Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.

AIM: To determine the willingness of women with extremely dense breasts to undergo breast cancer screening with magnetic resonance imaging (MRI) in a research setting, and to examine reasons for women to participate or not. MATERIALS AND METHODS: Between 2011 and 2015, 8,061 women (50-75 years) were invited for supplemental MRI as part of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial (ClinicalTrials.gov Identifier: NCT01315015), after a negative screening mammography in the national population-based mammography screening programme. Demographics of participants and non-participants were compared. All invitees were asked to report reasons for (non)participation. Ethical approval was obtained. Participants provided written informed consent. RESULTS: Of the 8,061 invitees, 66% answered that they were interested, and 59% eventually participated. Participants were on average 54-years old (interquartile range: 51-59 years), comparable to women with extremely dense breasts in the population-based screening programme (55 years). Women with higher socio-economic status (SES) were more often interested in participation than women with lower SES (68% versus 59%, p<0.001). The most frequently stated reasons for non-participation were "MRI-related inconveniences and/or self-reported contraindications to MRI" (27%) and "anxiety regarding the result of supplemental screening" (21%). "Expected personal health benefit" (68%) and "contribution to science" (43%) were the most frequent reasons for participation. CONCLUSION: Of women invited for MRI because of extremely dense breasts, 59% participated. Common reasons for non-participation were "MRI-related inconveniences" and "anxiety regarding the result of supplemental screening". In case of future implementation, availability of precise evidence on benefits and harms might reduce this anxiety.

Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer.

Glioblastoma multiforme (GBM), the most frequent malignant brain tumor, has a poor prognosis, but is relatively sensitive to radiation. Both gemcitabine and its metabolite difluorodeoxyuridine (dFdU) are potent radiosensitizers. The aim of this phase 0 study was to investigate whether gemcitabine passes the blood-tumor barrier, and is phosphorylated in the tumor by deoxycytidine kinase (dCK) to gemcitabine nucleotides in order to enable radiosensitization, and whether it is deaminated by deoxycytidine deaminase (dCDA) to dFdU. Gemcitabine was administered at 500 or 1000 mg/m(2) just before surgery to 10 GBM patients, who were biopsied after 1-4 h. Plasma gemcitabine and dFdU levels varied between 0.9 and 9.2 microM and 24.9 and 72.6 microM, respectively. Tumor gemcitabine and dFdU levels varied from 60 to 3580 pmol/g tissue and from 29 to 72 nmol/g tissue, respectively. The gene expression of dCK (beta-actin ratio) varied between 0.44 and 2.56. The dCK and dCDA activities varied from 1.06 to 2.32 nmol/h/mg protein and from 1.51 to 5.50 nmol/h/mg protein, respectively. These enzyme levels were sufficient to enable gemcitabine phosphorylation, leading to 130-3083 pmol gemcitabine nucleotides/g tissue. These data demonstrate for the first time that gemcitabine passes the blood-tumor barrier in GBM patients. In tumor samples, both gemcitabine and dFdU concentrations are high enough to enable radiosensitization, which warrants clinical studies using gemcitabine in combination with radiation.

No evidence of gemcitabine accumulation during weekly administration.

Some anticancer agents tend to accumulate during repeated administration. We determined whether gemcitabine or its metabolites would accumulate during repeated administration. Gemcitabine was administered over two courses with each course consisting of a 30-min infusion at 1000 mg/m(2) weekly for 3 weeks followed by 1 week of rest. In 14 patients we evaluated eventual accumulation by comparing the concentrations in blood samples taken before, and at 30 and 60 min after the start of infusion on days 1, 8 and 15, in both cycles. At the end of the infusion gemcitabine concentrations at day 1 of both courses varied between 18 and 77 microM and at day 15 between 13 and 90 microM. The mean ratios day 8/day 1 and day 15/day 1 varied from 0.94 to 1.18. For the inactive metabolite 2',2'-difluoro-2'-deoxyuridine (dFdU) these values varied between 54 and 152 microM and 55 and 157, respectively, and the ratios from 0.96 to 1.08. The concentration of the active metabolite of gemcitabine, gemcitabine triphosphate (dFdCTP) in peripheral white blood cells, ranged between 37 and 283 pmol/10(6) cells at the end of infusion on day 1 and 35 and 115 pmol/10(6) cells on day 15. Potential accumulation was evaluated using a mixed effects model and no evidence was observed of accumulation for either gemcitabine or its metabolites. Gemcitabine can be administered safely without the risk that the drug will accumulate.

