Median Time Span Research Articles

Brain Tumors in Children: Initial Symptoms and Their Influence on the Time Span Between Symptom Onset and Diagnosis

Brain tumors are the most common solid tumor entity in childhood. Symptoms are often unspecific, depending not only on the localization of the tumor, but also on the age of the child. The aim of this study was to detect factors influencing the time span between the occurrence of symptoms and the diagnosis to alert health professionals to the early symptoms of pediatric brain tumors. The records of 245 consecutive patients treated for brain tumors between 1980 and 2004 at the neuropediatric department of the University of Muenster were analyzed regarding their primary symptoms, tumor location, entity, and, in 151 cases, the primary electroencephalogram findings. The median time span between symptom onset and diagnosis in our study was 24 days. Multivariate analysis showed a significant influence of 6 parameters on the interval between symptom onset and diagnosis. An additional symptom had a significant influence on the time span between symptom onset and diagnosis in the univariate analysis. The findings that several symptoms influence the interval between symptom onset and diagnosis emphasize the necessity to systematically inquire about the key symptoms of brain tumors. The challenge for every consultant is to decide in which cases cerebral imaging is appropriate. As the most frequent symptoms are unspecific and often underestimated, a detailed anamnesis is crucial to detect possible brain tumor patients. In doubtful cases, a systematic interrogation regarding the catalogue of symptoms can be helpful.

Retransplantation with stem cells from mismatched related donors after graft rejection in pediatric patients

Graft failure is a life-threatening complication after transplantation of hematopoietic stem cells. We report a cohort of 11 pediatric patients with leukemias ( n = 8) and severe aplastic anemia ( n = 3) who experienced graft rejection after myeloablative transplantation from mismatched related donors ( n = 6) or after cord blood or matched unrelated donor transplantation ( n = 5). In the latter, the original donor was not available anymore. All patients were re-transplanted with CD34 + selected or CD3/CD19 depleted stem cells from a second, haploidentical donor. Median time span from diagnosis of rejection to second transplant was 9 days. Reconditioning regimens comprised total lymphoid irradiation, thiotepa, fludarabine, ATG/OKT3 and were well tolerated. A median number of 23.5 × 10 6/kg stem cells with 95,000/kg residual T-cells were infused. Sustained engraftment of neutrophiles/platelets and complete donor chimerism was achieved in all patients (ANC > 500/μl: 9 (11–32) days). No GvHD > grade II was observed. 8/11 patients are disease free (median follow up 1.9 years; 1 year-EFS = 72%). Causes of death were: pneumonitis, infection, relapse. Thus, haploidentical transplantation represents a realistic option to rescue patients with graft failure within a short time span, for whom a second donation from the original donor is not available. The use of different donors may contribute to avoid a second rejection.

Fiberoptic ductoscopy combined with cytology testing in the patients of spontaneous nipple discharge

Fiberoptic ductoscopy system (FDS) offers a safe alternative to ductography in diagnosing intraductal lesions and serves as a guide for subsequent surgery in women with nipple discharge. In this article, we reported the outcomes of FDS combined with cytology testing for diagnosis of spontaneous nipple discharge. From 1997 to 2005, 1,048 women (1,093 breasts total) in the outpatient department underwent successful diagnostic FDS. Discharge was unilateral (86.8%), single ductal (93.4%), and serous (57.9%) or bloody (36.0%). Among 437 (40.0%) of the FDS-positive breasts, we revealed 49 (11.2%) breast carcinomas, 228 (52.2%) central papillomas, and 5 (1.1%) cases of atypical ductal hyperplasia. Ten patients with positive cytology testing received microdochectomy in spite of having a negative FDS, which revealed two additional ductal carcinomas in situ (DCIS), and four papillomas. About 489 breasts were negative for both FDS and cytology testing and were subjected to follow up. About 77 (15.7%) of the breasts underwent tissue diagnosis within a median follow-up time span of 19 months, and one DCIS was detected. The sensitivity of FDS for detection of malignant lesions was 94.2% and increased to 98.1% when combined with cytology testing. Nevertheless, it was less sensitive (p<0.01) if we used cytology testing only (58.3%), mammography (48.6%), high-frequency sonography (36.4%), or combination of mammography and sonography (56.8%) to detect these malignant lesions. These data confirmed the value of FDS combined with cytology testing as a diagnostic procedure in women with nipple discharge.

