A descriptive study of transthyretin amyloidosis in a tertiary hospital without a referral unit.

BACKGROUND AND OBJECTIVE: Transthyretin amyloidosis (ATTR) is a rare disease that is part of systemic amyloidosis and is life-threatening. It can affect all organs and systems, the most frequent being neurological and cardiac involvement. This study aims to detect possible ATTR cases and carry out a descriptive study of them. MATERIAL AND METHODS: Descriptive single-centre study carried out in a tertiary hospital, which included patients with suspected ATTR between September 2016 and January 2020. RESULTS: A total of 190 suspected ATTR patients were detected. The study includes 100 of these patients, as well as 10 relatives of patients in whom ATTR was detected in its genetic variant (ATTRv). In total, ATTRv was detected in 7 individuals (3 with a presymptomatic mutation of the disease), 16 patients with age-related ATTR and 31 individuals with unknown cardiac amyloidosis with the tests performed, which confirms the presence of this disease in non-endemic areas. CONCLUSIONS: ATTR is a disease that must be taken into account in the differential diagnosis of patients with heart failure with preserved LVEF, especially if associated with neurological symptoms.

Accuracy of Focal Laser Treatment Based on External Imaging (OCT) Using a Navigated Retinal Laser System - a Case Series.

Background The navigated laser photocoagulation system (NAVILAS®, OD-OS GmBH, Teltow, Germany) is a laser treatment device that provides navigated laser treatment of the retina based on a fundus image. The purpose of this study was to investigate the accuracy of laser treatment based on external optical coherence tomography (OCT) images - a new application of the device. Patients and Methods This retrospective case series evaluated the accuracy of laser spot placement in 7 eyes after using overlaid external OCT images for planning NAVILAS laser treatment. After a mean time of 33 days, a post-treatment OCT was obtained and compared with the pretreatment plan on the previous OCT. Laser spots touching or overlapping the planned 100 µm laser spots were classified as "match" and invisible laser spots as "laser spot not evolved". Results A total of 477 laser spots in 7 eyes were evaluated (mean: 68 spots per eye). Of all planned laser spots, 361 (75.7 %) were visible on post-treatment OCT. 58.7 % of these spots matched the pretreatment plan. Non-matching laser spots showed no uniform pattern of dislocation. Conclusions Planning navigated NAVILAS Laser treatment based on manually imported OCT images seems to be less accurate than planning with NAVILAS integrated imaging. These findings warrant further evaluation, not only regarding the recently installed automated picture importing tool but also concerning its clinical impact, which is possibly outweighed by the advantages of the additional image information.

Is liver biopsy necessary in the evaluation of a living donor for liver transplantation?

BACKGROUND: The role of liver biopsy in the evaluation of a candidate for living liver donation is controversial. Some authors suggest doing it routinely, but others do it only in selected cases. The aim of this work was to evaluate the usefulness of protocol liver biopsy in the evaluation of candidates for living liver donation. METHODS: Ninety potential candidates for living liver donation were evaluated. In 46 cases donation was contraindicated without the need of liver biopsy. In the remaining 44 candidates, liver biopsy was done on a protocol basis. The usefulness of protocol biopsy was compared with the use of biopsy according to the recommendations of the Vancouver Forum. RESULTS: Fifteen of the 44 biopsies were indicated according to the recommendations of the Vancouver Forum. Twelve of them were normal, and 3 had liver steatosis or steatohepatitis. Of the 29 biopsies done per protocol, 28 were normal and 1 showed liver steatosis. Donation was contraindicated according to liver biopsy findings in 3 of the 15 patients with liver biopsy done according to the Vancouver Forum recommendations and in none of the 29 patients with biopsy done per protocol (P = .034). CONCLUSIONS: Protocol liver biopsy has a limited utility in the evaluation of the candidates for living liver donation.

Efficacy of laparoscopic approach in the management of early liver transplant complications.

The use of the laparoscopic approach in managing early liver transplant complications has been shown to be safe and feasible in various settings with the advantages of shorter recovery period, decreased postoperative pain, and rapid functional recovery. The laparoscopic approach has been used to resolve postoperative complications in kidney and pancreas recipients and less often in orthotopic liver transplantation (OLT) recipients, most of them in the late period (> 1 month posttransplantation). We herein describe our experience with the laparoscopic management of early complications after liver transplantation. From May 2009 to May 2011, we successfully treated three patients with early abdominal complications after OLT using a laparoscopic approach. Three patients-two with intraabdominal bleedings and one with a small bowel obstruction were treated successfully, thereby avoiding risks of a relaparotomy. In addition to these benefits, the laparoscopic approach causes less tissue injury and consequently evokes a minor innate immune response.

Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma.

BACKGROUND: Occasionally, patients with hepatocellular carcinoma (HCC) who receive radioembolization with palliative intent are downstaged for radical treatments. The aim of this study was to describe and analyze the overall survival (OS) in these patients compared with patients of the same baseline stage (UNOS T3), who were not eligible for radical treatment after radioembolization. METHODS: Between September 2003 and August 2010, 118 patients with HCC received radioembolization with yttrium-90 ((90)Y) resin microspheres. Of these, 21 patients with UNOS T3 stage were retrospectively identified and included in this analysis. RESULTS: In total, 6 of 21 patients were downstaged and treated radically between 2 and 35 months post-radioembolization. Three patients were resected, 2 received liver transplantation and 1 was ablated and then resected. Patients treated radically were significantly younger (62 vs. 73 years, p = 0.006) and had higher tumor volume (583 mL vs. 137 mL, p = 0.001) than patients who did not achieve radical treatment. There were no differences between the groups in number of lesions, BCLC stage, previous cirrhosis, activity administered per tumor volume, or median levels of alpha-fetoprotein or total bilirubin. Across the whole series, the median OS was 27.0 months (95% CI 5.0-48.9), varying significantly between those treated radically (OS not reached after a median follow-up of 41.5 months since radical therapy) and those who received palliative treatment only (22.0 months; 95% CI 15.0-30.9). CONCLUSIONS: Radical therapy following tumor downstaging with radioembolization provides the possibility of long-term survival in a select subgroup (UNOS T3 stage) with otherwise limited options.

Portal revascularization in the setting of cavernous transformation through a paracholedocal vein: a case report.

Diffuse thrombosis of the entire portal system (PVT) and cavernomatous transformation of the portal vein (CTPV) represents a demanding challenge in liver transplantation. We present the case of a patient with nodular regenerative hyperplasia and recurrent episodes of type B hepatic encephalopathy concomitant with PVT as well as CTPV, successfully treated with orthotopic liver transplantation. The portal inflow to the graft was carried out through the confluence of 2 thin paracholedochal varicose veins, obtaining good early graft function and recovery of the encephalopatic episodes. This alternative should be kept in mind as an option to assure hepatopetal splanchnic flow in those cases of diffuse thrombosis and cavernomatous transformation of portal vein.

MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy.

OBJECTIVE: To describe a wide range of clinical and pathologic myopathic profiles associated with the p.K1729del mutation in the MYH7 gene, known to cause Laing distal myopathy. METHODS: A study conducted in the Safor region (Spain), setting of a large cluster of patients. Clinical, neurophysiologic, muscle imaging, and muscle biopsy studies and MYH7 gene sequencing were investigated in 32 patients from 4 kindreds. Data from 36 deceased or nonexamined patients were collected from hospital records or relatives. RESULTS: Onset ranged from congenital to the 6th decade. All patients presented weakness of great toe/ankle dorsiflexors and many had associated neck flexor, finger extensor, and mild facial weakness. In most cases, involvement of proximal and axial muscles was observed either clinically or by muscle imaging, sometimes giving rise to scapuloperoneal and limb-girdle syndromes. Disabling myalgias, skeletal deformities, and dilated cardiomyopathy in one patient were associated features. Life expectancy was not reduced but the spectrum of disability ranged from asymptomatic to wheelchair confined. Electromyographic neurogenic features were frequently recorded. Muscle fiber type disproportion, core/minicore lesions, and mitochondrial abnormalities were the most relevant pathologic alterations. All patients carried the p.K1729del mutation in MYH7. CONCLUSIONS: The p.K1729del mutation in the MYH7 gene expresses notable clinical variability and electromyographic and pathologic features that can lead to the misdiagnosis of neurogenic atrophies, congenital myopathies, or mitochondrial myopathies. Mutations in genes encoding other sarcomeric and reticulo-sarcoplasmic proteins involved in calcium regulation share pathologic characteristics with our patients, suggesting a possible pathogenetic connection.

Solid pseudopapillary tumor of the pancreas (SPPT). Still an unsolved enigma.

