The challenge of the differential diagnosis between brown tumors and metastases in parathyroid carcinoma: a case report.

Background: Brown tumors are rare bone manifestations of primary hyperparathyroidism (PHPT) that may occur at different sites either as single or multiple lesions and they can easily be mistaken for malignant lesions. Neither bone site nor morphological or functional imaging are useful to drive the differential diagnosis and biopsy is often the only conclusive procedure. Case description: We report the case of a 53 years-old man referred to our outpatient clinic for severe symptomatic PHPT complicated by nephrolithiasis and osteoporosis. Neck ultrasound and computed tomography (CT) scan showed a large irregular lesion posterior to the lower pole of the right thyroid lobe consistent with an enlarged parathyroid gland. Moreover, two bone lytic lesions were described at the left scapula and the contiguous 7th rib that showed an increased uptake at total bone scintigraphy. Given the clinical and biochemical picture, the features of the parathyroid lesion and the presence of bone lytic lesions, the suspicion of metastatic parathyroid carcinoma (PC) was raised. However, a CT-guided biopsy performed on the left scapula revealed a brown tumor. The patient underwent en-bloc resection of the right inferior parathyroid grand with the ipsilateral thyroid gland lobe. Histopathology confirmed the diagnosis of PC. Post-surgical biochemical evaluations showed that the patient was cured. A repeated total body CT scan revealed an osteoblastic appearance of the bone lesions ascribed to the partial regression of the brown tumors following surgery. Conclusions: The implication of a diagnosis of brown tumor or bone metastasis is widely different; in fact, the first tends to regress with the surgical treatment of PHPT, whereas the latter has limited cure option and negatively affects the prognosis of patients. Therefore, although brown tumors are extremely rarer than in the past, they must always be taken into consideration in the presence of bone lesions, even in cases of high suspicion of malignancy, to avoid unnecessary and harmful surgical interventions.

Significance of Thyroglobulin Autoantibodies in Patients With Thyroid Cancer Treated With Lenvatinib.

Context: Serum thyroglobulin (Tg) is a highly sensitive and specific tumor marker, employed in post-operative management of patients with differentiated thyroid carcinomas. Tumor shrinkage of radioiodine-refractory thyroid cancer (RAIR-DTC) treated with multitarget kinase inhibitors as lenvatinib, expressed according to the Response Evaluation Criteria in Solid Tumors (RECIST), is also associated with a drastic reduction of Tg levels. However, interference caused by circulating thyroglobulin autoantibodies (TgAb) represents the main limitation in the clinical use of Tg. Objective: To evaluate if in RAIR-DTC TgAb could be considered a surrogate marker of Tg in monitoring response to treatment with lenvatinib. Design: We retrospectively evaluated patients who had started lenvatinib and correlated serum Tg and TgAb with the radiological response across visits. Setting: University of Pisa, Italy. Patients: We selected 9/97 RAIR-DTC patients with detectable TgAb. Intervention: None. Main Outcome Measures: None. Results: Tg values correlated neither with TgAb title nor with radiological response across visits. Greater decreases in TgAb titer correlated with favorable radiological response to lenvatinib after 1 month (Spearman's correlation = 0.74, P = .021) and 6 months (correlation = 0.61, P = .079). According to RECIST, patients with partial response showed a ∼10-fold greater decrease in TgAb compared to those with stable disease at 1 month (median TgAb decrease: -142 vs -14 IU/mL, P = .01) and those with progressive disease at 6 months (median TgAb decrease: -264 vs-24 IU/mL, P = .04). Conclusion: TgAb evaluation may represent a reliable surrogate marker for Tg trend in evaluating response of RAIR-DTC to treatment with lenvatinib. A multicentric study would be useful to confirm our results.

