary endpoint was to evaluate the predictive value of PET1, PET2 and ΔPET parameters for overall survival (OS) and time to progression (TTP). The secondary outcome was to evaluate if [18F]FDG PET/CT can predict the response to neo-CTX assessed by histopathology or MRI. Primary and secondary outcomes were also evaluated in a subpopulation of patients with bone involvement only. Results Thirty-four consecutive patients were enrolled (10 females; 24 males; median age 15.1 years). 17/34 patients (50%) had osteosarcoma, 13/34 (38%) Ewing's sarcoma, 2/34 (6%) synovial sarcoma and 2/34 (6%) embryonal liver sarcoma. Median follow-up was 39 months (range 16–84). Eight of 34 patients (24%) died, 9/34 (27%) were alive with disease, and 17/34 (50%) had no evidence of residual/recurrent disease. Fifteen of 34 (44%) and 19/34 (56%) were responders and non-responders, respectively. PET2-parameters were associated with longer TTP (p p = 0.047). None of the PET1, PET2 or ΔPET parameters were associated with OS. Conclusion [18F]FDG PET/CT performed 6 weeks after the start of neo-CTX can serve as an early interim biomarker for TTP and pathologic response but not for OS in pediatric patients with sarcoma.

Context Optimal management of prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy and pelvic lymph node dissection still remains unclear. Objective To assess the effectiveness of postoperative treatment strategies for pathologically node-positive PCa patients. The secondary aim was to identify the most relevant prognostic factors to guide the management of pN1 patients. Evidence acquisition A systematic review was performed in January 2020 using Medline, Embase, and other databases. A total of 5063 articles were screened, and 26 studies including 12 537 men were selected for data synthesis and included in the current review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Evidence synthesis Ten-year biochemical recurrence (BCR)-free, clinical recurrence–free, cancer-specific (CSS), and overall (OS) survival rates ranged from 28% to 56%, 70% to 92%, 72% to 98%, and 60% to 87.6%, respectively. A total of seven, five, and six studies assessed the oncological outcomes of observation, adjuvant radiotherapy (aRT), or adjuvant androgen deprivation therapy (ADT), respectively. Initial observation followed by salvage therapies at the time of recurrence represents a safe option in selected patients with a low disease burden. The use of aRT with or without ADT might improve survival in men with locally advanced disease and a higher number of positive nodes. Risk stratification according to pathological Gleason score, number of positive nodes, pathological stage, and surgical margins status is the key to risk stratification and selection of the optimal postoperative therapy. Limitations of this systematic review are the retrospective design of the studies included and the lack of data on adverse events. Conclusions While the majority of men with pN1 disease would experience BCR after surgery, long-term disease-free survival has been reported in selected patients. Management options to improve oncological outcomes include observation versus adjuvant therapies such as aRT and/or ADT. Disease characteristics should be used to select the optimal postoperative management for pN1 PCa patients. Patient summary Finding node-positive prostate cancer after a radical prostatectomy often leads to high postoperative prostate-specific antigen levels and is overall a poor prognostic factor. However, this does not necessarily translate into poor survival for all men. Management can be tailored to the severity of disease and options include observation, androgen deprivation therapy, and/or radiotherapy.

This article reviews the role of 11C-choline-PET/computed tomography (CT) in patients with prostate cancer for diagnosis, staging, and restaging the disease in case of biochemical recurrence after primary treatment. The main application of this imaging procedure is restaging of the disease in case of biochemical recurrence. 11C-Choline-PET/CT proved its value for metastases-directed salvage therapies and for monitoring therapy response in castration-resistant patients. Prostate-specific antigen and prostate-specific antigen kinetics values confirmed their correlation with 11C-choline PET/CT sensitivity.11C-CholinePET/CT, despite low sensitivity to stage disease or in case of biochemical failure with low PSA levels, has an important impact on the management of patients with prostate cancer.

