Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway

Tyrosinemia type 1 (TT1) and phenylketonuria (PKU) are both inborn errors of phenylalanine–tyrosine metabolism. Neurocognitive and behavioral outcomes have always featured in PKU research but received less attention in TT1 research. This study aimed to investigate and compare neurocognitive, behavioral, and social outcomes of treated TT1 and PKU patients. We included 33 TT1 patients (mean age 11.24 years; 16 male), 31 PKU patients (mean age 10.84; 14 male), and 58 age- and gender-matched healthy controls (mean age 10.82 years; 29 male). IQ (Wechsler-subtests), executive functioning (the Behavioral Rating Inventory of Executive Functioning), mental health (the Achenbach-scales), and social functioning (the Social Skills Rating System) were assessed. Results of TT1 patients, PKU patients, and healthy controls were compared using Kruskal–Wallis tests with post-hoc Mann–Whitney U tests. TT1 patients showed a lower IQ and poorer executive functioning, mental health, and social functioning compared to healthy controls and PKU patients. PKU patients did not differ from healthy controls regarding these outcome measures. Relatively poor outcomes for TT1 patients were particularly evident for verbal IQ, BRIEF dimensions “working memory”, “plan and organize” and “monitor”, ASEBA dimensions “social problems” and “attention problems”, and for the SSRS “assertiveness” scale (all p values <0.001). To conclude, TT1 patients showed cognitive impairments on all domains studied, and appeared to be significantly more affected than PKU patients. More attention should be paid to investigating and monitoring neurocognitive outcome in TT1 and research should focus on explaining the underlying pathophysiological mechanism

Morbidity after axillary sentinel lymph node biopsy in patients with cutaneous melanoma

Aim: In this study, the short-term and tong-term morbidity was assesed after axillary sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (SLNB/ALND) in patients with cutaneous melanoma. Methods: Between 1995 and 2003, 119 axillary SLNBs were performed for cutaneous melanoma. Fifty-eight patients met the inclusion criteria and entered the study. Results: Forty-four patients underwent SLNB alone and 14 patients underwent axillary lymph node dissection after positive SLNB. Complications after SLNB atone: post-operative bleeding (n = 2), seroma (n = 1) and slight lymphedema 11%. Complications after SLNB/ALND: wound infections (n = 2), seroma (n = 5) and slight lymphedema 7%. There were differences between the two groups in short-term complications (p <.001) and functional limitations of the shoulder (p = .011). Conclusion: Axillary SLNB atone had a tow complication rate. However, SLNB followed by completion ALND was associated with an increased risk of short- and long-term complications. (c) 2005 Elsevier Ltd. All rights reserved

Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma: three time periods at risk for amputation.

Item does not contain fulltextBACKGROUND: The aim of this study was to investigate the long-term limb salvage rate and overall survival after isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma (STS). METHODS: From 1991 to 2003, 73 patients (36 men, 37 women, median age 54 [range 14-80] years) with biopsy-proven STS underwent 77 perfusions followed by delayed surgical resection, with or without adjuvant radiation. Limb salvage and overall survival curves were calculated by the Kaplan-Meier method. RESULTS: A total of 21 amputations (28%) were performed. Overall 1, 5, and 10 years' limb salvage was 80.1% +/- 4.8%, 68.2% +/- 6.5%, and 60.6% +/- 9.2%, respectively. We found that the risk of amputation was linked to three time periods. The first was within a year after perfusion, mainly as a result of massive necrosis of the tumor and overlying skin, resulting in soft tissue deficit or recurrent disease (n = 17). The second was within 5 years, with two amputations performed for late local recurrence. The third occurred 10 years after perfusion, with two amputations performed for critical leg ischemia. Another two patients developed a pathological fracture of the femur due to radiation osteonecrosis. These four patients received adjuvant radiotherapy. Overall, 1, 5, and 10 years' survival was 82.9% +/- 9.2%, 58.7% +/- 13.1%, and 42.5% +/- 18.2%, respectively. CONCLUSIONS: ILP treatment with tumor necrosis factor alpha and melphalan followed by delayed surgical resection and adjuvant radiation treatment is an effective limb salvage treatment regimen for locally advanced STS. However, we observed late morbidity, with two amputations performed for critical leg ischemia and two pathological fractures of the femur in patients receiving adjuvant radiotherapy

Liver Cancer in Tyrosinemia Type 1

Hereditary Tyrosinemia type I (HT1) is clinically mainly characterised by severe liver disease. Most patients present in their first months of life with liver failure, but others can present later with issues of compensated cirrhosis, renal tubulopathy or acute intermittent porphyria. If patients survive the acute phase with liver failure or if they present later with compensated cirrhosis, they often develop hepatocellular carcinoma early but also later in life. The course of the disease changed after the introduction of 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC), which blocks the tyrosine degradation pathway at an earlier step. Therefore, the toxic products did not accumulate anymore and all clinical problems resolved. However, the risk (although clearly decreased) for developing liver cancer remained, especially if NTBC treatment is initiated late, a slow decrease of the tumor marker alpha-fetoprotein is seen or if the alpha-fetoprotein concentrations remain just above the normal range. A rise of alpha-fetoprotein in these HT1 patients is more or less pathognomonic for liver cancer. Although hepatoblastoma development occurs in HT1 patients, most HT1 patients develop hepatocellular carcinoma (HCC) or a mixed type of carcinoma consisting of HCC and hepatoblastoma. Due to the small risk of liver cancer development, screening for liver cancer (especially HCC) is still recommended in HT1 patients using regular measures of alpha-fetoprotein and imaging. Ultrasound is mostly the modality of choice for surveillance, because it is widely available, it does not use radiation and is noninvasive. When a suspicious lesion is present, the higher sensitivity of MRI could be used for characterization and staging of lesions. At this moment, no HCC development in pre-symptomatically treated patients is reported. These different situations could possibly indicate that NTBC can prevent the start of the development of HCC when initiated early, but can't stop the development of HCC if it is prescribed at a later stage, stressing the importance of early diagnosis.</p