ShorTrip Trial: A Prospective, Multicentric Phase II Single-Arm Trial of Short-Course Radiotherapy Followed by Intensified Consolidation Chemotherapy With the Triplet FOLFOXIRI as Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

BACKGROUND: In patients with locally advanced rectal cancer (LARC) treated with preoperative (chemo) radiotherapy and surgery, adjuvant chemotherapy is poorly feasible and its benefit is questionable. In the last years, several total neoadjuvant treatment (TNT) strategies, moving the adjuvant chemotherapy to the neoadjuvant setting, have been investigated with the aim of improving compliance to systemic chemotherapy, treating micrometastases earlier and then reducing distant recurrence. PATIENTS AND METHODS: ShorTrip (NTC05253846) is a prospective, multicentre, single-arm phase II trial where 63 patients with LARC will be treated with short-course radiotherapy followed by intensified consolidation chemotherapy with FOLFOXIRI regimen and surgery. Primary endpoint is pCR. Among the first 11 patients who started consolidation chemotherapy, a preliminary safety analysis showed a high rate of grade 3 to 4 neutropenia (N = 7, 64%) during the first cycle of FOLFOXIRI. Therefore, the protocol has been emended with the recommendation to omit irinotecan during the first cycle of consolidation chemotherapy. After amendment, in a subsequent safety analysis focused on the first 9 patients treated with FOLFOX as first cycle and then with FOLFOXIRI, grade 3 to 4 neutropenia was reported in only one case during the second cycle. AIM OF THE STUDY: The aim of this study is to assess the safety and activity of a TNT strategy including SCRT, intensified consolidation treatment with FOLFOXIRI and delayed surgery. After protocol amendment, the treatment seems feasible without safety concern. Results are expected at the end of 2024.

Total neoadjuvant treatment and organ preservation strategies in the management of localized rectal cancer: A narrative review and evidence-based algorithm.

The multimodal approach with total mesorectal excision preceded by neoadjuvant (chemo)radiotherapy represented the mainstay treatment for locally advanced rectal cancer (LARC) for a long time. However, the benefit of adjuvant chemotherapy in terms of distant relapse reduction is limited. Recently, chemotherapy regimens administered before surgery and incorporated with (chemo)radiotherapy in total neoadjuvant treatment protocols have been established as new options in the management of LARC. Meanwhile, patients with clinical complete response to neoadjuvant treatment can benefit from organ preservation strategies, aimed at sparing surgery and long-term post-operative morbidities, while preserving an adequate disease control. However, the introduction of a non-operative management in clinical practice is a matter of debate with some concerns regarding the risk of local recurrence and long-term outcomes. In this review, we discuss how these recent advances are reshaping the multimodal management of localized rectal cancer and propose an algorithm to place them in the clinical practice.

The added value of the visual analysis of DWI in post-surgery follow-up of soft tissue sarcoma of the extremities: do we really need ADC?

INTRODUCTION: MRI has a fundamental role in the follow-up of soft tissue sarcomas (STSs). However, the differentiation of recurrences/residual disease from post-surgical changes is a complex task, with a central role for the radiologist. MATERIALS AND METHODS: We retrospectively evaluated 64 post-surgery MRI for extremities STSs. MR protocol included DWI (b = 0, 1000). Two radiologists were asked to consensually evaluate: presence/absence of tumoral nodules, lesion conspicuity, imaging diagnostic confidence, ADC values, and DWI overall image quality. The gold standard was histology or MR follow-up. RESULTS: Thirty-seven lesions in 29/64 patients were confirmed as local recurrence or residual disease (n = 16 ≤ 1 cm) with 1 MR false positive. On DWI, the conspicuity of the proved tumor lesions resulted excellent in 29/37, good in 3/37 and low in 5/37, higher than conventional imaging. A statistically significant higher diagnostic confidence of DWI compared to conventional imaging (p < 0.001) and DCE (p = 0.009) was observed. In the 37 histologically confirmed lesions, mean ADC value was 1.31 × 10-9 m2/s. Overall scar tissues mean ADC was 1.70 × 10-9 m2/s. DWI quality resulted adequate in 81% and unsatisfactory in 5%. CONCLUSIONS: In this highly heterogeneous group of tumors, the role of ADC seems to be limited. Based on our experience, looking at DWI images makes the lesions promptly and easily detectable. This technique gives less deceptive findings making the reader more confident in detecting/excluding tumoral tissue; the main drawback is the image quality and the lack of standardization.

Peyronie's disease development and management in diabetic men.