Korrespondenz zu 10.1016/S1470-2045(19)30586-8

Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate-specific membrane antigen (PSMA) PET/CT detects PCa metastasis with superior accuracy, having a potential impact on the planning of definitive radiation therapy (RT) for nonmetastatic PCa. Our objectives were to determine how often definitive RT planning based on standard target volumes covers 68Ga-PSMA-11 PET/CT-defined disease and to assess the potential impact of 68Ga-PSMA-11 PET/CT on definitive RT planning. Methods: This was a post hoc analysis of an intention-totreat population of 73 patients with localized PCa without prior local therapy who underwent 68Ga-PSMA PET/CT for initial staging as part of an investigational new drug trial. Eleven of the 73 were intermediate- risk (15%), 33 were high-risk (45%), 22 were very-highrisk (30%), and 7 were N1 (9.5%). Clinical target volumes (CTVs), which included the prostate, seminal vesicles, and (in accord with the Radiation Therapy Oncology Group consensus guidelines) pelvic lymph nodes (LNs), were contoured on the CT portion of the PET/CT images by a radiation oncologist masked to the PET findings. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had one or more 68Ga-PSMA-11-positive primary prostate lesions. Twenty-five (34%) and 7 (9.5%) of the 73 patients had 68Ga-PSMA- 11-positive pelvic LN and distant metastases, respectively. The sites of LN metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper diaphragm (4%), and presacral (1.5%). The median size of the LN lesions was 6 mm (range, 4-24 mm). RT planning based on the CTVs covered 69 (94.5%) of the 73 primary lesions and 20 (80%) of the 25 pelvic LN lesions, on a per-patient analysis. Conclusion: 68Ga-PSMA-11 PET/CT had a major impact on intended definitive RT planning for PCa in 12 (16.5%) of the 73 patients whose RT fields covered the prostate, seminal vesicles, and pelvic LNs and in 25 (37%) of the 66 patients whose RT fields covered the prostate and seminal vesicles but not the pelvic LNs.

Grade 3 (G3) neuroendocrine tumors (NETs) are a novel category among digestive neuroendocrine neoplasms, characterized by Ki-67 >20% and a well-differentiated morphology, presenting high intra-tumor heterogeneity. We aimed to explore the role of dual-tracer PET imaging (68Gallium (Ga)-DOTATOC and 18Fluorodeoxyglucose (FDG)) as overall survival (OS) predictor in NET G3 patients. We performed a retrospective analysis in NET G3 patients treated at our institution between 2003 and 2021. Accordingly, 30 NET G3 patients were analyzed. 68Ga-DOTA-TOC and 18F-FDG uptake were assessed by tumor/non-tumor (T-nonT) ratio. We reported a slightly better OS for patients with ≥75% concordance between 68Ga-DOTA-TOC and 18F-FDG PET/CT (p = 0.42). Among patients with discordant functional imaging, we reported a better 5-y OS rate for patients with a prevalent 68Ga-DOTATOC vs. 18F-FDG PET/CT (p = 0.016). In positive 18F-FDG PET/CT cases, we reported a better OS for p = 0.021). Among upfront-NET G3 patients with concordant exams, 5-y OS rate was 83.3% (95% CI: 27.3–97.5). Among patients with discordant exams, 5-y OS rate was 81.3% (52.5–93.5), 100% for those with prevalent receptor expression, and 50% (11.1–80.4) for those with prevalent 18F-FDG uptake. Our findings suggest that dual-tracer PET/CT can be considered as a predictor of patient outcome, able to stratify NET G3 patients with poorer prognosis.

Aim: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. Materials and methods: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). Results: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). Conclusion: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

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METHODS: After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers (68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement [Krippendorff's (K) alpha