Referral patterns between the child health service, general practitioners, and secondary healthcare: A prospective descriptive study in the Netherlands

Background: In the Netherlands, preventive child health service (CHS) screening plays an important role in the early detection of congenital, developmental, physical, and mental disorders. Objective: To obtain insight into the referral patterns of children from CHS to general practitioners and from general practitioners to medical specialists. Methods: Prospective study over 6 months in a semi-urban area in the Netherlands. All correspondence from the participating doctors was sticker marked and, after each contact, a registration card was sent to a central secretariat. The referral stream between general practitioners and specialists or allied health professionals was extracted from a central database. The general practitioners and the participating paediatricians were asked to complete a questionnaire about the quality and necessity of the referral. Results: Out of an estimated 2600 examinations, 45 children were referred to their general practitioners for further examination. The problems of eight children were settled by the GP, 10 children were referred to allied health professionals, and 24 children were referred to specialists. The median time span of showing up at the GP's office was 6.5 days. Sixteen per cent showed up long after having been referred by the CHS. The parents of three children did not comply. Of the 397 referrals from GPs to medical specialists and allied health professionals, 8.5% were initiated by the CHS. Conclusion: The amount of referrals from the CHS to GPs and of referrals from GPs to medical specialists and allied health professionals initiated by the CHS is low in terms of absolute percentages. Most referrals by the CHS were considered useful.

Retransplantation with Stem Cells from Mismatched Related Donors after Graft Rejection in Pediatric Patients.

Graft failure is a rare but life-threatening complication after transplantation of hematopoietic stem cells. Treatment comprises immunoablative reconditioning regimens and a second stem cell donation from the same or from a different donor as soon as possible to minimize the time of pancytopenia and its sequelae.We report a cohort of 11 pediatric patients with leukemias (acute lymphatic n=4, acute or chronic myeloic/MDS n=4) and severe aplastic anemia (n=3) who experienced graft rejection after TBI, busulphan or melphalan based myeloablative transplantation from mismatched related donors (MMRD) (n=6) or after cord blood/matched unrelated donor (MUD) transplantation (n=5) between 2000 and 2006. In the latter the original donor was not available a second time. Thus, all patients were re-transplanted with CD34+ positive selected or CD3/CD19 depleted stem cells from a second, haploidentical parental donor (MACS method, Miltenyi Biotec). Median time span from diagnosis of graft rejection to second donation was 16 days. The reconditioning regimens consisted of total lymphoid irradiation or cyclophosphamide, thiotepa (5mg/kg), fludarabine (120 mg/m2) and ATG/OKT3. A median number of 25×106/kg of body weight stem cells with 60.000/kg residual T cells were infused. Mofetilmycophenolat was given as GvHD prophylaxis, if residual T cells exceeded 25 000/kg bw. Sustained engraftment was achieved in all patients (ANC>500/μl: 9 (11–32) days). No GvHD > grade II was observed. T cell recovery was delayed, however no lethal viral infection occurred. Severe organ toxicity was observed in 2 patients (BOOP, hemorrhagic cystits) and moderate mucositis in 11 patients. 8/11 patients are disease free (median follow up 1.5 (0.3–6.6) years; 1 year EFS=73%). Causes of death were: BOOP (n=1), infection (n=1); only one patient with refractory AML relapsed. Thus, transplantation of stem cells from haploidentical donors represents a realistic option to rescue patients with graft failure within a short time span and for whom a second donation of the original donor is not available. The use of a different donor may help to avoid a second rejection.

Improvised Cricothyrotomy Provides Reliable Airway Access in an Unembalmed Human Cadaver Model

