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Purpose: Gastroenteropancreatic -neuroendocrine tumours (GEP-NETs) are commonly treated with surgical resection or long-term therapies for tumour growth control. Lutetium [177Lu]-DOTA-TATE was approved for the treatment of GEP-NETs after the phase III NETTER 1trial demonstrated improved progression free survival, objective response rates and health-related quality of life (HRQoL) compared to high-dose somatostatin analogues. No real-world data exist on prescribing habits and clinically significant endpoints for [177Lu]Lu-DOTA-TATE treatment in Italy. REAL-LU is a multicentre, long-term observational study in patients with unresectable/metastatic GEP-NETs progressing on standard therapies in Italian clinical practice. A pre-specified interim analysis was performed at the end of the enrolment period, data from which are described herein. Methods: Overall duration of REAL-LU will be approximately 48 months, with 12- and 36-month recruitment and follow-up periods, respectively. The primary objective is to evaluate [177Lu]Lu-DOTA-TATE effectiveness in terms of progression-free survival. Secondary objectives include safety, impact on HRQoL, and identification of prognostic factors. This pre-specified interim analysis describes patient profiles, at the end of enrollment, of those prescribed [177Lu]Lu-DOTA-TATE for GEP-NETs in Italy. Results: Among 161 evaluable patients, mean age was 64.7 ± 10.3 years at study entry, 83.8% presented with no clinical signs of disease at physical examination, and most had minor disease symptoms. All patients had metastatic disease, most commonly in the liver (83.9%) with a median of two metastatic sites. In 90.7% of patients, the disease was stage IV, and 68.3% had ≥ 1 target lesion. [177Lu]Lu-DOTA-TATE was prescribed mainly as second-line therapy (61.6%) and following surgery (58.4%). HRQoL assessments revealed high levels of functioning and low levels of symptoms at baseline; 50.0% of patients were symptom-free at study entry. Conclusion: The characteristics of patients who received [177Lu]Lu-DOTA-TATE in Italy are similar to those of the GEP-NET population of NETTER 1 with trial but with a higher proportion of patients with a grade 2 (71%). With regard to the tumor grade profile, our study cohort appears to be closer to that of NETTER-2 study population which included patients with G2 or G3 advanced GEP-NETs (i.e. Ki-67 ≥ 10% and ≤ 55%). Further analysis of effectiveness and safety can be anticipated as REAL-LU data mature. Study Registration: ClinicalTrials.gov, NCT04727723; Study Registration Date: 25 January, 2021; https://clinicaltrials.gov/study/NCT04727723?cond=NCT04727723&rank=1 [ABSTRACT FROM AUTHOR]

Background: Locally infiltrating (T4) differentiated thyroid carcinomas (DTC) represent a challenge. Surgical strategy and adjuvant therapy should be planned balancing morbidity and oncologic outcome. A series of patients with T4 DTC who underwent multidisciplinary evaluation and treatment is reported. The main study endpoints were the oncologic outcome, complication rates, and risk factors for tumor recurrence. Patients and Methods: All DTC cases operated between 2009 and 2021 were reviewed and T4 DTC cases were identified. En bloc resection of inferior laryngeal nerve (ILN), tracheal, and/or internal jugular vein (IJV) was performed in cases of massive infiltration. In cases of pharyngoesophageal junction (PEJ) invasion, the shaving technique was always applied. Results: Among 4775 DTC cases, 60 were T4. ILN infiltration was documented in 45 cases (en bloc resection in 9), tracheal infiltration in 14 (tracheal resection in 2), PEJ invasion in 11 (R0 resection in 7 cases and < 1 cm residual tissue in 4 cases), IJV resection in 6, and laryngeal in 2. In total, 11 postoperative ILN palsy, 23 transient hypoparathyroidisms, and 2 hematomas requiring reoperation were registered. Final histology showed 7 pN0, 22 pN1a, and 31 pN1b tumors. Aggressive variants were observed in 47 patients. All but 1 patient underwent radioiodine treatment, 12 underwent adjuvant external beam radiation therapy (EBRT), and 2 underwent chemotherapy. At a median follow-up of 58 months, no tumor-related death was registered, and seven patients required reoperation for recurrence. Tracheal invasion was the only significant factor negatively impacting recurrence (p = 0.045). Conclusions: A multidisciplinary approach is essential for the management of T4 DTC. Individualized and balanced surgical strategy and adjuvant treatments, in particular EBRT, ensure control of locally advanced disease with acceptable morbidity. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to update the clinical practice applications and technical procedures of sentinel lymph node (SLN) biopsy in vulvar cancer from European experts. Methods: A systematic data search using PubMed/MEDLINE database was performed up to May 29, 2019. Only original studies focused on SLN biopsy in vulvar cancer, published in the English language and with a minimum of nine patients were selected. Results: Among 280 citations, 65 studies fulfilled the inclusion criteria. On the basis of the published evidences and consensus of European experts, this study provides an updated overview on clinical applications and technical procedures of SLN biopsy in vulvar cancer. Conclusions: SLN biopsy is nowadays the standard treatment for well-selected women with clinically negative lymph nodes. Negative SLN is associated with a low groin recurrence rate and a good 5-year disease-specific survival rate. SLN biopsy is the most cost-effective approach than lymphadenectomy in early-stage vulvar cancer. However, future trials should focus on the safe extension of the indication of SLN biopsy in vulvar cancer. Although radiotracers and optical agents are widely used in the clinical routine, there is an increasing interest for hybrid tracers like indocyanine-99mTc-nanocolloid. Finally, it is essential to standardise the acquisition protocol including SPECT/CT images, and due to the low incidence of this type of malignancy to centralise this procedure in experienced centres for personalised approach. [ABSTRACT FROM AUTHOR]