Phase II trial of cisplatin and gemcitabine in patients with advanced gastric cancer.

BACKGROUND: This phase II study was performed to determine the efficacy and toxicity of cisplatin and gemcitabine in patients with advanced gastric cancer. PATIENTS AND METHODS: Forty chemo-naïve patients with measurable locoregionally advanced or metastatic gastric cancer were included; the median patient age was 53 years (range 35-71). Cisplatin was administered at a dose of 50 mg/m2, given in 1 h intravenously (i.v.) on days 1 and 8, followed after 24 h by gemcitabine at a dose of 800 mg/m2 given in 30 min i.v. on days 2, 9 and 16, every 28 days. RESULTS: A median number of four therapy cycles were given (range 2-8). Myelosuppresion was the most important toxicity. Grade 3-4 thrombopenia was observed in 19 patients (48%) and grade 3-4 leukopenia was observed in 23 (58%). Myelotoxicity was cumulative and caused omission of gemcitabine on day 16 in 55% of cycles. Non-haematological toxicity consisted mainly of grade 1-2 nausea and vomiting. Objective responses were observed in 30% of patients including two complete remissions and 10 partial remissions. Median survival was 11 months (range 3-27+). CONCLUSIONS: This cisplatin-gemcitabine regimen had moderate efficacy in patients with advanced gastric cancer, with manageable toxicity. Further studies with this combination may be warranted.

[Too young for a twisted painful back]. / Te jong voor een pijnlijke scheve rug.

One girl aged 13 years and 2 boys aged 18 and 14 years had a painful scoliosis. Plain radiographs, blood tests and MRI revealed no abnormalities. Bone scintigraphy and CT scans were needed to establish the diagnosis 'osteoid osteoma'. In the girl, the initial CT scan was also negative and the tumours could only be found after using thin slices. She had had the complaints for 6 months and both boys had had the complaints for more than a year, before the diagnosis was made. They all made a complete recovery after surgical resection. A chronic painful back in young patients is often caused by structural deformities. The differential diagnosis also includes an osteoid osteoma. If an osteoid osteoma is suspected, then after radiographs, bone scintigraphy is indicated, which if necessary can be followed up with targeted CT scans.

Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer.

A feasibility study was performed to assess the toxicity and efficacy of a combination of gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer (LAPC). 24 patients (15 females and 9 males) with measurable LAPC were included; the median age of the patients was 63 years (range 39-74 years). The performance status ranged from 0 to 2. Gemcitabine was administered at a dose of 300 mg/m(2), concurrent with radiotherapy, three fractions of 8 Gy, on days 1, 8 and 15. When compliance allowed, gemcitabine alone was continued thereafter, at 1000 mg/m(2), weekly times 3, every 4 weeks, depending on the response and toxicity. All patients were evaluable for toxicity and response. The objective response rate was 29.2% (1 complete remission+6 partial remissions); 12 patients had stable disease. However, 2 of the radiological partial remissions were shown to be complete remissions by pathology assessment. Median duration of response was 3 months (range 1-35+months). Median time to progression was 7 months (range 2-37+months). Median survival was 10 months (range 3-37+months). Dose reduction or omission of gemcitabine was necessary in 10 patients. Non-haematological toxicity consisted of 87.5% nausea and vomiting grade I-II, diarrhoea 54%, ulceration in stomach and duodenum 37.5% (20.8% ulceration with bleeding); 1 patient developed a fistula between the duodenum and aorta, 5 months after treatment. Anaemia grade III-IV was observed in 8.3% of the patients. Neutropenia grade III-IV was observed in 8.3%, thrombocytopenia grades III-IV in 16.7%. In 1 patient who underwent resection postchemoradiation, no viable tumour cells were found. In addition, in the patient who suddenly died of a fistula between the duodenum and aorta, no viable tumour cells were detectable at autopsy. Although the toxicity of this treatment was occasionally severe, the response and survival are encouraging and warrant further studies of this combination.

