ABSTRACT: Currarino syndrome (CS) is a triad consisting of partial sacral agenesis, presacral mass, and anorectal malformations, typically anal stenosis but the phenotype varies. The main cause of this monogenic disorder is mutations in the motor neuron and pancreas homeobox 1 gene. We describe the clinical and genetic findings in 4 unrelated Swedish cases with CS and their relatives.
We performed mutation analysis of the motor neuron and pancreas homeobox 1 gene in 4 cases with CS by DNA sequence analysis as well as multiplex ligation-dependent probe amplification. In addition, array comparative genome hybridization was performed in 2 cases. Including relatives, totally, 14 individuals were analyzed.
We found 2 previously described mutations, 1 de novo nonsense mutation (p.Gln212X) and 1 maternally inherited frameshift mutation (p.Pro18ProfsX38). In the family with the frameshift mutation, we also detected the same maternally inherited mutation in 3 of the proband's 4 brothers, who displayed varying symptoms. All mutation carriers had presacral tumors, although 2 were asymptomatic.
Our findings emphasize the need for genetic counseling and mutation analysis in patients with CS to detect tumors early. It shows the importance of evaluation of the sacrum and the presacral region in patients with anal stenosis with or without funnel anus. Family members of index cases should be considered for evaluation even if they are asymptomatic.
Journal of Pediatric Surgery 07/2011; 46(7):1390-5. · 1.45 Impact Factor
ABSTRACT: Patients with locally advanced rectal cancer have a poor prognosis and the early and late postoperative morbidity is high. The aim of this study was to assess health-related quality of life (HRQL) in patients treated with extensive surgical resections for locally advanced rectal cancer and to compare the results with those in patients treated for primarily resectable rectal cancer.
Between 1991 and 2003, 142 patients with locally advanced rectal cancer had an extensive resection at the Karolinska Hospital in Stockholm, Sweden. A HRQL assessment with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR38 questionnaires was performed in patients alive and disease free in 2005. The results were compared with an age- and sex-matched reference group of patients with primarily resectable rectal cancer having had total mesorectal excision alone.
The study group of 43 patients (81% of eligible) scored clinically and statistically significantly lower in global quality of life, role function, physical function, social function, and body image and reported a higher degree of pain and fatigue compared with the reference group of 80 patients. In the study group, men scored lower than women in global quality of life, role functioning and social functioning and reported more problems with fatigue.
Several aspects of HRQL are impaired in disease-free patients treated for locally advanced rectal cancer. This knowledge may be useful in the preoperative counselling and postoperative support of these patients.
Annals of Surgical Oncology 09/2008; 15(11):3109-17. · 4.17 Impact Factor
ABSTRACT: Magnetic resonance imaging (MRI) is used for preoperative local staging in patients with rectal cancer. Our aim was to retrospectively study the effects of the imaging protocol on the staging accuracy.
MR-examinations of 37 patients with locally advanced disease were divided into two groups; compliant and noncompliant, based on the imaging protocol, without knowledge of the histopathological results. A compliant rectal cancer imaging protocol was defined as including T2-weighted imaging in the sagittal and axial planes with supplementary coronal in low rectal tumors, alongside a high-resolution plane perpendicular to the rectum at the level of the primary tumor. Protocols not complying with these criteria were defined as noncompliant. Histopathological results were used as gold standard.
Compliant rectal imaging protocols showed significantly better correlation with histopathological results regarding assessment of anterior organ involvement (sensitivity and specificity rates in compliant group were 86% and 94%, respectively vs. 50% and 33% in the noncompliant group). Compliant imaging protocols also used statistically significantly smaller voxel sizes and fewer number of MR sequences than the noncompliant protocols
Appropriate MR imaging protocols enable more accurate local staging of locally advanced rectal tumors with less number of sequences and without intravenous gadolinium contrast agents.
World Journal of Surgical Oncology 02/2008; 6:89. · 1.12 Impact Factor