Axillary ultrasonography in breast cancer patients helps in identifying patients preoperatively with limited disease of the axilla.

BACKGROUND: The sentinel lymph node biopsy (SLNB) procedure is the method of choice for the identification and monitoring of regional lymph node metastases in patients with breast cancer. In the case of a positive sentinel lymph node (SLN), additional lymph node dissection is still warranted for regional control, although 40-65 % have no additional axillary disease. Recent studies show that after breast-conserving surgery, SLNB, and adjuvant systemic therapy, there is no significant difference between recurrence-free period and overall survival if there are ≤2 positive axillary nodes. The purpose of this study was preoperative identification of patients with limited axillary disease (≤2 macrometastases) by using ultrasonography. METHODS: Data from 1,103 consecutive primary breast cancer patients with tumors smaller than 50 mm, no palpable adenopathy, and a maximum of 2 SLNs with macrometastases were collected. The variable of interest was US of the axilla. RESULTS: Of the 1,103 patients included, 1,060 remained after exclusion criteria. Of these, 102 (9.6 %) had more than 2 positive axillary nodes on ALND. Selected by unsuspected US, the chance of having >2 positive lymph nodes (LNs) is substantially lower (4.2 %). This is significant on univariate and multivariate analysis. After excluding the patients with extracapsular extension of the SLN, the chance of having >2 positive LNs is only 2.6 %. For pT1-2, this is 2.2 %. CONCLUSIONS: The risk of more than 2 positive axillary nodes is relatively small in patients with cT1-2 breast cancer. US of the axilla helps in further identifying patients with a minimal risk of additional axillary disease, putting ALND up for discussion.

The prognostic value of tumour-stroma ratio in triple-negative breast cancer.

BACKGROUND: Triple-negative cancer constitutes one of the most challenging groups of breast cancer given its aggressive clinical behaviour, poor outcome and lack of targeted therapy. Until now, profiling techniques have not been able to distinguish between patients with a good and poor outcome. Recent studies on tumour-stroma, found it to play an important role in tumour growth and progression. OBJECTIVE: To evaluate the prognostic value of the tumour-stroma ratio (TSR) in triple-negative breast cancer. METHODS: One hundred twenty four consecutive triple-negative breast cancer patients treated in our hospital were selected and evaluated. For each patient the Haematoxylin-Eosin (H&E) stained histological sections were evaluated for percentage of stroma. Patients with less than 50% stroma were classified as stroma-low and patients with ≥ 50% stroma were classified as stroma-high. RESULTS: Of 124 triple-negative breast cancer patients, 40% had a stroma-high and 60% had a stroma-low tumour. TSR was assessed by two investigators (kappa 0.74). The 5-years relapse-free period (RFP) and overall survival (OS) were 85% and 89% in the stroma-low and 45% and 65% in the stroma-high group. In a multivariate cox-regression analysis, stroma amount remained an independent prognostic variable for RFP (HR 2.39; 95% CI 1.07-5.29; p = 0.033) and OS (HR 3.00; 95% CI 1.08-8.32; 0.034). CONCLUSION: TSR is a strong independent prognostic variable in triple-negative breast cancer. It is simple to determine, reproducible and can be easily incorporated into routine histological examination. This parameter can help optimize risk stratification and might lead to future targeted therapies.

Percutaneous transvenous retrieval of intracardiac port-a-cath catheter fragment: a case report.

A female patient, 36 years of age, with a metastasised left breast cancer received several courses of chemotherapy for aggressive local tumour growth and multiple metastatic activity. In the current patient, surgical ablation of the left breast was carried out. Also loco-regional radio-therapy was conducted. To facilitate the administration of chemotherapy courses and prevent thrombophlebitis a vascular access port (port-a-cath) was surgically inserted via the right subclavian vein. After a few successful administrations of chemotherapeutic drugs the vascular port stopped functioning. It was demonstrated that a detached catheter fragment had dislodged into the right ventricle. Successful percutaneous, transvenous removal of the entrapped catheter fragment by the Gooseneck retrieval loop snare from the right ventricle was performed via the right femoral vein access. The procedure was uncomplicated and the patient tolerated the procedure well.

Dieting in children referred to the paediatric outpatient clinic.