Partridge osteosynthesis: a prospective clinical study on the use of nylon cerclage bands and plates in the treatment of periprosthetic femoral shaft fractures.

OBJECTIVE: To evaluate the clinical use of the Partridge osteosynthesis in periprosthetic femoral fractures. DESIGN AND SETTING: Prospective nonrandomized clinical study. PATIENTS: Over a ten-year period, 222 patients presenting with femoral fractures near the tip of a hip prosthesis were treated with the Partridge system, which employs elevated cerclage nylon bands and flexible elevated nylon plates. Sixty-five fractures were located cranial to the tip of the prosthesis (Whittaker Type I), 116 at the tip (type II), and forty-one distal to the tip of the prosthesis (Type III). The population consisted of 172 female and fifty male patients, with a mean age of 79.5 years. The mean duration between the index procedure and occurrence of the second fracture was 1.5 years. In 78 percent of the patients (173 out of 222), surgery was undertaken within forty-eight hours. Fracture reduction was open, and two nylon plates set at right angles to each other were secured to the femur with six to eight nylon bands. The mean operating time was fifty-five minutes, with an average blood loss of 550 milliliters. RESULTS: There were minor wound healing problems in eighteen patients (12.6 percent); there were no deep wound infections. Thirty-three elderly patients died within the first month from medical complications. Of the 189 remaining patients, 60 percent regained their prefracture functional level within six months postoperatively, whereas 25 percent required a higher level of care. The mean time of the in-hospital stay was thirty-three days. Ninety-three percent of the fractures consolidated with abundant callus during the follow-up period of one year. CONCLUSION: The indication for the use of this simple osteosynthesis method is swift convalescence by splinting the periprosthetic femoral fractures. Even with a loose prosthesis, the fracture often healed with abundant callus and the patient could be mobilized.

Acetabular fractures in children and adolescents.

A retrospective study of 29 acetabular fractures in children 2 to 16 years of age with an average followup of 14 years is presented. Nineteen patients had an additional dislocation of the femoral head and 14 patients had an associated neurologic injury. Surgical treatment was performed in 16 patients and consisted of open reduction and internal fixation in 14 patients and a simple arthrotomy in two patients. Thirteen patients were treated nonoperatively with traction or bedrest. The outcome was satisfactory in all patients with undisplaced fractures and fractures with disruption of a small fragment. Eight patients with linear fractures with instability all were treated surgically. All but one of the patients had a satisfactory functional outcome; one patient had early degenerative changes develop after an open pelvic and acetabular fracture. Patients with central fractures and dislocations had a relatively poor outcome, and congruency was achieved in only one of the four patients who were treated surgically. Results may deteriorate with time, as was seen when the results of the current study were compared with those published 10 years previously.

Randomized trial of radiofrequency lumbar facet denervation for chronic low back pain.