The aim of this study was to investigate the diagnostic accuracy of 18F-FDG-PET/CT in osteosarcoma patients suspicious for disease recurrence after adequate surgical therapy. Inclusion criteria were: a) adequate surgical treatment for proven osteosarcoma and documented complete remission after therapy; b) 18F-FDG-PET/CT performed during follow-up for clinical/diagnostic suspicion of relapse; c) new surgical treatment with excision of the suspected lesions; d) histological validation of 18F-FDG-PET/CT findings. Thirty-seven patients matching all inclusion criteria were retrospectively enrolled (20 men and 17 female). Primary surgical treatment consists of resection (31 cases) or amputation (six cases). 18F-FDG-PET/CT performance was assessed with a per-patient and per-site evaluation of sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV). The sites of relapse were classified as local, lung, lymphnodes (LNs), and distant (other skeletal segments and/or distant soft tissue). The disease-free survival (DFS) and the overall survival (OS) after 18F-FDG PET/CT were evaluated. 18F-FDG-PET/CT was positive in 89.2% (33/37) of patients. Local uptake only was observed in 35.1% patients (13/37); lung uptake only in 18.9% (7/37); distant uptake only in 2.7% (1/37) case; multiple sites of uptake in 32.4% (12/37). Histology resulted positive in 92% (34/37) of patients. A total of 51 pathologic lesions were evaluated (22 local relapse, 11 lung metastasis, 10 metastatic LNs, eight distant metastatic lesions). On a per-patient analysis 18F-FDG-PET/CT showed a sensitivity, specificity, accuracy, PPV, and NPV of 91%, 75%, 89%, 97%, 50%. On a per-site analysis the performance for local relapse was 96%, 100%, 97%, 100%, 93%, while for lung relapse detection was 80%, 100%, 92%, 100%, 88%. The mean follow-up after 18F-FDG-PET/CT was 21.5 months. At the last follow-up, 19% (7/37) of patients were death with disease, 38% (14/37) were alive with disease, and 43% (16/37) had no evidence of disease. Overall survival was 90% and 75% at 24 and 60 months, respectively. 18F-FDG-PET/CT showed valuable results for detecting recurrence(s) in osteosarcoma patients with suspicious of relapse after treatment, particularly in the detection of local relapse and lung metastasis.