UNLABELLED: Dietary interventions are sometimes necessary, even in young children; however, adhering to a diet can cause medical and psychosocial problems. Therefore, insight into frequency, reasons, and effectiveness is important. To establish the prevalence of dieting in children referred to a general paediatric outpatient clinic, parents of newly referred patients were given a structured questionnaire. Excluded were children whose parents did not speak Dutch, those younger than 3 months and emergency cases. Of 1826 patients, 907 (511 boys, 56%; median age 5 years, range 0-18 years) were included; 124 (13.7%, 95% CI 11.5%-15.9%) were or had been on a diet, more boys than girls (82/511 versus 42/396, P=0.02). In 60% of patients, the diet was started before the age of 2 years, 50% had been dieting longer than a year. Diets most used were: cow's milk free (62%), egg-free (20%), lactose-free (14%), no sugar (20%) and no colouring additives (20%). Reasons for dieting were gastrointestinal (51%), dermal (51%) and behavioural (27%) symptoms or complaints. Dieting was considered effective by the parents in 65% of cases and 61% reported no problems. CONCLUSION: One in eight children, referred to a general paediatric outpatient clinic is or has been dieting. Most parents reported positive effects with no problems. Some children were on a difficult-to-keep diet with serious medical and psychosocial implications, without being tested. Scientific evidence for dieting should be sought and the results discussed with the parents.

Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands.

OBJECTIVE: To study the incidence, signs and symptoms, diagnostic tests, risk factors, therapy, and complications of pediatric venous thromboembolism (VTE) in The Netherlands. METHODS: A prospective 2-year registry of VTE in children aged < or = 18 years. RESULTS: Ninety-nine patients were registered. The annual incidence of VTE was 0.14/10,000 children, 35% of whom were symptom free. Almost half of the patients were newborns. Neonatal VTE was almost exclusively catheter related, located in the upper venous system, and asymptomatic. In older children VTE was catheter related in approximately one third and more often was located in the lower venous system. In 85% of all patients, thrombosis developed while the patient was in the hospital. Diagnosis was usually made by ultrasonography. In 98% of all patients, at least 1 risk factor was present. Congenital prothrombotic disorders were more often present in older children (21%) than in neonates (6%). A variety of treatment modalities were used. Morbidity consisted of bleeding (7%) and recurrent thrombosis (7%). Two children died as result of VTE. CONCLUSION: VTE is mostly diagnosed in hospitalized children, especially sick newborns with central venous catheters and older children with a combination of risk factors. Primary prevention, optimal treatment, and long-term outcome of pediatric symptomatic and asymptomatic VTE need to be studied.

Are children with cystic fibrosis who are treated with a proton-pump inhibitor at risk for vitamin B(12) deficiency?

BACKGROUND: In a recent study, the authors demonstrated the beneficial effect of proton-pump inhibitors (PPI) on fat malabsorption and bone mineral content in children with cystic fibrosis (CF). Prolonged use of PPI could result in vitamin B(12) deficiency as a consequence of impaired release of vitamin B(12) from food in a nonacid environment. The aim of this study was to evaluate the vitamin B 12 status of CF patients either treated with a PPI or not by measuring vitamin B(12) and homocysteine blood levels, the latter being a sensitive indicator of vitamin B(12) deficiency. METHODS: The study population consisted of 20 CF patients, 11 patients treated with a PPI for at least 2 years and 9 patients not treated with a PPI, and 10 healthy, age-matched control participants. Homocysteine blood levels were measured by high-performance liquid chromatography, and vitamin B(12) levels were measured by a competitive protein-binding assay. RESULTS: Vitamin B(12) levels were significantly higher in both CF groups compared with the control participants (PPI+, P = 0.02; PPI-, P = 0.009). There was no significant difference in vitamin B(12) levels between both CF groups. Homocysteine levels were normal and similar in all groups. CONCLUSIONS: Cystic fibrosis patients treated with a PPI for at least 2 years show no signs of vitamin B(12) deficiency.

Nonlinear multiresolution signal decomposition schemes--part I: morphological pyramids.

Interest in multiresolution techniques for signal processing and analysis is increasing steadily. An important instance of such a technique is the so-called pyramid decomposition scheme. This paper presents a general theory for constructing linear as well as nonlinear pyramid decomposition schemes for signal analysis and synthesis. The proposed theory is based on the following ingredients: 1) the pyramid consists of a (finite or infinite) number of levels such that the information content decreases toward higher levels and 2) each step toward a higher level is implemented by an (information-reducing) analysis operator, whereas each step toward a lower level is implemented by an (information-preserving) synthesis operator. One basic assumption is necessary: synthesis followed by analysis yields the identity operator, meaning that no information is lost by these two consecutive steps. Several examples of pyramid decomposition schemes are shown to be instances of the proposed theory: a particular class of linear pyramids, morphological skeleton decompositions, the morphological Haar pyramid, median pyramids, etc. Furthermore, the paper makes a distinction between single-scale and multiscale decomposition schemes, i.e., schemes without or with sample reduction. Finally, the proposed theory provides the foundation of a general approach to constructing nonlinear wavelet decomposition schemes and filter banks.

