Predictive factors of selective transarterial embolization failure in acute renal bleeding: a single-center experience.

PURPOSE: Transarterial embolization of renal artery branches (RTE) is a minimally invasive procedure commonly performed in life-threatening renal bleeding of different etiologies. Despite the widespread use of RTE, no consensus guidelines are currently available. Our aim was to investigate clinical and technical efficacy and to identify potential predictors for clinical failure of this procedure. METHODS: All the RTE procedures performed in our Interventional Radiology unit in last 10 years were retrospectively collected and analyzed. All selected patients underwent both pre-procedural computed tomography angiography (CTA) and post-procedural CTA within 30 days. Clinical success was considered as primary endpoint. Demographic, laboratory, and diagnostic findings predictive of clinical failure of RTE were identified. RESULTS: Over a total of 51 patients enrolled, 27 (53%) were females and 33 (64.7%) had a renal bleeding of iatrogenic origin. Technical and clinical success was 100% and 80.4%, respectively. Hematoma volumes > 258.5 cm3 measured at CTA, higher pre- and post-procedural serum creatinine (Scr) levels, an increase in Scr value > 0.135 mg/dl after the procedure, a worse post-procedural estimated glomerular filtration rate (eGFR), a post-procedural reduction of eGFR < 3.350 ml/min, and a post-procedural reduction of platelet count (PLT) > 46.50 × 103/mmc showed a significantly higher rate of clinical failure. CONCLUSION: RTE is a safe and effective procedure in the management of acute renal bleeding of various origins. Hematoma volume, Scr, PLT, and eGFR values were found to be predictive factors of poor clinical outcome and should be closely monitored.

Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy. Primary analysis of the GARIBALDI survey.

BACKGROUND: Information about the adherence to scientific societies guidelines in the 'real-world' therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). PATIENTS AND METHODS: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. RESULTS: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine + capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel + gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nab-paclitaxel + gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). CONCLUSIONS: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

Safety and preliminary activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody gatipotuzumab with the anti-EGFR tomuzotuximab in patients with refractory solid tumors.

BACKGROUND: The phase I GATTO study (NCT03360734) explored the feasibility, tolerability and preliminary activity of combining gatipotuzumab, a novel humanized monoclonal antibody binding to the tumor-associated epitope of mucin 1 (TA-MUC1) and an anti-epidermal growth factor receptor (anti-EGFR) antibody in refractory solid tumors. PATIENTS AND METHODS: Initially the study enrolled primary phase (PP) patients with EGFR-positive metastatic solid tumors, for whom no standard treatment was available. Patients received gatipotuzumab administered at 1400 mg every 2 weeks, 6 weeks after the start of the glyco-optimized anti-EGFR antibody tomuzotuximab at 1200 mg every 2 weeks. As this regimen was proven safe, enrollment continued in an expansion phase (EP) of patients with refractory metastatic colorectal cancer, non-small-cell lung cancer, head and neck cancer and breast cancer. Tomuzotuximab and gatipotuzumab were given at the same doses and gatipotuzumab treatment started 1 week after the first dose of the anti-EGFR antibody. Additionally, investigators could use a commercial anti-EGFR antibody in place of tomuzotuximab. RESULTS: A total of 52 patients were enrolled, 20 in the PP and 32 in the EP. The combined treatment was well tolerated and no dose-limiting toxicity was observed in the whole study, nor related serious adverse event or death. Preliminary activity of the combination was observed, with one and four RECIST partial responses in the PP and EP, all in colorectal cancer patients. The trial was accompanied by a comprehensive translational research program for identification of biomarkers, including soluble TA-MUC1 (sTA-MUC1) in serum. In the EP, patients with baseline sTA-MUC1 levels above the median appeared to have improved progression-free survival and overall survival. CONCLUSIONS: Combination of a TA-MUC1-targeting antibody and an EGFR-targeting antibody is safe and feasible. Interesting antitumor activity was observed in heavily pretreated patients. Future studies should test this combination together with chemotherapy and explore the potential of sTA-MUC1 as a companion biomarker for further development of the combination.

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey.

BACKGROUND: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting. PATIENTS AND METHODS: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed. RESULTS: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS. CONCLUSIONS: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.

Germinal BRCA1-2 pathogenic variants (gBRCA1-2pv) and pancreatic cancer: epidemiology of an Italian patient cohort.