STUDY DESIGN: A prospective double-blind randomized trial in 31 patients. OBJECTIVES: To assess the clinical efficacy of percutaneous radiofrequency denervation of the lumbar zygapophysial joints in reducing pain, functional disability, and physical impairment in patients with back pain originating from the lumbar zygapophysial joints. SUMMARY OF BACKGROUND DATA: Chronic low back pain is a major health problem in the industrialized world. A treatment option is percutaneous radiofrequency denervation of the lumbar zygapophysial joints. Its clinical efficacy has never been formally tested in a controlled trial. METHODS: Thirty-one patients with a history of at least 1 year of chronic low back pain were selected on the basis of a positive response to a diagnostic nerve blockade and subsequently randomly assigned to one of two treatment groups. Each patient in the radiofrequency treatment group (15 patients) received an 80 C radiofrequency lesion of the dorsal ramus of the segmental nerve roots L3, L4, and L5. Patients in the control group (n = 16) underwent an the same procedure but without use of a radiofrequency current. Both the treating physician and the patients were blinded to the group assignment. Before treatment, physical impairment, rating of pain, the degree of disability, and quality of life were assessed by a blinded investigator. RESULTS: Eight weeks after treatment, there were 10 success patients in the radiofrequency group (n = 15) and 6 in the sham group (n = 16). The unadjusted odds ratio was 3.3 (P = 0.05, not significant), and the adjusted odds ratio was 4.8 (P < 0.05, significant). The differences in effect on the visual analog scale scores, global perceived effect, and the Oswestry disability scale were statistically significant. Three, 6, and 12 months after treatment, there were significantly more success patients in the radiofrequency group compared with the sham group. CONCLUSIONS: Radiofrequency lumbar zygapophysial joint denervation results in a significant alleviation of pain and functional disability in a select group of patients with chronic low back pain, both on a short-term and a long-term basis.

[Team care: a necessity for a child with HIV infection]. / Teamzorg: een noodzaak voor het met HIV geïnfecteerde kind.

In four children, a boy aged 2.5 years, a girl of 4, her brother of 7 years and a girl aged 10 months, HIV infection was diagnosed. Since 1996 HIV-infected children in the Netherlands are treated with a combination of two nucleoside analogs and a protease-inhibitor. This therapy improves the quality of life, increases the life expectancy of HIV-infected children and is generally well tolerated. However, the current combination therapy is complex and puts a burden on the child and the family. Therefore, long term compliance will be difficult. Moreover, the majority of the families have extremely difficult social circumstances which interfere with an optimal medical treatment for the child. The parents of three of the children were refugees from African countries. Intensive support of the family by a team of health care and social workers is usually necessary to make antiretroviral combination therapy possible. Care directed at the individual needs of the child and family is crucial to help this vulnerable group of children and families in our society.

Myocardial substrate uptake and oxidation during and after routine cardiac surgery.

OBJECTIVE: This study was designed to clarify whether myocardial substrate uptake and oxidation change after a period of hypothermic cardioplegic arrest during coronary artery bypass grafting procedures. METHODS: In 30 patients arterial and coronary sinus blood was sampled and coronary sinus flow measurements were performed before and after sternotomy and 10 minutes, 20 minutes, 50 minutes, and 6 hours after release of the aortic crossclamp. Measurement of free fatty acids, lactate, glucose, oxygen content, and carbon dioxide content in arterial and coronary sinus blood allowed calculations of myocardial substrate use, respiratory quotients, and myocardial oxidation rates of carbohydrates and fat. RESULTS: Uptake of free fatty acids and lactate was significant throughout the study and did not change in association with release of the crossclamp. Free fatty acid and lactate uptake measured 6 +/- 4 micromol/min and 23 +/- 26 micromol/min, respectively, before crossclamping compared with 8 +/- 7 micromol/min and 19 +/- 21 micromol/min, respectively, after release of the clamp. Glucose uptake was significant only during the first hour after crossclamp release and increased from 7 +/- 50 to 28 +/- 34 micromol/L after crossclamp release. Myocardial oxygen consumption did not change significantly (0.5 +/- 0.2 mmol/L compared with 0.35 +/- 0.2 mmol/L) after release of the crossclamp. Myocardial oxygen extraction ratio decreased from 58% +/- 8% to 41% +/- 13% after crossclamp release. Respiratory quotient increased after crossclamp release (0.85 +/- 0. 2 compared with 1.00 +/- 0.2), which implies that carbohydrate oxidation increased at the expense of free fatty acid oxidation. CONCLUSION: We conclude that hypothermic cardioplegic arrest during coronary artery bypass graft operations is associated with a transiently increased uptake and oxidation of carbohydrates during the immediate reperfusion phase.