In this issue of the European Journal of Nuclear Medicine, Castello et al. [1] performed a retrospective analysis in 168 metastatic castration-resistant prostate cancer (mCRPC) patients who underwent 223RaCl2. All patients presented bone metastases and 34% of these patients had concomitant visceral and/or nodal metastases. Authors evaluated the prognostic impact of PSA flare on overall survival (OS) and progression-free survival (PFS) in this cohort. This is the first study specifically designed to assess the presence and the influence of PSA flare in patients undergoing alpha-emitting radiopharmaceuticals. The PSA flare is a well-known phenomenon observed in several studies in the course of systemic therapies, including hormonal therapies (especially luteinizing hormone-releasing hormone (LHRH) agonist), new androgen receptor targeted therapies (abiraterone acetate or enzalutamide) and taxane-based chemotherapy (either docetaxel or cabazitaxel) [2]. A transient PSA rise followed by a decrease of PSA below the baseline can be considered a temporary flare-up. The cause of such flare has only been postulated. Many suggest that it could be caused by PSA release from lysed cells. However, the aberrant activation of the androgen receptor or the transactivation of the androgen receptor induced by corticosteroids have been suggested as the possible cause responsible for PSA flare-up during systemic therapy [3]. Other explanations are related to cellular heterogeneity and diversity in terms of drug sensitivity, cell cycle kinetics, and PSA expression [4]. The development of PSA flare does not influence disease-specific outcomes. Its incidence is attested in 5–30% of patients receiving LHRH agonist and in 8–20% of patients receiving chemotherapy [2, 5]. As treatment of mCRPC becomes more complex, and definitions of progression on treatment continue to evolve, referring physicians must be aware of this laboratory pattern to avoid unnecessary discontinuation of these therapies based on early PSA change alone. Castello et al. [1] confirmed the presence of PSA flare-up also in mCRPC patients treated with alpha-emitting radiopharmaceuticals (223RaCl2). Although there is no agreed definition on the extent of the following PSA decline to be considered as a flare after an initial rise in PSA, a flare followed by a decrease below the baseline is generally considered the most accepted definition. According to these criteria, authors observed PSA flare-up in 11.9% of their population. In the flare group, OS and PFS were considerably better than in the non-responder group. These results are consistent with data obtained in mCRPC patients undergoing abiraterone or taxane-based chemotherapies [2, 3, 5, 6]. 233RaCl2 preferentially targets new bone growth surrounding bone metastases while emitting alpha particles within the tumour microenvironment. Whereas beta particles generate primarily single-stranded deoxyribonucleic acid breaks that may be overcome by cellular repair mechanisms, alpha particles have high linear energy transfer with enhanced ability to induce lethal double-stranded deoxyribonucleic acid breaks, thus eliciting greater cytotoxic effects on bone-metastatic tumour sites [7]. Accordingly, Castello et al. hypothesized that PSA flare during 233RaCl2 treatment is due to PSA release from tumour cell lysis, and may correspond to a high degree of tumour cell death. However, the concomitant administration of therapies, including hormonal therapy, can be responsible for the PSA flare-up in this patient-series, through the activation of the androgen receptor. Nevertheless, regardless of the mechanisms involved, 233RaCl2 therapy should not be discontinued after an early and transient PSA rise. The PSA flare induced by alpha-emitting therapy during, at least, the first 2 months of treatment (one to two cycles), does not represent a proven sign of disease progression. Since the introduction of PSA screening, prostate cancer diagnosis and management have been guided by this biomarker based on the assumption that PSA levels have been shown to be associated with disease burden [8]. However, this correlation becomes more complicated in advanced disease states that are characterized by increasing disease cells heterogeneity, due to the complex mechanisms involved in the development of castration-resistant prostate cancer [9]. Furthermore, recent studies have described the presence of active visceral metastases not producing PSA [10]. For these reasons, the Prostate Cancer Clinical Trial Working Group 3 (PCWG3) suggest also using other blood-based markers (e.g., alkaline phosphatase, lactate dehydrogenase, and circulating tumour cells) to follow up patients treated with systemic treatment [11]. At present, the usefulness of imaging for monitoring the response to therapy in mCRPC patients is being debated [12]. Bone scan (either sodium-fluoride PET or bone scintigraphy) is widely used in clinical practice, and has been proposed in some studies [13] for predicting the response to bone-targeted therapy, especially alpha-emitting radiopharmaceuticals. However, this imaging modality evaluates only the skeletal involvement by prostate cancer metastases. Thus, the eventual progression of the disease in other sites cannot be assessed. Furthermore, its efficacy is impaired by the bone scan flare phenomenon (the development of new lesions on a first follow-up scan that may actually do not represent disease progression). Recently, highly successful results have been obtained targeting the prostate specific membrane antigen (PSMA), both for diagnostic and therapeutic purposes. PSMA-11 PET/CT outperformed choline PET/CT in patients presenting PSA failure after radical therapy [14], but its role in later stages has not been extensively validated. On the other hand, in advanced stages of the disease the use of PSMA-ligands as therapeutic agent is gaining importance. Radionuclide treatment with 177Lu-PSMA-617 has high response rates, low toxic effects, and reduction of pain in men with mCRPC who have progressed after conventional treatments [15]. Thus, PSMA may represent the ideal in-vivo biomarker for theranostic purposes in prostate cancer. At present, the incidence of PSA flare in patients treated with PSMA-based radioligand therapy (either with beta or alpha emitters) has not been reported in large patient-series. However, the presence of this phenomenon is largely predictable also in those patients treated with this innovative therapy. PCWG3 suggest that early PSA rise should be ignored before 12 weeks of treatment in determining PSA response [11]. Accordingly, there is an unmet need to assess the early response to therapy in order to minimize patient exposure to ineffective therapy. The availability of a diagnostic procedure able to assess the response to therapy accurately and at an early stage may have an important impact on mCRPC management. Although PSMA PET/CT cannot completely replace bone scan for detecting active osteoblastic lesions in patients treated with alpha-emitting radiopharmaceuticals, PSMA PET/CT may help with better treatment planning. Patients with undetected nodal or visceral metastases or bone-marrow involvement should be restaged and addressed to the most tailored treatment strategy. In addition to this approach providing an improvement in life expectancy, the collateral effects, toxicity, and costs of futile therapy will be reduced. In conclusion, the presence of PSA flare has been described also in mCRPC patients treated with 223RaCl2 [1]. Considering the heterogeneity of PSA expression in advanced prostate cancer, this biomarker is less reliable in advanced stages of the disease. The role of PSMA PET imaging in this scenario has not been extensively explored, but deserves more attention in the light of the increasing interest of this radiopharmaceuticals as a therapeutic agent.

Background The terms "Hernia Center" (HC) and Hernia Surgeon" (HS) have gained more and more popularity in recent years. Nevertheless, there is lack of protocols and methods for certification of their activities and results. The Italian Society of Hernia and Abdominal Wall Surgery proposes a method for different levels of certification. Methods The national board created a commission, with the task to define principles and structure of an accreditation program. The discussion of each topic was preceded by a Systematic Review, according to PRISMA Guidelines and Methodology. In case of lack or inadequate data from literature, the parameter was fixed trough a Commission discussion. Results The Commission defined a certification process including: "FLC - First level Certification": restricted to single surgeon, it is given under request and proof of a formal completion of the learning curve process for the basic procedures and an adequate year volume of operations. "Second level certification": Referral Center for Abdominal Wall Surgery. It is a public or private structure run by at least two already certified and confirmed FLC surgeons. "Third level certification": High Specialization Center for Abdominal Wall Surgery. It is a public or private structure, already confirmed as Referral Centers, run by at least three surgeons (two certified and confirmed with FLC and one research fellow in abdominal wall surgery). Both levels of certification have to meet the Surgical Requirements and facilities criteria fixed by the Commission. Conclusion The creation of different types of Hernia Centers is directed to create two different entities offering the same surgical quality with separate mission: the Referral Center being more dedicated to clinical and surgical activity and High Specialization Centers being more directed to scientific tasks.