Surgical cure cannot be achieved in most patients with invasive non-functioning pituitary macroadenoma (NFPA). Short-term residual tumor treatment with somatostatin analogs has produced disappointing results. This prospective case-control study assessed the efficacy of chronic treatment with long acting octreotide (octreotide LAR) on tumor volume in patients harboring post-surgical NFPA residue. The study population comprised 39 patients with NFPAs not cured by surgery. All patients underwent somatostatin receptor scintigraphy at least 6 months after the last surgery. Patients with a positive pituitary level octreoscan at (n = 26) received octreotide LAR (20 mg every 28 days) for ≥12 months (mean follow-up 37 ± 18 months) (Treated group). Moreover, a fragment of tumor tissue from patients in the treated group was retrospectively collected to assess the immunohistochemical expression of somatostatin receptor subtypes (SSTRs). The patients with a negative octreoscan (n = 13) formed the control group (mean follow-up 37 ± 16 months). Hormonal, radiological and visual field parameters were periodically assessed. In the treated group, all tumors expressed at least one SSTR subtype. The SSTR5 subtype was the most abundant, followed by SSTR3. The tumor residue increased in five of 26 patients (19%) in the treated group and in seven of 13 controls (53%). Visual field and pituitary function did not change in any patient. This study indicates that SSTR5 and SSTR3 are the most frequently expressed SSTR subtypes in NFPAs and supports a potential role of SSTR subtypes in stabilization of tumor remnant from NFPAs. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively evaluate and compare F-FDG, F-DOPA and Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels. Methods: Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis. Results: At least one focus of abnormal uptake was observed on PET/CT in 13 patients with F-DOPA (72.2% sensitivity), in 6 patients with Ga-somatostatin analogues (33.3%) and in 3 patients with F-FDG (16.7%) ( p < 0.01). There was a statistically significant difference in sensitivity between F-DOPA and F-FDG PET/CT ( p < 0.01) and between F-DOPA and Ga-somatostatin analogue PET/CT ( p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. F-DOPA PET/CT detected 85% of lesions (61 of 72), Ga-somatostatin analogue PET/CT 20% (14 of 72) and F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers ( p < 0.01). In particular, post-hoc tests showed a significant difference in the number of lymph node, liver and bone lesions detected by F-DOPA PET/CT and F-FDG PET/CT ( p < 0.01 for all the analyses) and by F-DOPA PET/CT and Ga-somatostatin analogue PET/CT ( p < 0.01 for all the analyses). The PET/CT results led to a change in management of eight patients (44%). Conclusion: F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than F-FDG and Ga-somatostatin analogue PET/CT. F-FDG may complement F-DOPA in patients with an aggressive tumour. [ABSTRACT FROM AUTHOR]

Ileal pouch-anal anastomosis (IPAA) is now the procedure of choice for most patients requiring proctocolectomy for ulcerative colitis. The J-shaped pouch, usually 15-20 cm in length, is easiest to construct and has functional outcomes identical to those of the more complex designs. IPAA is a complex procedure, and complications occur frequently. Despite the significant improvements this surgical advance has made on the quality of life in these patients, inflammation of the surgically created ileal pouch or pouchitis remains a major late postoperative complication that can often overshadow the benefits of this otherwise curative operation. Several inflammatory and noninflammatory complications can occur after IPAA. Pouchitis is the most common, occurring in ≈50% of patients. Whereas acute pouchitis can be treated rapidly and successfully in the majority of patients, refractory and chronic pouchitis remain therapeutic challenges to patients and physicians. The problem is believed to be caused by stasis of feces in the pouch with overgrowth of aerobic and anaerobic organisms. The size of the pouch has a significant influence on the incidence of pouchitis: a smaller pouch usually empties better than a larger pouch and so may be less susceptible to pouchitis. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Impaired intestinal permeability (IP) may have a role in the pathogenesis of ascites and in spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis (LC). The aim of this study was to assess IP in LC patients with respect to healthy controls.METHODS:IP was evaluated by the 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) permeability test in 52 LC patients and in 48 sex- and age-matched controls. The presence of 51Cr-EDTA was also evaluated in ascitic fluid after therapeutic paracentesis in all LC patients with ascites.RESULTS:An altered IP was found in 45% of LC patients compared with 4% of controls (P<0.00001). IP impairment was significantly associated with Child–Pugh status (75% of Child C patients vs. 39% of Child B and 22% of Child A patients), with the presence of ascites (60% in ascitic patients vs. 31% in nonascitic patients), and with a history of SBP (100% of patients with SBP vs. 50% of those without SBP). 51Cr-EDTA was present in all ascitic samples obtained from patients with SBP compared with 22% of patients without SBP.CONCLUSIONS:IP derangement was a common finding in LC, especially in patients with more advanced disease (presence of ascites and history of SBP). The presence of 51Cr-EDTA in ascites in patients with SBP suggests an altered permeability of splancnic vessels and/or peritoneal membranes. Further studies are required to assess 51Cr-EDTA urine and ascite cutoffs to set up SBP preventive strategies. [ABSTRACT FROM AUTHOR]

