Gastroenteropancreatic grade 3 neuroendocrine tumors: a single entity or a heterogeneous group? A retrospective analysis.

PURPOSE: Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed. PATIENTS AND METHODS: We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes. RESULTS: Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3). Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative 68Gallium(68Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (18FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048). CONCLUSION: Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.

Contralateral Axillary Lymph Node Metastases from Breast Carcinoma: Is it Time to Review TNM Cancer Staging?

BACKGROUND: Contralateral axillary lymph node metastasis (CAM) is an infrequent clinical condition currently considered an M1, stage IV, disease. Due to the absence of shared data on CAM significance and on its therapeutic approach, be it curative or simply palliative, its management is still uncertain and undoubtedly represents a clinical challenge. PATIENTS AND METHODS: Patients with pathologically confirmed metachronous CAM were retrospectively evaluated. All patients had been managed at the European Institute of Oncology, Milan, Italy, from 1997. Patients with distant metastases at the time of CAM were excluded. Possible treatments included surgery, systemic therapy and RT (radiotherapy). Outcomes were evaluated as rates of disease-free survival (DFS) and of overall survival (OS). RESULTS: Forty-seven patients with CAM were included in the study. Metachronous CAM occurred 73 months (range 5-500 months) after diagnosis of the primary tumor. The median follow-up time was 5.4 years (interquartile range 2.9-7.0 years). The estimated OS was 72% at 5 years (95% CI 54-83), and 61% at 8 years (95% CI 43-75). The estimated DFS was 61% at 5 years (95% CI 44-74), and 42% at 8 years (95% CI 25-59). CONCLUSION: These findings, together with those from previous studies, show that CAM outcome, particularly if measured as OS, appear better than at other sites of distant dissemination, when CAM is subjected to surgical and systemic treatments with a curative intent. Therefore, a new clinical scenario is suggested where, in the TNM system, CAM is no longer classified as a stage IV, but as an N3 disease.

Predicting the Need for Intra-operative Large Volume Blood Transfusions During Thoraco-abdominal Aortic Aneurysm Repair.

OBJECTIVE: Thoraco-abdominal aortic aneurysm (TAAA) repair is a complex procedure performed in patients at high cardiovascular risk. High volume intra-operative bleeding is often recorded, and the amount of intra-operative blood product transfusion is associated with relevant morbidity and mortality. The aim of the study was to identify pre-operative predictors of intra-operative large volume blood transfusions (LVBT) to stratify patients pre-operatively. METHODS: This was a retrospective analysis of prospectively collected data of all patients who underwent open TAAA surgery at San Raffaele Scientific Institute from January 2009 to December 2015. Intra-operative red blood cell (RBC) transfusions were administered to maintain a hematocrit of at least 30%. A LVBT was defined as a transfusion of at least four RBC units, corresponding to 1000 mL. RESULTS: The study population included 428 patients: 260 (61%) received fewer than 4 RBC units, and 168 (39%) were transfused with at least 4 RBC units. In patients who underwent LVBT, higher mortality was observed after surgery (p=.003), longer intensive care unit admission (p=.004), and longer mechanical ventilation compared with less transfused patients (p=.0002). The patients who received fewer units were administered a higher dose of heparin during the surgical operation compared with patients of the LVBT group: 3400±1100 vs. 2900±1300 IU (international units) (p=.0004). Pre-operative chronic renal failure (OR 1.8), the pre-operative haemoglobin value (OR 0.8), and the need for urgent or emergent surgery (OR 3.15) were independent predictors of LVBT on multivariate analysis. CONCLUSIONS: The identification of patients at risk of intra-operative LVBT during TAAA surgery is critical as these patients experience a worse outcome. Nevertheless, only few independent predictors are available for clinical practice.

Major hepatectomy for perihilar cholangiocarcinoma in elderly patients: is it reasonable?

INTRODUCTION: We sought to evaluate the effect of age on postoperative outcomes among patients undergoing major liver surgery for perihilar cholangiocarcinoma (PHCC). METHODS: 77 patients were included. Patients were categorized into two groups: the "< 70-year-olds" group (n = 54) and the "≥ 70-year-olds" group (n = 23). RESULTS: Median LOS was 19 both for < 70-year-old group and ≥ 70-year-old group (P = 0.72). No differences in terms of severe complication were detected (44.4% Clavien-Dindo 3-4-5 in < 70-year-old group vs 47.8% in ≥ 70-year-old group, P = 0.60). Within 90 postoperative days, 11 patients died, 6 in < 70-year-old group (11.3%) and 5 in ≥ 70-year-old group (21.7%), P = 0.29. The median follow-up was 20 months. The death rate was 72.2% and 78.3% among patients < 70 years old and ≥ 70 years old. The OS at 2 and 5 years was significantly higher among the < 70 years old (57.0% and 27.7%) compared to the ≥ 70 years old (27.1% and 13.6%), P = 0.043. Adjusting for hypertension and Charlson comorbidity index in a multivariate analysis, the HR for age was 1.93 (95% CI 0.84-4.44), P = 0.12. Relapse occurred in 43 (81.1%) patients in the < 70-year-old group and in 19 (82.6%) patients in the ≥ 70-year-old group. DFS at 12, 24, and 36 months was, respectively, 59.6, 34.2, and 23.2 for the < 70 -year-old group and 32.5, 20.3, and 13.5 for the ≥ 70-year-old group (P = 0.26). Adjusting for hypertension and Charlson comorbidity index in a Cox model, the HR for age was 1.52 (95% CI 0.67-3.46), with P = 0.32. CONCLUSIONS: ≥ 70-year-old patients with PHCC can still be eligible for major liver resection with acceptable complication rates and should not be precluded a priori from a radical treatment.

[Object permanence in children with neurological and psychomotor disorders]. / La permanenza dell'oggetto nei bambini con disturbi neuro- e psicomotori. Un indicatore affidabile dello sviluppo psicomotorio.

The aim of this research was to investigate whether the development of object permanence is an available sign of the cognitive development in infants with psychomotor handicaps. Subjects consisted of 5 males, ranging in age from 12 to 33 months, with handicaps as a result of perinatal brain injury. Four were preterm infants. All of the children received psychomotor treatment. Their stage of object permanence was assessed using traditional (B-L) and non traditional test (U-H). (The children's performances on the U-H scales have an "Intrinsic validity"). Four children achieved the first stages of the development of object permanence. The acquisition of object permanence was delayed in comparison with the age-appropriated time, but it may be considered adequate in comparison with the "developmental age" (B-L). One children with severe mental and motor disorders solved no task, the findings suggest that the children with psychomotor handicaps may gain the concept of object permanence and that psychomotor treatment may assist them in the development of the concept. This performance is not age-dependent. So the acquisition of the concept of object permanence may be considered an accurate and sensitive tool for the follow-up of the sensorimotor development in the handicapped children.