High Hereditary Transthyretin-Related Amyloidosis Prevalence in Crete: Genetic Heterogeneity and Distinct Phenotypes.

Background and Objectives: Our goal was to study hereditary transthyretin-related amyloidosis (hATTR) in Crete, Greece. Methods: We aimed at ascertaining all hATTR cases in Crete, an island of 0.62 million people. For this, we evaluated patients with polyneuropathy, autonomic involvement, cardiomyopathy, and/or ophthalmopathy suggestive of hATTR, who presented to the physicians of this study or were referred to them by other physicians. Genetic analyses were performed on all patients suspected of suffering from hATTR. We included in our observational longitudinal cohort study all individuals, residents of Crete, who, during the study period (1993-2019), were found to carry a pathogenic TTR variant. Results: Over the past 27 years, 30 individuals (15 female patients, 15 male patients), from 12 apparently unrelated families, were diagnosed with hATTR, whereas evaluation of their offspring identified 5 asymptomatic TTR pathogenic variant carriers. The most prevalent TTR variant detected was p.Val50Met, affecting 19 patients (11 female patients, 8 male patients) and causing a rather consistent phenotype characterized by predominant polyneuropathy of early adult onset (median age of symptom onset: 30 years; range: 18-37 years). Specifically, patients affected by the p.Val50Met TTR variant experienced progressive sensorimotor disturbances, involving mainly the lower extremities, associated with autonomic and/or gastrointestinal dysfunction. The second most frequent TTR variant was p.Val114Ala, found in 10 patients (4 female patients, 6 male patients) who were affected at an older age (median age of symptom onset: 70 years; range: 54-78 years). This variant caused a predominantly cardiomyopathic phenotype, manifested by congestive heart failure and associated with peripheral neuropathy, carpal tunnel syndrome, and/or autonomic involvement. In these patients, cardiac amyloid deposition was detected on 99m-technetium pyrophosphate scintigraphy and/or heart biopsy. The third TTR variant (p.Arg54Gly) was found in a 50-year-old male patient with ophthalmopathy due to vitreous opacities and positive family history for visual loss. As 22 patients were alive at the end of the study, we calculated the hATTR prevalence in Crete to be 35 cases per 1 million inhabitants. Discussion: Our study revealed that the prevalence of hATTR in Crete is one of the world's highest. Three different pathogenic TTR variants causing distinct clinical phenotypes were identified in this relatively small population pool.

Screening for Hepatopulmonary Syndrome in Cirrhotic Patients Using Technetium 99m-macroaggregated Albumin Perfusion Lung Scan (Tc-MAA): Diagnostic Approach and Clinical Correlations.

BACKGROUND AND AIMS: The aims of this study were to prospectively screen cirrhotic patients with arterial blood gas test and albumin perfusion scan, identify those fulfilling the classic hepatopulmonary syndrome (HPS) criteria, correlate with clinical parameters, and evaluate the survival of patients with HPS compared with those without HPS in a genetically homogenous Cretan cirrhotic population. MATERIALS AND METHODS: Data on consecutive 102 patients within 1 year were collected and analyzed. All patients underwent a technetium 99m-macroaggregated albumin perfusion lung scan (Tc-MAA). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA≥6% and a [P(A-a)O2]≥15 mm Hg (≥20 mm Hg for patients over >64 y). RESULTS: In 94/102 patients, complete scintigraphic data were available. In total, 24 (26%) patients fulfilled the diagnostic criteria of HPS; 95.8% of them had mild-to-moderate HPS. In 8 patients the Tc-MAA scintigraphy could not be interpreted. There was no difference in HPS between decompensated (24.6%) and compensated cirrhosis (27.3%). In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS (P=0.001, odds ratio; 95% confidence interval, 7.05; 2.27-21.87). Kaplan- Meier survival curves indicated a similar overall prognosis for patients diagnosed with HPS (P=0.105). CONCLUSIONS: HPS is a frequent complication of cirrhosis. Mild-to-moderate HPS has no significant effect on survival of cirrhotic patients. The quantitative Tc-MAA test is a reliable tool for diagnosis.

Rare presentation of occult medullary carcinoma of the thyroid as a mediastinal mass.

OBJECTIVE: To describe a rare case of occult (<1 cm in diameter) medullary thyroid carcinoma (MTC) in a 45-year-old woman, presenting as an asymptomatic mediastinal mass. DESIGN: The diagnostic methodology included laboratory measurements of relevant biochemical and hormonal parameters including calcitonin (CT), carcinoembryonic antigen (CEA) and chromogranin A, and imaging techniques including ultrasound (U/S), computed tomography (C/T), magnetic resonance imaging (MRI) and radio labeled somatostatin analog ((111)In-DTPA-octreotide). RESULTS: Chest CT revealed a mediastinal mass measuring 5 cm in diameter abutting the right thyroid lobe. CEA was elevated and an association with thyroid malignancies was considered. CT was found to be markedly elevated, pointing to the diagnosis of MTC metastatic to the mediastinum. The patient underwent total thyroidectomy, lymph node dissection and removal of the mediastinal mass. Histological examination revealed MTC of the right thyroid lobe measuring 0.5 cm, metastatic to regional and superior mediastinal lymph nodes. CONCLUSIONS: Occult MTC can infrequently present as an asymptomatic mediastinal mass. Elevated serum CT and CEA along with imaging techniques leads to the correct diagnosis and surgical management of the disease.