Zenker's diverticulum (ZD) is a rare pathology, with a prevalence of between 0.01% and 0.11%. Definitive diagnosis of ZD can be accomplished by contrast radiographic examination (barium oesophagogram, BE); oesophageal manometry (ME) is recommended mainly for those patients suffering from dysphagia and/or gastro­oesophageal reflux. The aims of the present study were to assess whether oropharyngo­oesophageal scintigraphy (OPES) is able (a) to visualise ZD and (2) to demonstrate the corresponding alteration in the swallowing phases. We studied 16 patients (nine male, seven female, mean age 67.4 years), and 17 healthy volunteers (ten male, seven female, mean age 53 years) as a control group. All the patients underwent ME, BE and OPES. Nine patients underwent surgery and six of them were re-evaluated after 6 months. We administered 10 ml of water with 37 MBq of technetium-99m colloid through a straw, acquiring 480 sequential images (0.125 s/frame for a total of 60 s) with the patient standing in front of the gamma camera in the 80° right anterior oblique position. Two static images were performed at the end of the dynamic phase, before and after ingestion of 100 ml of unlabelled water to evaluate the presence of inflammation (persistence of radioactivity in the diverticulum or oesophagus). Study of the sequential scintigraphic images and time-activity curves permitted both qualitative (diverticulum visualisation, multiple deglutitions, reflux, presence of inflammation) and quantitative analyses [oral, pharyngeal and oesophageal transit times and retention indexes, tracheal aspiration percentage] of swallowing disorders. OPES showed a good correlation with the results of other diagnostic techniques usually performed in patients with this pathology, and especially with ME in the evaluation of oropharyngeal phase disorders. Furthermore, OPES is a sensitive and simple technique that is well tolerated and entails a low irradiation dose for patients. [ABSTRACT FROM AUTHOR]

Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin tumor. Currently, 18F-fluoro-deoxy-glucose (18F-FDG) PET/CT is the functional imaging modality of choice. Few data are available on the use of 68Ga-somatostatin analogs. The aim of our study was to evaluate and compare the diagnostic performance of 18F-FDG and 68Ga-somatostatin analog PET/CT in MCC patients.Results: Fifteen patients (12 males, 3 females; median age 73 years; range 41-81 years) with histologically proven MCC (4 with unknown primary lesion) who underwent both 18F-FDG and 68Ga-somatostatin analog PET/CT for staging, re-staging, or treatment response assessment were retrospectively evaluated. Results of both studies were qualitatively analyzed and compared on a patient- and lesion-based analysis, using histology or clinical/radiological follow-up as reference standard for final diagnosis. According to final diagnosis, 8/15 patients had at least one MCC lesion and 7/15 had no evidence of disease. On a patient-based analysis, 18F-FDG and 68Ga-somatostatin analogs correctly classified as positive 8/8 (100% sensitivity) patients and as negative 6/7 (85.7% specificity) and 5/7 (71.4% specificity) patients, respectively, with no significant difference. On a lesion-based analysis, 18F-FDG detected 67/75 lesions (89%) and 68Ga-somatostatin analogs 69/75 (92%), with no significant difference. In four patients with unknown primary MCC, both tracers failed to identify the primary MCC site.Conclusions: Our preliminary data suggest that 18F-FDG and 68Ga-somatostatin analog PET/CT provide good and equivalent diagnostic performance, adding interesting insights into the complex MCC biology. However, these results do not suggest that 18F-FDG PET/CT should be replaced by 68Ga-somatostatin receptor imaging, which should be performed in addition, according to clinical indication, to the perspective of “personalized medicine.” [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article in previous issue about the use of dosimetry to assess for the ablation of thyroid remnants by Flux and colleagues.