Patients with injuries requiring surgical airway management occurring far from medical care might benefit from the availability of a simple, reliable, improvisational method of cricothyrotomy with materials available in a wilderness or prehospital setting. We evaluated an improvised cricothyrotomy device in an experimental, unembalmed human cadaver model. A high-flow intravenous spike and drip chamber was cut through the drip chamber and used as the sole apparatus for performing cricothyrotomy on unembalmed cadavers whose anterior neck surfaces and deep tissues were warmed to or near body temperature. Correct placement in the trachea and damage to the posterior wall of the trachea were assessed by either fiberoptic bronchoscopy or neck dissection. Video recordings were used to time each procedure. Each operator was responsible for both device insertion and bag valve mask attachment and ventilation, modeling as the sole care provider for the patient. One physician and 3 emergency medicine residents, all without previous, specific instruction, performed 10 procedures on 5 female and 5 male unembalmed cadavers weighing a mean of 65 kg (range 45-110 kg). All 10 attempts at placement of the intravenous tubing spike through the cricothyroid membrane were successful. On 2 attempts, the initial placement of the device was incorrect, but the error was immediately identified on attempt to ventilate the patient. Repositioning of the device resulted in appropriate cannulation of the trachea in both attempts. The median time span from manual identification of the cricothyroid membrane to percutaneous access and connection of the bag valve mask with successful ventilation was 27.3 seconds. Violation of the posterior tracheal wall was not seen on any of the 5 procedures in which fiberoptic visualization was available or in the 5 procedures evaluated by neck dissection. Cricothyrotomy is the quickest and most effective method for obtaining airway access when nonsurgical methods of securing the airway are contraindicated or fail. Although frequently described, no improvised airway devices of this type have been tested in a systematic manner. We tested the reliability and utility of cricothyrotomy with a high-flow intravenous spike and drip chamber. Our results suggest that the spike and drip chamber is a plausible means of temporarily establishing airway access in patients with acute airway obstruction in a wilderness or prehospital environment.

Feto-Amniotic Shunting - Experience of Six Centres

Foeto-amniotic shunting is an ultrasound-guided, therapeutic intervention for drainage of persistent intracavital fluid retention in severely affected foetuses with a high risk of mortality. In order to weigh up the comparatively high risk of intervention against the possible benefit, we evaluated the value of different indications, the complication rate and the time span of drains in situ. We made a survey of all level III ultrasound centres of German-speaking countries from 1993 to 2001. Six level III centres returned the questionnaire: forty-seven foeto-amniotic shunting procedures were performed in 30 foetuses [megacystis in 18 foetuses (three of these with urinary ascites), hydrothorax in eight foetuses, hydronephrosis in two foetuses, cystic adenomatoid malformation of the lung in one foetus, ovarian cyst in one foetus]. The median gestational age at time of shunting was 23.5 (range 16 - 33) weeks, at time of delivery 35 (range 23 - 41) weeks. The median time span of drains in situ was 19 (range 0 - 170) days. Altogether 18 of 30 foetuses (60 %) had a benefit of foeto-amniotic shunting. The best possible selection of pregnancies which might profit from foeto-amniotic shunting is required. The decisive criteria are the underlying defect as well as the severity and progression of the disorder.

Refluxanamnese von Patienten mit Adenokarzinom der Speiseröhre

Gastroesophageal reflux (GER) is the main risk factor for the development of adenocarcinoma of the esophagus (AC). The aim of our study was to evaluate symptoms of patients with AC to identify those patients with a high risk for this tumour. 117 consecutive patients with known AC were included. Prospectively all patients were interviewed with a standardised questionnaire comprising 120 items: social status, other diseases, risk factors, therapy of the GERD and, as a main part: current symptoms and those experienced at earlier times. 85 % of the patients had often or sometimes reflux symptoms. 46 % of the patients with reflux symptoms had such symptoms daily. The median time span for this symptom was 20 years with a range from 1 year to 50 years. In 21 % of the patients the reflux symptoms stopped (median) three years (range two months -- 30 years) before the diagnosis of the carcinoma. Only 55 % of all patients had one or more esophago-gastroscopy examinations before the diagnosis of AC. These patients showed significantly more often earlier tumour stages than those patients without an endoscopy before diagnosis. Heartburn was treated with medication in 78 % of the patients (67 % of all patients). No patient had previously undergone antireflux surgery. 15 % of the patients with adenocarcinoma of the esophagus show no, and in addition 25 % only discrete, heartburn; 1. an endoscopy due to heartburn was done in half of all cases, and 2. the medications do not fulfil the therapeutic standard; 3.patients with endoscopy had significantly more frequently an earlier tumour stage.

How to improve the search for an unrelated haematopoietic stem cell donor. Faster is better than more!

Many patients do not reach haematopoietic stem cell transplantation. Shortage of unrelated donors (UDs) is still seen as the main cause. However, with a worldwide UD pool containing more than 8 million donors, it is possible that other impediments are becoming more important. We analysed 549 UD searches for Dutch patients, performed between 1987 and 2000, in order to find the reasons for failure or success to reach transplantation. Between 1996 and 2000, 59% of the patients of Northwest European origin received a graft from an UD with a median time span of 4.4 months from the start of the search. In all, 11% of the patients lacked a compatible donor, while 30% became medically unfit for transplantation. This is in contrast to the patients of non-Northwest European origin for whom UD shortage is still the most important impediment; only 32% were transplanted while 50% lacked a compatible donor. We conclude that the shortage of donors is no longer the biggest constraint in unrelated stem cell transplantation for patients of Northwest European origin. It may be more effective to optimize the chance on transplantation by making the search process more efficient.

