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.     

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.     

Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82Rb PET/CT in predicting lesion-related outcome

European Journal of Nuclear Medicine and Molecular Imaging - Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC),...     

Selective Inhibition of Ii-dependent Antigen Presentation by Helicobacter pylori Toxin VacA

A major virulence factor in the stomach chronic infection by Helicobacter pylori is a protein toxin (VacA), which alters cell membrane trafficking of late endosomal/prelysosomal compartments. Its role in the chronic infection established by H. pylori is unknown. To test the possibility that VacA alters antigen processing taking place in prelysosomal compartments, we have used the well-established model of antigen processing and presentation consisting of tetanus toxoid–specific human (CD4⁺) T cells stimulated by autologous antigen-pulsed Epstein-Barr virus-transformed B cells. We found that VacA interferes with proteolytic processing of tetanus toxin and toxoid and specifically inhibits the Ii-dependent pathway of antigen presentation mediated by newly synthesized major histocompatibility complex (MHC) class II, while leaving unaffected the presentation pathway dependent on recycling MHC class II. The results presented here suggest that VacA may contribute to the persistence of H. pylori by interfering with protective immunity and that this toxin is a new useful tool in the study of the different pathways of antigen presentation.More than 50% of the world population is infected with Helicobacter pylori, but most infections remain asymptomatic and only 10% of infected people become sick at some point in their life (1, 2). A close correlation has been established between the prolonged infection of the human stomach mucosa by H. pylori and the development of gastritis, and gastroduodenal ulcers, and with an increased risk of developing adenocarcinomas and other gastric tumors (1–3). In fact, H. pylori has been classified as a class I cancerogenic agent, being one of the factors involved in the development of stomach cancers. This bacterium enters the mucus layer covering the stomach epithelium and colonizes the human gastric mucosa: such infection may persist for decades. Bacterial factors necessary for colonization (for review see reference 1) are the flagella, which make this bacterium highly motile, adhesins, which strongly bind the saccharide moiety of glycoproteins and glycolipids, and a powerful urease, which buffers the acid stomach environment by releasing ammonia. Biopsies from patients affected by gastroduodenal ulcers almost invariably contain H. pylori strains harboring a pathogenicity island (4), characterized by the presence of the gene encoding for the 128-kD CagA protein, the major H. pylori antigen. Such strains also produce a 145-kD precursor that is processed and released in the culture medium as a 95-kD protein toxin (VacA), whose role in H. pylori infection is unknown (5).VacA perturbs endocytosis at a prelysosomal stage in a process requiring the activity of the small GTPase Rab7 (6). This causes the formation and accumulation of compartments endowed with the vacuolar ATPase and with membrane markers both of late endosomes and lysosomes (6–8). In particular, the presence of Rab7 and lysosomal membrane glycoproteins, and the parallel absence of the cation-independent mannose 6-P receptor, allows the identification of those vesicles as an intermediate between late endosomes and lysosomes (7). A similar profile of markers is present in the compartments of APCs, where antigen proteolytic processing takes place (for review see reference 9).Here, we have considered the possibility that VacA inhibits antigen processing by interfering with late endocytic membrane trafficking by APCs. This would in turn lower the proliferation of autologous human (CD4⁺) T cells triggered by recognition of antigenic epitopes bound to MHC class II molecules exposed on APC surfaces (10). We have used the well-defined cellular system of antigen processing and presentation consisting of human tetanus toxoid (TT)– specific (CD4⁺) T cells stimulated by autologous antigen-pulsed EBV-transformed B cells (10). TT is the most used human vaccine and its proteolytic processing and presentation by human lymphoid cells in culture has been intensively investigated (10–13). By using T cell clones with different specificity, we found that VacA interferes with the generation of T cell epitopes loaded on newly synthesized MHC class II molecules (the Ii-dependent pathway of antigen presentation), leaving unaffected generation and presentation of epitopes by class II molecules that recycle through early endosomal compartments (invariant chain [Ii]–independent pathway).