BACKGROUND: Peyronie's disease (PD) is a fibrosing disorder of the penis resulting in plaque formation and penile deformity that negatively affect sexual and psychosocial function of patients. A multifactorial etiology of PD is assumed with diabetes mellitus (DM) being a potential risk factor. OBJECTIVES: The aim of this narrative review was to investigate diabetes role in PD pathophysiology, diagnosis, and treatment. MATERIALS AND METHODS: A non-systematic narrative review of original articles, meta-analyses, and randomized trials was conducted, including articles in the pre-clinical setting to support relevant findings. RESULTS: Diabetes is one of the most common comorbidity observed in PD patients, with a prevalence of about 11% and a strong association with erectile dysfunction (ED). DM is associated with both a higher risk of developing PD and has also an impact on the outcomes of PD's treatments. DISCUSSION: Evidence from literature underlines that metabolic alterations typical of DM are pivotal factors in the development of PD and resistance to its medical treatment. CONCLUSION: The role of DM in development of PD is still debated, while its role in PD development is not completely clear, there is a clear impact of DM on PD treatment outcomes.

Type 2 diabetes albuminuric and non-albuminuric phenotypes have different morphological and functional ultrasound features of diabetic kidney disease.

AIMS: Whether different diabetic kidney disease (DKD) phenotypes recognise differences in morphological and vascular properties of the kidney is still unexplored. We evaluated the potential role of kidney ultrasonography in differentiating DKD phenotypes in subjects with type 2 diabetes. MATERIALS AND METHODS: This is a cross-sectional, single-centre study. Total (TRV) and parenchymal renal volumes (PRV) were calculated by applying the ellipsoid formula for conventional (2D) ultrasonography and with manual segmentation for 3D ultrasonography, and then adjusted for body surface area (aTRV, aPRV). Renal resistive index (RI) was contextually determined. DKD phenotypes have been defined based on increased urinary albumin-to-creatinine ratio (ACR >30 mg/g) and/or reduced eGFR (<60 ml/min/1.73 m2 ). Recruitment was planned to have groups of the same size. RESULTS: Among 256 subjects, 26.2% had No-DKD, 24.6% increased albuminuria only (Alb+ ), 24.2% non-albuminuric DKD (Alb- DKD), and 25.0% albuminuric DKD (Alb+ DKD). Compared to No-DKD, RI was significantly higher in all DKD phenotypes, being the highest in Alb+ DKD, and with a significant trend of RI > 0.70 to increase across phenotypes. In comparison with No-DKD, both 2D and 3D volumes were increased in Alb+ and significantly reduced in Alb- DKD as well as in Alb+ DKD, with significantly lower volumes in Alb- DKD as compared to Alb+ DKD at the same reduced levels of eGFR. In adjusted regressions, compared to No-DKD, RI was associated with Alb+ ; both RI and aPRV3D were associated with Alb+ DKD; only aPRV3D with Alb- DKD. Compared to No-DKD, Receiver Operating Characteristic curve analyses, designed taking into account conventional risk factors, showed that US parameters did not ameliorate the characterisation of Alb+ and Alb+ DKD, while aPRV3D significantly improved the phenotyping of Alb- DKD. CONCLUSIONS: As a novel information, we reported that, in type 2 diabetes, the emerging normoalbuminuric DKD phenotype showed reduced TRVs and PRVs even when compared, at similarly reduced eGFR levels, with Alb+ DKD opening. In perspective, these findings suggest a possible role of imaging for better discrimination of DKD phenotypes in clinical practice.

Chylous effusions in advanced medullary thyroid cancer patients treated with selpercatinib.

