The role of prophylactic central compartment lymph node dissection in elderly patients with differentiated thyroid cancer: a multicentric study.

BACKGROUND: Prophylactic central neck lymph-nodes dissection is still a topic of major debate in Literature. There is a lack of randomized controlled trials proving advantages in its application in terms of overall survival and local recurrence. Due to the recent rapid increase of elderly population, differentiated tumor carcinoma diagnosis increased in patients over 65 years old. The aim of this study was to compare recurrence rate, complications rate and histological features of tumors in elderly population. METHODS: A retrospective study was carried out collecting data from 371 patients with differentiated thyroid cancer without clinical evidence of lymph-nodes involvement in three Italian referral centers from 2005 to 2015. All patients were aged ≥ 65 years and were divided in two groups based on the performed surgery (total thyroidectomy alone or associated with central lymph-nodes dissection). Moreover, patients were stratified according to the age between 65 and 74 years old and over 75 years old. RESULTS: Total thyroidectomy alone was performed in 184 patients (group A) and total thyroidectomy with prophylactic central neck dissection was performed in 187 cases (group B). There was a statistically significant difference in complications between the groups in terms of neck hematoma (0.5% group A vs 3.7% group B), temporary hypoparathyroidism (11.4% group A vs 21.4% group B), and temporary unilateral recurrent nerve injury (1.5% group A vs 6.4% group B). Lymph nodes recurrence rate was 9.2% in group A and 8.5% in group B, with no statistically significant difference. There was a statistically significant difference in patients over 75 years old in terms of temporary hypoparathyroidism (24% group A vs 11% group B), permanent hypoparathyroidism (2,7% group A vs 0,3% group B) and recurrent nerve injury (9,5% group A vs 2% group B). CONCLUSIONS: The role of prophylactic central neck dissection is still controversial, especially in elderly patients, and an aggressive surgical approach should be carefully evaluated. The Authors reported a similar low recurrence rate between total thyroidectomy and total thyroidectomy associated with prophylactic central neck dissection, with increased postoperative complications in the lymphadenectomy group and in patients over 75 years old, advocating a tailored surgical approach in elderly population.

The impact of the ultrasonic, bipolar and integrated energy devices in the adrenal gland surgery: literature review and our experience.

BACKGROUND: The gold standard approach for surgical treatment of benign and malignant adrenal lesion is considered the laparoscopic one, due to a lot of advantages compared to open approach. The rapid propagation of this surgical technique is due to the diffusion of haemostatic devices in laparoscopic adrenal surgery. The principal aim of this study is to analyze the outcome of LA using each energy modality, evaluating the eventual superiority of an instrument over the others. METHODS: A retrospective study, involving 75 consecutive patients submitted to LA by transperitoneal lateral approach from January 2013 to June 2017, was performed. Age less than 70 years old, adrenal adenomas less than 8 cm in diameter, incidentalomas < 6 cm, myelolipomas < 13 cm, adrenal metastases < 7 cm and ASA score ≤ III were the main surgical inclusion criteria. All involved patients were divided into three group, one for each energy device: group 1 - Harmonic Scalpel, group 2 - Ligasure vessel sealing system and group 3 - Thunderbeat. In each group only one device was applied for dissection and haemostasis during the whole operation. Each group consisted of 25 patients, well matched for histology, tumor size and site, gender and age. The following parameters were collected: age, gender, size of the tumor, side of the affected gland, pathology, operating time, intraoperative blood losses, hospitalization time, complication and conversion rate. RESULTS: There was no significant statistical difference between groups regarding the relationship between male/female, right site/left site, the mean age, hospitalization time and the tumor size (p > 0.05). Significant statistical difference are detectable in operation time and intraoperative blood losses. Thunderbeat, compared respectively with Ligasure and Harmonic Scalpel, is the fastest device (p < 0,001). The second faster device resulted Harmonic Scalpel, which meanly reduced the operation time compared to Ligasure (p = 0.048). intraoperative blood losses are reduced using Thunderbeat (p < 0,001) and HS (p = 0.006) compared to Ligasure, but between Thunderbeat and Harmonic Scalpel there isn't significant statistical difference (p = 0.178). CONCLUSIONS: Analyzing the results, laparoscopic adrenalectomy carried out using Thunderbeat appeared to show a statistically significant decrease in operation time and intraoperative blood losses compared with laparoscopic adrenalectomy performed using Harmonic Scalpel and Ligasure, while hospitalization time was superimposable in all groups. According to our data, a responsible use of advanced energy devices can improve surgical outcomes guarantying a cost savings and patient's satisfaction.

GPI-defective monocytes from paroxysmal nocturnal hemoglobinuria patients show impaired in vitro dendritic cell differentiation.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, acquired hematopoietic disorder characterized by a phosphatidylinositol (PI) glycan-A gene mutation, which impairs the synthesis of the glycosyl-PI (GPI) anchor, thus causing the absence of all GPI-linked proteins on the membrane of the clonal-defective cells. The presence of a consistent GPI-defective monocyte compartment is a common feature in PNH patients. To investigate the functional behavior of this population, we analyzed its in vitro differentiation ability toward functional dendritic cells (DCs). Our data indicate that GPI-defective monocytes from PNH patients are unable to undergo full DC differentiation in vitro after granulocyte macrophage-colony stimulating factor and recombinant interleukin (IL)-4 treatment. In this context, the GPI-defective DC population shows mannose receptor expression, high levels of the CD86 molecule, and impaired CD1a up-regulation. The analysis of lipopolysaccharide and CD40-dependent, functional pathways in these DCs revealed a strong decrease in tumor necrosis factor alpha and IL-12 production. Finally, GPI-defective DCs showed a severe impairment in delivering accessory signals for T cell receptor-dependent T cell proliferation.