The aim of the study was to assess which factors may influence (11)C-choline PET/CT detection rate in a population of recurrent prostate cancer (PCa) patients listed for salvage radiation therapy (S-RT) in an early phase of biochemical relapse, to select which patients could obtain the most benefit by performing restaging (11)C-choline PET/CT before S-RT. METHODS: The study comprised 605 patients, treated with radical prostatectomy (RP) with curative intent for PCa who showed rising PSA levels after primary therapy and listed for S-RT. Prostate-specific antigen (PSA) values were >0.2 ng/mL and

AIM: The aim of our retrospective study was to assess the usefulness of F-FDG PET/CT in the restaging of clear cell renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: Sixty-nine patients (median age = 62 years; range = 36-86 years) affected by clear cell RCC (TNM at staging: T1, 42 patients; T2, 13 patients; T3, 11 patients; T4, 3 patients; Fuhrman grade: G2, 47 patients; G3, 20 patients; G4, 2 patients) underwent whole-body F-FDG PET/CT to restage the disease after nephrectomy for clinical or radiological suspicion of metastases. Areas of abnormal uptake at PET/CT were classified, taking the liver uptake as reference, as follows: 1 = faint uptake, lower than liver; 2 = moderate uptake, equal to liver; and 3 = high uptake, higher than liver. Validation of F-FDG PET/CT results was established by (1) biopsy (23 patients) and (2) other imaging modalities (addressed BS; c.e.CT; MRI; F-fluoride PET/CT; subsequent F-FDG PET/CT), and/or clinical and radiological follow-up of 12 months (46 patients). RESULTS: F-FDG PET/CT was positive in 42 patients and negative in 27 patients. Sixteen patients presented single lesions and 26 patients presented multiple localizations of the disease. On a patient basis, 40 patients resulted true positive, 2 patient false positive, 23 patients true negative, and 4 patients false negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 90%, 92%, 91%, 95%, and 85%, respectively. On a lesion basis, PET/CT detected 114 areas of abnormal uptake in 42 positive patients of which 112 resulted to be true positive. FDG uptake of the true positive lesions resulted to be high in 83 cases, moderate in 17 lesions, and finally faint in 12 lesions. CONCLUSIONS: F-FDG PET/CT demonstrated a good sensitivity in the restaging of clear cell RCC. Most of the lesions showed intense activity. According to our results, it seems that the use of F-FDG PET/CT in the restaging of RCC is feasible because the number of false-negative cases is limited.

AIM: The aim of this study was to evaluate the role of C-choline PET/CT in the preoperative evaluation of the nodal involvement of patients with bladder carcinoma (BC) suitable for radical cystectomy and extended pelvic lymph node dissection in comparison with contrast-enhanced CT (CECT) using the pathologic specimen as reference standard. PATIENTS AND METHODS: Twenty-six consecutive patients (69.5 ± 9.3 years; range, 49-84) with histologically proven transitional cell BC were treated with radical cystectomy and pelvic lymph node dissection and were enrolled from April 2011 to January 2013. In all patients, paravesical, internal, eternal, and common iliac nodes as well as obturatory, presacral, preaortic, and precaval lymph nodes (LNs) were dissected up to the origin of the inferior mesentery artery. The areas of the LN dissection were grouped as follow: region A included preaortic and precaval LNs; region B included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the right pelvis; region C included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the left pelvis. C-choline PET/CT and abdominal CECT were used to assess the presence of lymph node metastases on a per patient, region, and lesion analysis using the results of surgical specimens obtained at operation as criterion standard. RESULTS: Seven of 26 patients (26.9%) showed nodal metastases at pathologic analysis. Overall, 844 LNs were evaluated, and 38 of them (4.5%) showed metastatic involvement. On a patient-based analysis, C-choline PET/CT showed a sensitivity of 42% and specificity of 84%, whereas, CECT showed a sensitivity of 14% and specificity of 89%. On a region-based analysis, C-choline PET/CT showed a sensitivity of 11% and specificity of 82%, whereas CECT showed a sensitivity of 5% and specificity of 80%. On a lesion (LN)-based analysis, C-choline PET/CT showed a sensitivity of 10% and specificity of 64%, whereas CECT showed a sensitivity of 2% and specificity of 63%. CONCLUSIONS: C-choline PET/CT could provide additional diagnostic information in preoperative nodal staging of patients with invasive BC in comparison with CECT. A study with a larger population should determine if C-choline PET/CT could be recommended as a routine technique in high-risk patients with BC

