Synchronous Bilateral Adrenalectomy for Cushing’s Syndrome: Laparoscopic Versus Posterior Retroperitoneoscopic Versus Robotic Approach

Background

Synchronous endoscopic bilateral adrenalectomy (BilA) can effectively provide definitive cure of hypercortisolism in ACTH-dependent Cushing’s syndrome and in primary adrenal bilateral disease. We compared three different approaches for BilA: transabdominal laparoscopic BilA (TL-BilA), simultaneous posterior retroperitoneoscopic BilA (PR-BilA), and robot-assisted BilA (RA-BilA).

Methods

All patients who underwent BilA between January 1999 and December 2012 at two referral centers (one performing TL-BilA and PR-BilA and one performing RA-BilA) were included. A comparative analysis was performed.

Results

Twenty-nine patients were included: 5 underwent TL-BilA, 11 underwent PR-BilA, and 13 underwent RA-BilA. No significant difference was found concerning age, gender, diagnosis, and previous abdominal surgery. No conversion to open approach was registered. Operative time was significantly shorter for the PR-BilA group than for the TL-BilA and RA-BilA groups (157.4 ± 54.6 vs 256.0 ± 43.4 vs 221.5 ± 42.2 min, respectively) (P < 0.001). No significant difference was found concerning intraoperative and postoperative complications rate and time to first flatus. Drains were used routinely after PR-BilA and TL-BilA and electively in four RA-BilA patients (P < 0.001). Hospital stay was longer in the TL-BilA and PR-BilA groups than in the RA-BilA group (12.0 ± 5.7 vs 10.8 ± 3.7 vs 4.4 ± 1.7 days, respectively) (P < 0.001). No recurrence or disease-related death was registered.

Conclusions

Operative time was significantly shorter in the PR-BilA group, because it eliminates the need to reposition the patient. The number of drains and the length of hospital stay were reduced after RA-BilA, but this was likely related to different management protocols in different settings. Because no significant difference was found in terms of postoperative outcome, none of the three operative approaches can be considered the preferable one.     

The Psychosocial Context Impacts Medication Adherence After Acute Coronary Syndrome

Background

Depression is associated with poor adherence to medications and worse prognosis in patients with acute coronary syndrome (ACS).

Purpose

To determine whether cognitive, behavioral, and/or psychosocial vulnerabilities for depression explain the association between depression and medication adherence among ACS patients.

Methods

One hundred sixty-nine ACS patients who agreed to have their aspirin adherence measured using an electronic pill bottle for 3 months were enrolled within 1 week of hospitalization. Linear regression was used to determine whether depression vulnerabilities predicted aspirin adherence after adjustment for depressive symptoms, demographics, and comorbidity.

Results

Of the depression vulnerabilities, only role transitions (beta?=??3.32; P?=?0.02) and interpersonal conflict (beta -3.78; P?=?0.03) predicted poor adherence. Depression vulnerabilities did not mediate the association between depressive symptoms and medication adherence.

Conclusions

Key elements of the psychosocial context preceding the ACS including major role transitions and conflict with close contacts place ACS patients at increased risk for poor medication adherence independent of depressive symptoms.     

Morbidity of central neck dissection: primary surgery vs reoperation. Results of a case–control study

Purpose

Complication rate in reoperative central neck node surgery is one of the main arguments to favor prophylactic central neck dissection at first operation in patients with papillary thyroid carcinoma. We evaluated if reoperative central neck dissection implies an increased postoperative morbidity. Secondarily, we aimed also to verify the effectiveness of the surgical resection of reoperative central neck dissection.

Methods

Forty-one patients who underwent reoperative central neck dissection after initial thyroidectomy for papillary thyroid carcinoma between January 2008 and May 2012 were compared to 41 controls who underwent central neck dissection at initial operation.

Results

The two groups were well matched for age, sex, and pN stage (P?=?0.296, 0.199, and 1.000, respectively). Three patients had distant metastases at presentation. No significant difference was found concerning mean number of removed nodes (P?=?0.064). No significant difference was found between the reoperative and the control groups concerning transient hypocalcemia (17 vs 19, respectively) (P?=?0.901) and transient recurrent nerve palsy (2 vs 2) (P?=?0.608). Follow-up was completed in 69 out of all the included patients (85.2 %). At a mean follow-up of 33 months, two patients (2.9 %) experienced nodal recurrence.

Conclusions

Morbidity of central neck dissection is similar for primary surgery and reoperation. In high-volume centers, reoperative central neck dissection can be safely accomplished when needed, allowing to achieve locoregional control in most of patients.     