Intestinal toxicity during induction chemotherapy with cytarabine-based regimens in adult acute myeloid leukemia.

BACKGROUND: Cytotoxic regimens used in induction treatments for acute myeloid leukemia (AML) almost always include standard or high-dose cytarabine (Ara-C). During or soon after induction therapy, leukemic patients frequently develop gastroenteric complications, characterized by abdominal pain and diarrhea. The association of these symptoms with fever and melena is typical of necrotizing enterocolitis (NE), a life-threatening condition that can be documented by ultrasound abdominal scan. PATIENTS AND METHODS: We analyzed retrospectively the clinical course of 169 adult patients with AML treated by standard dose Ara-C-containing induction regimens, either by continuous venous infusion (group 1) or subcutaneous injection (group 2). Ultrasonography was employed as early diagnostic tool in a majority of patients with gastroenteric complications. Bowel wall thickening was accurately measured and used to confirm the diagnosis of necrotizing enterocolitis. RESULTS: In the first group of 115 patients (median age, 51 years), gastroenteric complications were observed in 55 patients (48%), and 10 patients (9%) received diagnosis of NE, which was fatal in four. Patients with NE had a median age older than that of patients without gastroenteric symptoms, and a more prolonged neutropenia. In the second group of 54 patients (median age, 60 years), gastroenteric events were observed in 14 patients (26%), and no case of NE was recorded. CONCLUSIONS: This retrospective analysis shows that NE is a serious complication occurring mainly in patients treated by Ara-C administered as continuous i.v. infusion.

Tc99m-sestaMIBI uptake in nonsecretory multiple myeloma.

Staging and monitoring of multiple myeloma (MM) is mainly based on monoclonal component quantification; the absence of such a parameter renders difficult follow up of patients with nonsecretory MM (nsMM). In this study our aims were to determine the specificity and sensitivity of Tc99m-sestaMIBI scintigraphy at diagnosis and during follow up of nsMM patients. Nine nsMM patients were prospectively studied at diagnosis and during treatment for a mean time of 33 months (range: 12-65+). Tc99m-sestaMIBI (MIBI) scintigraphy was compared to conventional imaging (CI: X ray with CAT or NMR details) at diagnosis and during follow up. At diagnosis, CI and MIBI were concordant in three patients; CI showed more focal lesions than MIBI in four patients, while MIBI revealed more focal lesions than CI in two patients. During the follow up, MIBI uptake was normal in the four patients who achieved remission. Five patients did not achieve remission: CI and MIBI were concordant in three, while MIBI was falsely negative in two patients. In conclusion, Tc99m-sestaMIBI scintigraphy has high sensitivity (no false positive cases) and 78% specificity (2/9 false negative cases) in tracing active nsMM lesions; it should be considered complementary to CI for monitoring this rare disease.

Effects of cyclosporine on hematopoietic and immune functions in patients with hypoplastic myelodysplasia: in vitro and in vivo studies.

BACKGROUND: Immunosuppression may benefit some patients with hypoplastic myelodysplasia (HMDS) and refractory anemia (RA), but its mechanism of action is still obscure. METHODS: Using flow cytometry, we studied Fas-receptor (Fas-R), Fas-ligand (Fas-L), and interferon-gamma (IFN-gamma) expression in CD34(+) cells and lymphocytes obtained from 11 HMDS and 20 RA patients. In colony assays and long-term cultures, the effects of Fas triggering, IFN-gamma blockade, or cyclosporine(CsA) on the growth of hematopoietic progenitors (colony-forming cells [CFC]) were determined. The effects of CsA at daily doses of 1-3 mg/kg for at least 3 months in HMDS patients were also studied. RESULTS: In basal conditions, committed and immature progenitor cells were found decreased in myelodysplastic (MDS) patients. No significant differences between HMDS and RA patients were detected. IFN-gamma-expressing CD4(+) cells were significantly increased in HMDS patients, whereas intracytoplasmic Fas-L expression was only borderline elevated in CD3(+) MDS cells. Increased numbers of CD34(+) cells expressing Fas-R were found in HMDS and RA patients. CFC and secondary CFC showed higher susceptibility to Fas-L-mediated inhibition and the blockade of IFN-gamma improved marrow primary, but not secondary, CFC growth. CsA added in vitro to patient's lymphocytes significantly decreased the number of IFN-gamma-expressing CD4(+) cells, but not Fas-L production. These effects were associated with increased colony formation. Similar to IFN-gammablockade, production of secondary CFC was not enhanced by CsA. Administration of CsA to patients resulted in prolonged partial hematologic improvement in 8 of 11 HMDS patients. CONCLUSIONS: Increased frequency of IFN-gamma producing CD4(+) cells supports the involvement of lymphocyte-mediated suppression of hematopoiesis in the development of cytopenia in MDS patients. The ability of CsA to decrease in vitro IFN-gamma production may improve hematopoietic function, explaining the beneficial effect of this agent in HMDS patients.