About 40% of all patients undergoing radical treatment for localized prostate cancer (PCa) develop biochemical relapse (BCR) during lifetime but only 10-20% of them will show clinically detectable recurrences. Prostatic bed, pelvic or retroperitoneal lymph nodes (LN) and bones (especially the spine) are the sites where we must focus our attention in the early phase of PSA relapse. Time to PSA relapse, PSA kinetics, pathological Gleason score and pathological stage are the main factors related to the likelihood of local vs. distant relapse. Before an extensive diagnostic work-up in patients with BCR, is mandatory to understand if there is a therapeutic consequence or not for the patient. Current imaging techniques have some potential but many limits are yet encountered in the diagnosis of disease relapse. Transrectal ultrasound (TRUS) and Multiparametric Magnetic Resonance Imaging (MRI) have low accuracy in the detection of the recurrence. Today, Choline PET/CT may visualize the site of recurrence earlier, with better accuracy than conventional imaging, in a single step and even in the presence of low PSA level. In recent years, the new radiotracer (18)F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect PCa relapse. From a clinical point of view, first clinical studies showed very promising and reproducible results with an improvement in sensitivity is about 20-25% with respect to Choline PET/CT, rendering the FACBC the possible radiotracer of the future for PCa. In conclusion, many improvements have been recently achieved in imaging techniques for PCa restaging, essentially in Nuclear Medicine and MRI, but negative results remain in many cases. Low sensitivity, costs, availability of technologies and confirmation of the results remain the major limitations in most cases.

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.

PURPOSE: To investigate the role of 11C-choline PET/CT for evaluating the response to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with docetaxel in comparison with PSA response. METHODS: Inclusion criteria were (a) proven mCRPC, (b) docetaxel as first line of chemotherapy (docetaxel 75 mg/m2 + prednisone 5 mg), and (c) 11C-choline PET/CT and PSA values assessed before and after docetaxel administration. A total of 61 patients were retrospectively enrolled (mean age 68.9 years, range 57 - 84 years). 11C-Choline PET/CT was performed at baseline before docetaxel treatment (PET1) and after the end of treatment (PET2). PSA values were measured before treatment (PSA1) and after treatment (PSA2). PET2 was reported as complete response (CR), partial response (PR) or stable disease (SD). Progressive disease (PD) was considered if a new lesion was seen. PSA trend was calculated from the change in absolute values between PSA1 and PSA2. A decrease of ≥50 % between PSA1 and PSA2 was considered a PSA response. Clinical, radiological and laboratory follow-up ranged from 6 to 53 months (mean 13.5 months). RESULTS: Of the 61 patients, 40 (65.5 %) showed PD on PET2, 13 (21.3 %) showed SD, 2 (3.4 %) showed PR, and 6 (9.8 %) showed CR. An increasing PSA trend was seen in 29 patients (47.5 %) and a decreasing PSA trend in 32 patients (52.5 %). A PSA response of ≥50 % was seen in 25 patients (41 %). Radiological PD was seen in 23 of the 29 patients (79.3 %) with an increasing PSA trend, in 16 of the 32 patients (50 %) with a decreasing PSA trend, and in 11 of the 25 patients (44 %) with a PSA response of ≥50 %. In the multivariate statistical analysis, the presence of more than ten bone lesions detected on PET1 was significantly associated with an increased probability of PD on PET2. No association was observed between PSA level and PD on PET2. CONCLUSION: Our results suggest that an increasing PSA trend measured after docetaxel treatment could be considered predictive of PD. In patients with decreasing PSA values (decreasing PSA trend and a PSA response of ≥50 %), 11C-choline PET/CT may be useful to identify those with radiological progression despite a PSA response. Finally, the tumour burden, expressed as number of bone lesions on PET1, is significantly associated with an increased probability of PD on PET2.