Solid pseudo-papillary tumor (SPPT) is a rare cystic tumor of the pancreas (1-3% of exocrine tumors of the pancreas) which shows an "enigmatic" behavior on the clinical and molecular pattern. A retrospective analysis of the cytological studies and resected specimens of pancreatic cystic tumors from May 1996 to February 2010 was carried out. Three cases of SPPT were found, which are the objective of this study. The diagnosis was established upon occasional finding in the abdominal CT, in spite of sizing between 3 and 6 cm of diameter. In the three cases the preoperative diagnosis was confirmed by cytology and specific immunohistochemical staining. Cases 2 and 3 showed strong immunoreactivity for Beta-Catenin and E-Cadherin staining. Radical resection (R0) was carried out in the three cases. A young male -21 years of age (case 1)- who had duodenal infiltration and two lymph nodes metastases died of hepatic and peritoneal recurrence 20 months following surgery. The other two cases are free of disease. The current review of the literature reports roughly 800 cases since the first report in 1959, and shows the enigmatic character of this tumor regarding the cellular origin, molecular pathways, prognostic factors and clinical behavior.

Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.

This comparative phase III trial of mitoxantrone+vinorelbine (MV) versus 5-fluorouracil+cyclophosphamide+either doxorubicin or epirubicin (FAC/FEC) in the treatment of metastatic breast cancer was conducted to determine whether MV would produce equivalent efficacy, while resulting in an improved tolerance in relation to alopecia and nausea/vomiting. This multicentre study recruited and randomised 281 patients with metastatic breast cancer; 280 were evaluable for response survival and toxicity (138 received FAC/FEC, 142 received MV). Patient characteristics were matched in each arm and stratification for prior exposure to adjuvant therapy was made prospectively. The overall response rate (ORR) was equivalent in the two arms (33.3% for FAC/FEC versus 34.5% for MV), but MV was more effective in patients who had received prior adjuvant therapy (13% (95% confidence interval (CI) 3-23) for FAC/FEC versus 33% (95% CI 20-47) for MV P=0.025) with a better progression-free survival (PFS) (5 months (range 1-18 months) versus 8 months (range 1-27 months); P=0.0007 for FAC/FEC versus MV, respectively) while FAC/FEC was more effective in previously untreated patients (ORR 43% (95% CI 33-53) versus 35% (95% CI 25-45), P=0.26; PFS 9 months (range 0-29 months) versus 6 months (range 0-26 months) P=0.014). Toxicity was monitored through the initial six cycles of therapy; febrile neutropenia and delayed haematological recovery was more frequent for MV (P=0.001), while nausea/vomiting of grades 3-4 was greater for FAC/FEC (P=0.031), as was alopecia (P=0.0001), cardiotoxicity was the same for the two regimens. MV represents a chemotherapy combination with equivalent efficacy to standard FAC/FEC and improved results for patients who have previously received adjuvant chemotherapy. Toxicity must be balanced to allow for increased haematological suppression and risk of febrile neutropenia with MV compared with a higher risk of subjectively unpleasant side-effects such as nausea/vomiting and alopecia with FAC/FEC.

An embryonic demethylation mechanism involving binding of transcription factors to replicating DNA.

In vertebrates, transcriptionally active promoters are undermethylated. Since the transcription factor Sp1, and more recently NF-kappaB, have been implicated in the demethylation process, we examined the effect of transcription factors on demethylation by injecting in vitro methylated plasmid DNA into Xenopus fertilized eggs. We found that various transactivation domains, including a strong acidic activation domain from the viral protein VP16, can enhance demethylation of a promoter region when fused to a DNA binding domain which recognizes the promoter. Furthermore, demethylation occurs only after the midblastula transition, when the general transcription machinery of the host embryo becomes available. Nevertheless, transcription factor binding need not be followed by actual transcription, since demethylation is not blocked by alpha-amanitin treatment. Finally, replication of the target DNA is a prerequisite for efficient demethylation since only plasmids that carry the bovine papilloma virus sequences which support plasmid replication after the midblastula transition are demethylated. No demethylation is detectable in the oocyte system where DNA is not replicated. These results suggest that, in the Xenopus embryo, promoters for which transcription factors are available are demethylated by a replication-dependent, possibly passive mechanism.

[Acute pancreatitis and diagnostic and therapeutic endoscopic retrograde cholangiopancreatography]. / Pancreatitis aguda y pancreatocolangiografía endoscópica retrógrada diagnóstica y terapéutica.

Urgent endoscopic retrograde cholangiopancreatography in acute pancreatitis allows to detect associated biliary disease, display the bilio-pancreatic anatomy to plan optional early surgery and offer an alternative in the treatment with endoscopic sphincterotomy and/or infundibulotomy, in cases of choledocholithiasis and impacted stone at the ampulla of Vater. In relation to the prevalence of biliary lesions in the etiology of acute pancreatitis, the urgent ERCP is a safe and useful procedure that offer diagnosis and treatment, so therefore, it must be considered during the evaluation of patients with acute pancreatitis.