Objective: Selpercatinib is a highly selective RET-inhibitor drug, approved for the treatment of RET-altered lung and thyroid cancers. So far, RET-altered medullary thyroid cancer (MTC) patients treated with selpercatinib showed a remarkable objective response rate and safety profile. However, new treatment emerging adverse events (TEAEs) have been recently reported. The aim of this study was to evaluate the prevalence, features, and clinical management of effusions that are one of these TEAEs. Design: Around 10 of 11 patients with advanced MTC enrolled in the LIBRETTO-201 clinical trial at Endocrinology Unit of the Pisa University Hospital were evaluated for the presence and management of effusions. Methods: We retrospectively evaluated MTC patients treated with selpercatinib. The presence of pleural, pericardial, abdominal, and/or pelvic effusions was evaluated by reviewing the computerized tomography scan performed during the study protocol and up to 24 months of observation. Results: All but one MTC patient experienced previous multikinase inhibitors treatment. Three patients already had effusions before starting selpercatinib treatment. New effusions appeared in eight of ten (80%) patients during the treatment. A chylous nature was documented in patients who underwent fluid aspiration. Whenever a dose reduction was performed, a significant positive effect was observed. Conclusions: Chylous effusions are a new TEAE of selpercatinib treatment. They can appear or worsen at any time during the treatment. For cases with asymptomatic and mild effusions, active surveillance may be appropriate and safe. In symptomatic and/or moderate/severe cases, aspiration of the fluid and a dose reduction can improve this AE, strongly supporting a cause-effect correlation with selpercatinib. Significance statement: Effusions, particularly of chylous nature, represent emergent and quite frequent adverse events in the management of patients affected by advanced MTC on treatment with the highly selective inhibitor selpercatinib. In this study, we evaluated, in a series of MTC patients treated with selpercatinib, the prevalence of pleural, pericardial, abdominal, and/or pelvic effusions. Insights into the diagnosis and treatment of the effusions are provided as well as suggestions for clinical management.

Predicting the coagulation volume induced by microwave ablation of hepatocellular carcinoma: the role of deposited energy, ex-vivo bovine liver charts and central hyperdense area on post-treatment CT.

PURPOSE: To study the correlation between the overall coagulation zone (A) attained in percutaneous microwave ablation (MWA) of hepatocellular carcinomas (HCC) and: (1) the hyperdense zone (C) visible in the central part of zone A on post-treatment unenhanced CT scans; (2) the deposited energy; (3) the coagulation zones observed on ex-vivo bovine liver. MATERIALS AND METHODS: The post-procedural computed tomography (CT) scans of HCCs treated with a single energy deployment through the same 2450 MHz MWA system were retrospectively analyzed, retrieving the dimensions of A and C zones and the deposited energy (E). Ex-vivo bovine liver MWA with the same system were performed and analyzed to determine the same quantities by gross-pathologic examination and CT imaging. RESULTS: A total of 101 HCC treatments were analyzed. The average coagulation volumes increased linearly with deposited energy (1.11 cc/kJ, R2 = 0.90, 4.2 kJ ≤ E ≤ 48 kJ), similarly to ex-vivo findings (1.38 cc/kJ, R2 =0.97, 7.2 kJ ≤ E ≤ 144 kJ). The long axis (L) and short axis (D) of zones A and C held a fairly constant ratio both in-vivo (LC/LA=0.43 ± 0.13; DC/DA=0.42 ± 0.10) and ex-vivo (LC/LA = 0.49 ± 0.07; DC/DA = 0.28 ± 0.06). CONCLUSIONS: The average dimensions of the ablation zone induced by the considered system on HCC increase linearly with the deposited energy and are fairly well predicted by the corresponding ex-vivo dimensions. The ratio between each linear dimension of A and C zones was found to be roughly constant over a large deposited energy span, both ex-vivo and in-vivo.

Microwave Ablation of Very-Early- and Early-Stage HCC: Efficacy Evaluation by Correlation with Histology after Liver Transplantation.

Microwave (MW) ablation is a worldwide-diffused technique for the percutaneous ablation of hepatocellular carcinoma (HCC). Nevertheless, the efficacy of this technique still needs to be confirmed in pathological specimens. The purpose of this study was to evaluate the efficacy of MW ablation by correlation with histology in excised liver samples at the time of liver transplantation (LT). All patients with MW-ablated HCC who subsequently underwent LT between 2012 and 2020 were retrospectively evaluated. In the explanted livers, the treated lesions were evaluated at pathology, and the necrosis was classified as complete or partial. Thirty-six HCCs were ablated in 30 patients (20.9 ± 6.1 mm, a range of 10-30 mm). Ablations were performed with a single insertion of a MW antenna under ultrasound or CT guidance. A complete radiological response was demonstrated in 30/36 nodules (83.3%) in 24/30 patients (80%) at imaging performed one-month after MW ablation. At pathology, of the 36 treated nodules, 28 (77.8%) showed a complete necrosis, and 8 (22.2%) showed a pathological partial necrosis. Good agreement was found between the imaging performed one-month after treatment and the complete pathological response (Cohen's k = 0.65). The imaging accuracy in detecting a complete response to treatment was 88.9%. All lesions with complete necrosis did not show recurrence at follow-up imaging until transplantation. The rad-path correlation in the explanted livers showed that MW ablation achieved a high rate of complete necrosis if a macroscopical complete ablation was obtained.