Nonlinear multiresolution signal decomposition schemes--part II: morphological wavelets.

In its original form, the wavelet transform is a linear tool. However, it has been increasingly recognized that nonlinear extensions are possible. A major impulse to the development of nonlinear wavelet transforms has been given by the introduction of the lifting scheme by Sweldens (1995, 1996, 1998). The aim of this paper, which is a sequel to a previous paper devoted exclusively to the pyramid transform, is to present an axiomatic framework encompassing most existing linear and nonlinear wavelet decompositions. Furthermore, it introduces some, thus far unknown, wavelets based on mathematical morphology, such as the morphological Haar wavelet, both in one and two dimensions. A general and flexible approach for the construction of nonlinear (morphological) wavelets is provided by the lifting scheme. This paper briefly discusses one example, the max-lifting scheme, which has the intriguing property that preserves local maxima in a signal over a range of scales, depending on how local or global these maxima are.

Annular filters for binary images.

A binary annular filter removes isolated points in the foreground and the background of an image. Here, the adjective "isolated" refers to an underlying adjacency relation between pixels, which may be different for foreground and background pixels. In this paper, annular filters are represented in terms of switch pairs. A switch pair consists of two operators which govern the removal of points from foreground and background, respectively. In the case of annular filters, switch pairs are completely determined by foreground and background adjacency. It is shown that a specific triangular condition in terms of both adjacencies is required to establish idempotence of the resulting annular filter. In the case of translation-invariant operators, an annular filter takes the form X-->(X [plus sign in circle] A) [intersection] X [union or logical sum] (X [minus sign in circle] B), where A and B are structuring elements satisfying some further conditions: when A [intersection] B [intersection] (A [plus sign in circle] B) not equal Ø, it is an (idempotent) morphological filter; when A [union or logical sum] B [subset] A [plus sign in circle] B, it is a strong filter and in this case it can be obtained by composing in either order the annular opening X-->(X [plus sign in circle] A) [intersection] X and the annular closing X--> [union or logical sum] (X [minus sign in circle] B).

Rhizomelic chondrodysplasia punctata is a peroxisomal protein targeting disease caused by a non-functional PTS2 receptor.

Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal recessive disease characterized clinically by a disproportionately short stature primarily affecting the proximal parts of the extremities, typical dysmorphic facial appearance, congenital contractures and severe growth and mental retardation. Although some patients have single enzyme deficiencies, the majority of RCDP patients (86%) belong to a single complementation group (CG11, also known as complementation group I, Amsterdam nomenclature). Cells from CG11 show a tetrad of biochemical abnormalities: a deficiency of i) dihydroxyacetonephosphate acyltransferase, ii) alkyldihydroxyacetonephosphate synthase, iii) phytanic acid alpha-oxidation and iv) inability to import peroxisomal thiolase. These deficiencies indicate involvement of a component required for correct targeting of these peroxisomal proteins. Deficiencies in peroxisomal targeting are also found in Saccharomyces cerevisiae pex5 and pex7 mutants, which show differential protein import deficiencies corresponding to two peroxisomal targeting sequences (PTS1 and PTS2). These mutants lack their PTS1 and PTS2 receptors, respectively. Like S. cerevisiae pex cells, RCDP cells from CG11 cannot import a PTS2 reporter protein. Here we report the cloning of PEX7 encoding the human PTS2 receptor, based on its similarity to two yeast orthologues. All RCDP patients from CG11 with detectable PEX7 mRNA were found to contain mutations in PEX7. A mutation resulting in C-terminal truncation of PEX7 cosegregates with the disease and expression of PEX7 in RCDP fibroblasts from CG11 rescues the PTS2 protein import deficiency. These findings prove that mutations in PEX7 cause RCDP, CG11.

Composing morphological filters.