AIM: The aim of this study was to compare C-choline PET/CT, prostate-specific antigen (PSA), PSA kinetics, and C-choline uptake in recurrent metastatic prostate cancer patients with osteoblastic and osteolytic bone metastases. PATIENTS AND METHODS: We retrospectively analyzed 140 patients with the following criteria: (a) positive bone lesions identified with C-choline PET/CT and validated as true positive by histology (14.2%), correlative imaging (33.4%), or clinical follow-up (52.4%); (b) after radical prostatectomy (67.9%) or primary radiotherapy (22.1%); (c) proven biochemical relapse with rising PSA levels; (d) no chemotherapy, zoledronic acid, or palliative bone external beam radiation therapy previously administrated during biochemical relapse; and (f) asymptomatic for bone pain. Lesions were categorized as osteoblastic, osteolytic, or bone marrow lesions. Patients were divided into osteoblastic and osteolytic patient groups. RESULTS: C-Choline PET/CT detected oligometastatic bone disease (1-3 lesions) in 98 (70%) of the 140 patients and multiple bone lesions in 42 (30%) of the 140 patients. By per-lesion analysis of 304 lesions, there were 184 osteoblastic, 99 osteolytic, and 21 bone marrow lesions.By per-patient analysis, 97 (69.3%) of the 140 patients were in the osteoblastic group, whereas 43 (30.7%) of the 140 patients were in the osteolytic group. Statistically significant differences in SUVmax (P < 0.001), fast PSA doubling time (P = 0.01), and PSA velocity (P = 0.01) were observed between osteoblastic (lower values) and osteolytic (higher values) groups. By multivariate analysis, fast PSA doubling time was a significant predictor for osteolytic lesions. CONCLUSIONS: We demonstrated differences in PSA kinetics and SUVmax between osteolytic and osteoblastic lesions. C-Choline PET/CT may identify patients that could benefit from early targeted therapies, depending on the type of bone lesions expressed.

PURPOSE: The aim of this retrospective two-centre study was to investigate the clinical impact of 11C-choline PET/CT on treatment management decisions in patients with recurrent prostate cancer (rPCa) after radical therapy. METHODS: Enrolled in this retrospective study were 150 patients (95 from Bologna, 55 from Würzburg) with rPCa and biochemical relapse (PSA mean ± SD 4.3 ± 5.5 ng/mL, range 0.2-39.4 ng/mL) after radical therapy. The intended treatment before PET/CT was salvage radiotherapy of the prostatic bed in 95 patients and palliative androgen deprivation therapy (ADT) in 55 patients. The effective clinical impact of 11C-choline PET/CT was rated as major (change in therapeutic approach), minor (same treatment, but modified therapeutic strategy) or none. Multivariate binary logistic regression analysis included PSA level, PSA kinetics, ongoing ADT, Gleason score, TNM, age and time to relapse. RESULTS: Changes in therapy after 11C-choline PET/CT were implemented in 70 of the 150 patients (46.7 %). A major clinical impact was observed in 27 patients (18 %) and a minor clinical impact in 43 (28.7 %). 11C-choline PET/CT was positive in 109 patients (72.7 %) detecting local relapse (prostate bed and/or iliac lymph nodes and/or pararectal lymph nodes) in 64 patients (42.7 %). Distant relapse (paraaortic and/or retroperitoneal lymph nodes and/or bone lesions) was seen in 31 patients (20.7 %), and both local and distant relapse in 14 (9.3 %). A significant difference was observed in PSA level and PSA kinetics between PET-positive and PET-negative patients (p 0.05). In both centres the same criteria to validate PET-positive findings were used: in 17.3 % of patients by histology and in 82.7 % of patients by correlative imaging and/or clinical follow-up (follow-up mean 20.5 months, median 18.3 months, range 6.2-60 months). CONCLUSION: 11C-Choline PET/CT had a significant impact on therapeutic management in rPCa patients. It led to an overall change in 46.7 % of patients, with a major clinical change implemented in 18 % of patients. Further prospective studies are needed to evaluate the effect of such treatment changes on patient survival.