OBJECTIVE: Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. MATERIALS AND METHODS: Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient's family history was considered as potentially BRCA-associated. Patients or disease characteristics were examined using the χ2 test or Fisher's exact test for qualitative variables and the Student's t-test or Mann-Whitney test for continuous variables, as appropriate. RESULTS: Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P = 0.01). The gBRCApv rate was 17.1% among patients <40 years old, 10.4% among patients 41-50 years old, 9.2% among patients 51-60 years old, 6.7% among patients aged 61-70 years, and 6.2% among patients >70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients <74 years old was 9%. Patients with/without a family history of potentially BRCA-associated tumors had 14%/6% mutations. CONCLUSION: Based on our findings of a gBRCApv incidence higher than expected in a real-life series of Italian patients with incident PDAC, we recommend screening all PDAC patients <74 years old, regardless of family history and stage, due to the therapeutic implications and cancer risk prevention in patients' relatives.

Percutaneous transluminal angioplasty alone versus stent placement for the treatment of transplant renal artery stenosis.

PURPOSE: The purposes of this retrospective study were to assess the efficacy of endovascular techniques for the treatment of transplant renal artery stenosis (TRAS) by analyzing technical and clinical success and to compare the results of percutaneous transluminal angioplasty (PTA) alone to those of stenting. MATERIALS AND METHODS: A retrospective analysis was conducted on 31 patients who underwent endovascular treatment for TRAS between January 2012 and December 2017. There were 23 men and 8 women with a mean age of 60.5±14 (SD) years (range: 24-81 years). Ten patients (10/31; 32%; 8 men, 2 women; median age, 63 years) were treated with PTA alone and 21/31 (68%; 15 men, 6 women; median age, 65 years) with metallic stent placement. Several variables including serum creatinine level, glomerular filtration rate, arterial blood pressure value, antihypertensive medication obtained before and after treatment were compared. Technical success was assessed for each procedure. Clinical success was defined as a 15% drop in serum creatinine level, a decrease greater than 15% in mean blood pressure values or a decrease greater than 10% in mean blood pressure values with a reduction in the number of antihypertensive drugs needed for hypertension control. RESULTS: Technical success was obtained in all patients [31/31; 100%; 95% confidence interval (CI): 89-100%] and clinical success in 27/31 patients (87%; 95%CI: 71-95%). Four patients (4/31; 13%; 95%CI: 5-29%) underwent repeat endovascular intervention. Mean serum creatinine level and mean arterial blood pressure values were significantly lower after treatment (177.4 and 93.8µmol/l, respectively) compared to before treatment (319.4 and 106.7µmol/l, respectively) in the stent group but not in the group treated with PTA alone (P=0.0012 and P=0.002, respectively). CONCLUSION: The endovascular approach is safe and effective in the management of TRAS and stenting, depending on the morphology of the stenosis, should be the treatment of choice when possible.

[Stereotaxic breast microhistology]. / Microistologia mammaria nella stereotassi.

Mammography is currently the most reliable imaging technique to detect clinically occult breast cancer. Stereotaxic-guided aspiration biopsy during mammography allows lesion nature to be diagnosed in many cases. Our experience with 72 microhistologic breast samplings with fine-needle aspiration cytology is reported; 50% of inadequate cytologic samplings were avoided. Adequate cytologic samples were obtained in 88.9% of cases, while microhistologic samples were adequate in 94.4% of cases. Inadequate samples were 11.1% and 5.6%, respectively. Microhistologic biopsies yielded fewer questionable results than fine-needle aspiration cytology, which helped reduce the number of unnecessary biopsies. This method, which is reliable and well tolerated by the patients, can be considered as a valuable alternative procedure to fine-needle aspiration cytology.

[The factor of magnification in mammography]. / Considerazioni sul fattore di ingrandimento in mammografia.

The last generation of mammographic equipment allows mammography to be performed with direct magnification techniques, thanks to such technical features as microfocus, high focus-film distance, high-power generators. The authors compared the diagnostic yield of two different equipment sets, with 1.4x and 2x magnification respectively, and verified the utility of magnification radiography. A significant reduction was obtained in questionable diagnoses (42 to 18) in a group of 63 patients, with no evidence of substantial differences in the diagnostic yield of the images obtained with different magnification ratios. An objective analysis of the system resolution power privileges 2x magnification ratio, which however implies an increase in the average dose to the breast. The use of faster recording systems reduces the dose by 50%, though maintaining good image quality.