A morphological filter is an operator on a complete lattice that is increasing and idempotent. Two well-known classes of morphological filters are openings and closings. Furthermore, an interesting class of filters, the alternating sequential filters, is obtained if one composes openings and closings. This paper explains how to construct morphological filters, and derived notions such as overfilters, underfilters, inf-overfilters, and sup-underfilters by composition, the main ingredients being dilations, erosions, openings, and closings. The class of alternating sequential filters is extended by composing overfilters and underfilters. Finally, it is shown that any composition consisting of an equal number of dilations and erosions from an adjunction is a filter. The abstract approach is illustrated with some experimental results.

Dumping syndrome in a young child.

UNLABELLED: We describe a 17-month-old child with dumping syndrome after plication of the right diaphragm. He presented with periods of abdominal distension and pallor, recurrent convulsions, glucosuria and refusal of feeding. After changing the diet the symptoms disappeared. CONCLUSION: Although dumping syndrome in children is rare, early recognition is important. Serial determination of blood glucose after bolus feeding can lead to the diagnosis. Treatment should consist of dietary changes.

Late neurological, cognitive and behavioural sequelae of prenatal exposure to coumarins: a pilot study.

Neurological, cognitive and behavioural development were assessed in a group of 21, 8- to 10-year old children whose mothers took coumarins during pregnancy. Findings were compared with those in a group of 17 control children. The study was performed to test whether it is feasible to carry out a reliable retrospective study of late effects of prenatal exposure to coumarins. This turned out to be the case. In this small pilot study, no statistical significant differences were found between the study and control group, nevertheless a few findings were remarkable. One child showed severe neurological abnormalities, which may be due to prenatal exposure to oral anticoagulants. The children with the lowest scores on the neurological assessment and the lowest IQ-scores, were found in the exposed group. Obviously, the number of children in this study is too small to conclude if there has been definite effects from coumarin, but these results indicate that a large follow-up study is required. In the present paper, we have shown that such a study is feasible.

Intraoperative irradiation of the canine pancreas: short-term effects.

Intraoperative electron beam radiotherapy (IORT) is clinically used as a potential adjunctive treatment to surgery of locally advanced pancreatic and gastric cancer. The tolerance of the pancreas to IORT was studied in 15 adult beagles, divided in 3 groups of 5 beagles in which 25, 30 or 35 Gy IORT was delivered through a 6-7 cm circular lucite cone with 6-8 MeV electrons to the pancreas and medial wall of the duodenum. The dogs were followed for endocrine and exocrine pancreatic insufficiency. Two dogs (13%) developed radiation-induced morbidity which consisted of a common bile duct stenosis and an enterocolic fistula, as was confirmed at autopsy after 8 and 18 months, respectively. After a follow-up of 1 year, none of the dogs had developed pancreatitis, diabetes or exocrine insufficiency. There was a significant reduction in serum insulin levels and glucose clearance rates without overt diabetes for 30 Gy and 35 Gy (p < 0.05). No significant changes were found for 25 Gy. This study suggests that 25 Gy IORT to the pancreas may be used clinically, and that higher IORT doses may induce endocrine pancreatic insufficiency in the long-term.

Surgical treatment of Crohn disease in children and adolescents; how conservative can the paediatrician be?

Thirty-eight children (21 male, 17 female, age 3-18 years), treated for Crohn disease in two Dutch university centres, were retrospectively studied in order to evaluate the results of conservative treatment and to find out in what way surgical treatment in this age group may have differed from treating adults with this disease. Both groups had an equal distribution of age and sex. Diarrhoea with discharge of blood and mucus, abdominal pain, nausea/vomiting, weight loss, fever and general discomfort were the most frequent presenting symptoms. Twenty-three children (60%) showed signs of malabsorption; 4 children (10%) had growth retardation. In 27 children (70%), 63 surgical procedures were performed (2.4 operations per child). There was no surgical mortality. Most operations were performed for ileocolitis and colon-only localizations needed most re-operations. Of the surgical procedures performed, 55% were excisional procedures. Already 3 years after the onset of symptoms, 50% of all children had had their first resection, whereas in adults, 50% of the patients undergo surgery 8 years after disease onset. Eight children were treated with split ileostomy. In only one of these children, operated for non-toxic colitis and severe steroid-dependent growth retardation, could the colon eventually be saved. The time between the onset of symptoms and the first operation seems to be shorter in children compared to adults. Severe malabsorption and growth retardation are additional specific indications for surgery for Crohn disease in childhood. The latter combined with non-toxic colitis, may perhaps be the only indication left for performing split ileostomy in Crohn disease.