Anatomical variations of the lateral femoral cutaneous nerve and the consequences for surgery.

PURPOSE: This two-part study was undertaken to (a) determine the course and variations of the lateral femoral cutaneous nerve in a cadaver study and (b) develop prospectively the preoperative protocol to diminish the possibility of a postoperative meralgia paresthetica; the latter was achieved by reviewing the patient series retrospectively for complaints of a lateral femoral cutaneous nerve (LFCN) lesion and by studying the relation of the course of the LFCN and meralgia paresthetica. METHODS: Anatomical studies were performed on 200 recently deceased patients. After exploring the LFCN from its origin to the inguinal region to determine its course, we classified 149 patients as "normal" and fifty-one as abnormal. We then identified eighty-two patients who, between 1989 and 1994, experienced LFCN lesion as a complication of pelvic surgery following an ilioinguinal approach. RESULTS: Thirty-seven of these patients reported altered sensation for several years postoperatively (minimum follow-up one year), including eleven patients whose complaints persisted. In five of these cases, symptoms prompted an eventual exploration of the nerve, and nerve entrapment was confirmed. Between 1994 and 1996, perioperative care intended to lessen the chance of future LFCN problems was administered to forty patients. Thirty-three patients underwent neurolysis, and seven underwent nerve transection because an LFCN lesion occurred during the operation. Within a twelve-month follow-up period, no meralgia paresthetica was noted. CONCLUSION: The practical importance of the present study lies in alerting the surgeon to a possible anatomical variation of the LFCN in about 25 percent of the patient population. It also confirms that the new perioperative protocol lowers the incidence of meralgia paresthetica.

[One hundred years of orthopedics in the Netherlands. II. Treatment of fractures]. / Honderd jaar orthopedie in Nederland. II. Fractuurbehandeling.

The treatment of fractures was originally conservative. Improvements in materials and surgical techniques and new insights into the biological aspects of fracture healing led to an increase of surgical treatment of fractures. The main breakthrough of osteosynthesis took place with the foundation of the Arbeitsgemeinschaft für Osteosynthesefragen (Study Group for Problems in Osteosynthesis) which had as its basic principles anatomical repositioning, stable internal fixation, atraumatic surgical technique and early mobilization. In general, surgical treatment is indicated for periarticular fractures, open fractures, fractures complicated by nervous or vascular lesions, pathological fractures and fractures in multiple injury patients. The question who should practise traumatology, the general or the orthopaedic surgeon, was initially a point of controversy; by now, cooperative teams have been formed based on appreciation of one another's qualities. The trend for the near future appears to be minimally invasive surgery, with indirect repositioning and fixation techniques and biological methods of stimulating fracture healing.

Effects of a single pre-operative dexmedetomidine dose on isoflurane requirements and peri-operative haemodynamic stability.

In a double-blind, placebo-controlled study we investigated the effect of a single pre-induction intravenous dose of dexmedetomidine 2 micrograms.kg-1 on anaesthetic requirements and peri-operative haemodynamic stability in 50 patients undergoing minor orthopaedic and general surgery. Patients were anaesthetised with nitrous oxide/oxygen/fentanyl, supplemented if necessary with isoflurane. The mean (SD) intra-operative isoflurane concentration was lower in the dexmedetomidine-treated patients than controls (0.01 (0.03)% compared to 0.1 (0.1)%; p = 0.001) although six of the 25 treated patients required isoflurane at some stage. The haemodynamic response to tracheal intubation and extubation was reduced in the dexmedetomidine group as was intra-operative heart rate variability; postoperative analgesic and anti-emetic requirements and peri-operative serum catecholamine concentrations were lower in the dexmedetomidine group. Hypotension and bradycardia occurred more frequently after dexmedetomidine.