[The pulsed Doppler echo of the internal mammary artery]. / L'eco-Doppler pulsato dell'arteria mammaria interna.

In this study the authors discuss the results obtained using pulsed Doppler to evaluate internal mammary artery blood flow velocity in normal, dysplastic and neoplastic breasts. The following parameters were evaluated: percentage of artery localization, vessel diameter, and blood flow velocity. One hundred and seventy-five patients were examined by pulsed Doppler US and mammography in the same sitting. US evaluation of the internal mammary artery was possible in 156 cases. These patients were divided into 3 groups according to Wolfe's classification: normal (38 patients), dysplastic (74 patients) and neoplastic (44 patients). The mean blood flow velocity was estimated in each group; a significant difference was observed between normal (11.8 +/- 6 cm/s) and dysplastic (22.5 +/- 11 cm/s) patients. As for neoplastic patients, similar values were observed in benign (20.6 +/- 9 cm/s) and malignant (25.8 +/- 11 cm/s) lesions. Benign and malignant lesions were distinguished also according to Wolfe's parameters. In the patients with malignant lesions and normal breasts there was an increase in blood flow velocity--which was not observed in dysplastic breasts. In benign lesions in normal or dysplastic breasts, the blood flow velocity was similar to that observed in the respective group of nonpathologic breasts.

[Sonographic structural and morphological features of the parathyroid glands in patients on dialysis. Observations concerning 75 patients]. / Aspetti ecostrutturali e morfologici delle paratiroidi in pazienti dializzati. Osservazioni su 75 pazienti.

The results of US study concerning parathyroid glands performed in 75 uremic patients on regular haemodialysis, examined by echography, are reported. The purpose of this research is the identification of the glands and the analysis of their sonographic features. The results show that parathyroids mostly have round shape and regular outlines, usually hypoechoic structure. The authors stress the use of US as a useful tool for visualization and anatomical definition of parathyroids, providing important information for surgical planning.

[Clinical, radiological and ultrasonic correlations in secondary hyperparathyroidism. Observations concerning 75 patients on dialysis]. / Correlazioni cliniche e radio-ecotomografiche nell'iperparatiroidismo secondario. Osservazioni su 75 pazienti dializzati.

The results of a US study on parathyroid glands, performed in 75 hemodialysed patients are reported. The correlation between morphological features of the glands, biochemical and radiological pattern of secondary hyperparathyroidism is stressed. The results show a significant link between gland volume and hematic level of PTH: less interesting appears the correlation with radiological pattern of uremic osteodystrophy.

Effects fo streptozotocin in the WDHA syndrome not amenable to radical surgery.

Two cases of Verner-MOrrison syndrome due to pancreatic carcinoma were treated H. h streptozotocin (STZ) according to the schedule suggested by the Division of Cancer Treatment of the National Cancer Institute. In both patients the drug caused a remission of the WDHA syndrome: therefore, this finding seems to recommend such treatment when the syndrome is not amenable to radical surgery. Renal toxicity is, however, an important limitation. It occurs mostly when STZ is administered by iv infusion. In one of the patients, after a serious impairment of renal function caused by STZ, prednisone controlled the syndrome for a long period of time.

Effects of streptozotocin in the WDHA syndrome not amenable to radical surgery.

Two cases of Verner-Morrison syndrome due to pancreatic carcinoma were treated H. h streptozotocin (STZ) according to the schedule suggested by the Division of Cancer Treatment of the National Cancer Institute. In both patients the drug caused a remission of the WDHA syndrome: therefore, this finding seems to recommend such treatment when the syndrome is not amenable to radical surgery. Renal toxicity is, however, an important limitation. It occurs mostly when STZ is administered by iv infusion. In one of the patients, after a serious impairment of renal function caused by STZ, prednisone controlled the syndrome for a long period of time.

[Multi-institution, multidisciplinary radiology and endoscopy trial of the diagnostic accuracy of the double contrast examination of the stomach surface]. / Trial policentrico multidisciplinare radiologia-endoscopia sul rendimento diagnostico dell'esame a doppio contrasto di superficie dello stomaco.

In 12 X-ray and gastroenterology departments 1570 patients, clinically suspected to have a gastric pathology, have been examined by double contrast (surface) examination of the stomach followed by gastroscopy. Diagnostic accuracy was 93% in respect of endoscopic data, assumed correct by hypothesis. On the basis of a cost and benefit evaluation, made according to the well known criteria, a wider routine use of the double contrast technique is proposed.