Humeral greater tuberosity osteolysis as a complication of intraosseous calcification migration: natural history depicted by imaging.

Migration of calcification within the bone leading to greater tuberosity osteolysis is a peculiar complication of the calcifying tendinitis of the rotator cuff. The case of a 38-year-old woman complaining of right shoulder pain, which had been going on for one year, is hereby described. The evolution of the infraspinatus tendon calcifying tendinitis leading to osteolysis of the greater tuberosity of the humerus is depicted by imaging and, particularly, by the MR and CT features changing over time. In this paper we focus on the importance of both MR and CT exams in the diagnostic process of the different phases of the disease. The correlation between clinical symptoms and imaging features is also helpful for imaging interpretation: the most painful phase corresponds to the migration of the calcification, whereas pain tends to decrease when the osteolysis develops. Awareness of the existence of this condition may prevent unnecessary invasive procedures.

Increased Use of Blood Transfusions to Manage Urological Conditions during the COVID-19 Pandemic.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to an extensive reorganization of the healthcare system in Italy, with significant deferment of the treatment of urology patients. We aimed to assess the impact of deferred treatment during the SARS-CoV-2 pandemic on the need for blood transfusions in 3 Italian urology departments. METHODS: We reviewed hospital chart data on blood transfusions at the urology units of 3 academic centers in the north of Italy from March to April 2020. Data were compared with values from the same time frame in 2019 (March to April 2019). RESULTS: We observed significant reductions of the number of patients admitted to the urology units from March to April 2020 (373 vs. 119) and the number of performed surgeries (242 vs. 938) compared to 2019. Though, the number of transfused blood units was comparable between the 2 years (182 vs. 252), we found a greater mean number of blood units transfused per admission in 2020 (0.49 vs. 0.22; p < 0.0001). As a whole, the transfusion rate for hematuria was higher in 2020 than in 2019 (36 vs. 7.9%; p < 0.0001). DISCUSSION/CONCLUSION: The observed increased number of blood transfusions needed throughout the SARS-CoV-2 era could have had a negative impact on both patients and the healthcare system. It is possible to speculate that this is the consequence of a delayed diagnosis and deferred treatment of acute conditions.

The impact of training on diagnostic accuracy with computed tomography coronary angiography.

AIM: The aim of this study is to assess the image quality and diagnostic accuracy of computed tomography (CT) coronary angiography (CTCA) in different hospital settings with the same trained team. MATERIALS AND METHODS: Four hundred patients were consecutively enrolled for CTCA in a large academic hospital (Group 1; Sensation 64 Cardiac, Siemens - Iomeprol 400, Bracco; 200 patients) and in a small local hospital (Group 2; VCT, GE Healthcare - Iodixanol 320, GE Healthcare; 200 patients). All patients were enrolled for suspected coronary artery disease (CAD) and patients with stents or who had previously undergone coronary bypass were excluded. Scan protocols (retrospectively ECG-gated; no dose reduction modulation applied) were performed in accordance with standards reported in the international literature with the best solution available on site. Image quality was assessed in each coronary segment with a 4-point Likert scale: 0, not assessable; 1, low; 2, average; 3, good. Diagnostic accuracy was calculated against conventional coronary angiography with a threshold of at least 50% for significant stenosis. RESULTS: There was no significant difference between demographics, BMI, prevalence of obstructive CAD, calcium score and heart rate between the two populations. The average image quality was 2.83 ± 0.37 for Group 1 and 2.86 ± 0.31 for Group 2 (P > 0.05). Per-segment sensitivity, specificity, positive and negative predictive values were 92.6% (87-95), 97.9% (97-98), 75.9% (69-81) and 99.5% (99-99), respectively, for Group 1, and 90.4% (85-93), 98.6% (98-99), 84.2% (78-88) and 99.2% (98-99), respectively, for Group 2 (P > 0.05). CONCLUSION: There is no significant difference in image quality and diagnostic accuracy of CTCA when the investigation is performed by the same properly trained team. CTCA is a robust imaging modality for the detection of coronary artery stenosis.