Frequency of the HFE gene mutations in five Italian populations

Genetic hemochromatosis is an autosomal recessive disorder characterized by iron overload and a variety of clinical manifestations such as liver cirrhosis and arthropathy. It is the most common genetic disease of northern European populations. The principal gene responsible for hereditary hemochromatosis, designated HFE, is located on chromosome 6 in the HLA region. The single point mutation 845A, changing cysteine at position 282 to tyrosine (C282Y), in this gene has been identified as the main genetic basis of hereditary hemochromatosis. Two other mutations, 187G, a histidine to aspartate at amino acid 63 (H63D), and 193T, a serine to cysteine at amino acid 65 (S65C), appear to be associated with milder forms of hereditary hemochromatosis. There is a high prevalence of the C282Y mutation in northern European populations, whereas in those of the Mediterranean basin the prevalence seems low and almost absent in Far East countries. This mutation seems usually to occur on the ancestral haplotype 7.1. Accordingly, a Celtic origin of this mutation has been suggested. The aim of this study was to determine the frequency of HFE gene mutations in five geographic regions in Italy. Samples were tested for C282Y, H63D, and S65C mutations of the HFE gene according to methods of each laboratory and the results were standardized with the exchange of typed samples between the different laboratories. In addition, C282Y-positive DNA samples were typed for D6S105 allele 8 and HLA-A3 by ARMS-PCR. We have found that the allele frequency of the C282Y mutation decreases from northeast Italy (Friuli, 6%) to northwest Italy (Piedmont, 4.8%) and to central Italy (Emilia-Romagna, 1.7%). However, this mutation is lacking in the two regions of the Mediterranean basin's center (Sicily and Sardinia). Accordingly, a significant difference in the frequency of the mutation was observed between these Italian regions (P = 0.07 x 10(-3)). In contrast, no difference was observed in allele frequency of H63D in the five Italian regions. Finally, as regards the S65C mutation a very low frequency was observed in Friuli, Emilia-Romagna, and Sardinia, whereas in Sicily and Piedmont we have not found this mutation. In conclusion, these data are consistent with the hypothesis that the C282Y mutation occurred in Caucasian populations of Celtic origin, whereas the H63D mutation is more ancient as demonstrated by the ubiquitous distribution.     

B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo

Highly regulated activation of B cells is required for the production of specific antibodies necessary to provide protection from pathogen infection. This process is initiated by specific recognition of antigen through the B cell receptor (BCR), leading to early intracellular signaling followed by the late recruitment of T cell help. In this study we demonstrate that specific BCR uptake of CD1d-restricted antigens represents an effective means of enhancing invariant natural killer T (iNKT)-dependent B cell responses in vivo. This mechanism is effective over a wide range of antigen affinities but depends on exceeding a tightly regulated avidity threshold necessary for BCR-mediated internalization and CD1d-dependent presentation of particulate antigenic lipid. Subsequently, iNKT cells provide the help required for stimulating B cell proliferation and differentiation. iNKT-stimulated B cells develop within extrafollicular foci and mediate the production of high titers of specific IgM and early class-switched antibodies. Thus, we have demonstrated that in response to particulate antigenic lipids iNKT cells are recruited for the assistance of B cell activation, resulting in the enhancement of specific antibody responses. We propose that such a mechanism may operate to potentiate adaptive immune responses against pathogens in vivo.     

NGF and BDNF signaling control amyloidogenic route and Abeta production in hippocampal neurons

Here, we report that interruption of NGF or BDNF signaling in hippocampal neurons rapidly activates the amyloidogenic pathway and causes neuronal apoptotic death. These events are associated with an early intracellular accumulation of PS1 N-terminal catalytic subunits and of APP C-terminal fragments and a progressive accumulation of intra- and extracellular Aβ aggregates partly released into the culture medium. The released pool of Aβ induces an increase of APP and PS1 holoprotein levels, creating a feed-forward toxic loop that might also cause the death of healthy neurons. These events are mimicked by exogenously added Aβ and are prevented by exposure to β- and γ-secretase inhibitors and by antibodies directed against Aβ peptides. The same cultured neurons deprived of serum die, but APP and PS1 overexpression does not occur, Aβ production is undetectable, and cell death is not inhibited by anti-Aβ antibodies, suggesting that hippocampal amyloidogenesis is not a simple consequence of an apoptotic trigger but is due to interruption of neurotrophic signaling.