Myocardial sympathetic innervation in patients with impaired glucose tolerance: relationship to subclinical inflammation.

AIM: This study was designed to assess cardiac adrenergic nerve activity, using iodine (I)-123-labeled metaiodobenzylguanidine (MIBG), in patients with impaired glucose tolerance (IGT) and to investigate its relation to circulating levels of proinflammatory cytokines. METHODS: We studied 22 patients with IGT (aged 34-68 years) and 18 age-matched healthy controls, using I-123 MIBG cardiac imaging. The early (10 min) and late (4 h) heart to mediastinum MIBG uptake (H/M) ratio and washout were calculated. Levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), and its soluble receptor [soluble TNF receptor II (sTNFRII)] were measured by immunoassay of blood samples from patients and controls. RESULTS: The early and late MIBG uptake was lower (both P<.001) and the WR was higher (P<.001) in patients than in controls. The analysis showed innervation defects in 20 of the 22 patients. Nearly half (45.4%) showed severe adrenergic innervation defects in both the inferior wall and the apex. Regarding cytokines, patients showed significantly elevated TNF-a (P=.005), sTNFRII (P<.001), and IL-6 (P<.001) levels compared to controls. IL-6 and sTNFRII were found to correlate with the WR (r=0.468, P=.028 and r=0.455, P=.034, respectively). CONCLUSION: Patients with IGT show reduced MIBG cardiac uptake with a segmental pattern. The reduced cardiac sympathetic innervation was related to the elevated proinflammatory cytokine levels and could be considered an index of early atherosclerotic process in these patients.

Sleeve gastrectomy: a restrictive procedure?

BACKGROUND: Diet and surgically-induced weight loss have been shown to lead to alterations in motor and sensory function of the stomach. We investigated the clinical outcome and gastric emptying of solid foods in morbidly obese (MO) patients following sleeve gastrectomy (SG). METHODS: We studied 23 MO patients [(7 males, 16 females), mean age 38.9 +/- 11.0 years (range 20-64 years), mean weight 135.1 +/- 19.0 kg (range 97-167 kg), mean BMI 47.2 +/- 4.8 kg/m(2) (range 39.6-56.0 kg/m(2))] who each underwent a sleeve gastrectomy (SG) for weight reduction. At the monthly follow-up visits, variations in weight and BMI changes, postoperative meal size and frequency, and presence of gastrointestinal symptoms were recorded. 11 patients underwent scintigraphic measurement of the gastric emptying of a solid meal pre- and 6 months postoperatively. RESULTS: A significant reduction in patients' weight was evidenced at 6 and 12 months postoperatively [98.6 +/- 11.8 kg and 87.0 +/- 10.7 kg respectively (P=0.001)]. BMI decreased to 35.2 +/- 4.3 kg/m(2) at 6 months and to 31.1 +/- 4.5 kg/m(2) at 12 months, respectively (P=0.001). Although meal size was drastically reduced, meal frequency increased postoperatively in 12 patients (52.2%). Only 5 patients (21.8 %) reported occasional vomiting after meals following SG. The gastric emptying half-time (T1/2) accelerated (47.6 +/- 23.2 vs 94.3 +/- 15.4, P<0.01) and the T-lag phase duration decreased (9.5 +/- 2 min vs 19.2 +/- 2 min, P<0.05) post-operatively. The percentage of the meal emptied from the stomach 90 min after consumption increased significantly after SG (75.4 +/- 14.9% vs 49.2 +/- 8.7%, P<0.01). CONCLUSIONS: This study indicates that following SG, the stomach empties its contents rapidly into the small intestine and symptoms of vomiting after eating (characteristic of restrictive procedures) are either absent or very mild. Therefore, the term 'restrictive' is possibly ill-advised for this new bariatric operation. It remains for other mechanisms of energy intake reduction, such as intestinal distension and satiety signals through gut hormones to be investigated, to comprehensively explain precisely how this 'food limiting' procedure results in weight loss.

Preoperative radionuclide lymphangiography and sentinel node localization with radionuclide techniques. Advantages and ambiguous aspects.

Axillary lymph node status is one of the most important prognostic factors for patients with melanoma and early breast cancer. Axillary lymph node dissection is an important part of the surgical treatment of breast cancer. As an alternative to axillary node dissection was proposed the sentinel lymph node detection (SLND). This technique was initially described for detecting occult lymph node metastasis in patients with melanoma and recently is used for breast cancer patients. Nowadays the radioisotopique techniques, including the lymphoscintigraphy and the intraoperative detection of SN, have received attention as a possible alternative to axillary lymph nodes dissection because of the clinical value of SN in malignancies and the development of technical equipment. We review the different techniques of preoperative lymphoscintigraphy and intraoperative detection of SN, including the radioisotopique tracers, timing and site of injection and the clinical value of both methods in patients with early breast cancer.