Time Course from First Symptom to the Treatment of Lung Cancer in the Eastern Black Sea Region of Turkey

Objectives: To determine the delay between the onset and the diagnosis and treatment of patients with lung cancer in two cancer centres in the Eastern Black Sea Region of Turkey. Subjects and Methods: The records of 226 patients (217 males, 9 females) were evaluated retrospectively for the dates noted for the onset of symptoms, first presentation to a physician, histopathological diagnosis and start of treatment. The median time intervals from the appearance of the first symptom to definitive diagnosis and treatment were calculated. Results: The patients presented to their physicians 30 (range 2–365) days after their complaints began. The time that elapsed between admission and histopathological diagnosis and between the diagnosis and initiation of therapy were 8 (range 1–210) and 17.5 days (range 0–206), respectively. The median time span from presentation to treatment was 30 days (range 1–253). There were no significant time interval differences between onset of symptoms and first presentation and the subsequent diagnostic and therapeutic processes for histopathology, stage of the tumour and treatment procedures (p > 0.05). Conclusion: Reasons for the delayed treatment of lung cancer patients were late presentation to the physician and the long time interval between tissue diagnosis and treatment. This delay was mostly associated with a large number of patients and delayed appointments for imaging procedures – the result of organisational problems within the health services of Turkey.

Retreatment or radiographic monitoring in endodontics

The aim of this clinical study was to assess 1032 endodontically treated roots in relation to: (i) the success rate of retreatment (612 roots)--only cases that had recall examinations of 6 months or longer were evaluated; (ii) the influence of various factors on the technical and clinical results of the retreatment; and (iii) the consequences of radiographic monitoring of 420 asymptomatic roots when the root filling was radiographically deficient (short, overextended and/or permeable root fillings). Technical assessment of the retreatment showed that the root was adequately sealed in 52.3% of cases, the root filling was improved in 33.8%, was identical with the initial treatment in 11.1% and was worse than the first treatment in 2.8% of the canals. Clinical assessment of the retreatment of symptomatic roots showed that 71.8% of the retreatments were judged successful, 18.9% showed some healing and 9.3% had failed. The initial size of the periapical lesion, the use of rubber dam, the root filling technique and the apical level of the root filling had a statistically significant influence on the result of the retreatment. Monitoring radiographically (median time span 6 years) led to maintenance of the status quo in 94.8% of cases, healing in 2.4% and failure in 2.8% of the canals. Retreatment is clearly indicated when periapical radiolucency, clinical signs and/or symptoms are present with relative success of up to 91%. When no or little radiographic evidence of periapical pathology was present, when clinical signs and symptoms were absent or when the root filling was radiographically deficient, radiographic monitoring led to complications in only a limited number of cases. clinical decision, endodontic retreatment, radiographic evaluation.

Intracerebral chemotherapy in the 9L rat brain tumor model.

We have used the 9L rat brain tumor model to search for effective chemotherapeutic approaches to the management of brain tumors. Several antineoplastic agents which have been proposed or are currently being used for human brain tumors, including 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), bleomycin, aziridinylbenzoquinone (AZQ), cis-Platinum, and acivicin, were administered intravenously (iv), intraperitoneally (ip), or intracerebrally (ic) to rats burdened with the intracranial 9L gliosarcoma. The results confirm that BCNU is the most effective systemic agent among the chemotherapeutic agents tested as indicated by its ability to significantly increase the median survival time (MST) and life span of the tumor-burdened animals. Bleomycin is an effective agent against the intracranial 9L tumor when administered ic. While neither systemic single iv dose AZQ (0.5-2.5 mg/kg) nor multiple ip treatments (0.5-1.0 mg/kg x 5, q 6 h) were effective in prolonging the survival, single ic dose AZQ (5-50 micrograms/rat) treatment significantly increased the MST of the treated animals (P < 0.05). Systemic AZQ treatments using higher doses produced a hematological toxicity, resulting in a decrease in MST of the treated animals. Cis-Platinum, either administered ip or ic, produced only a marginal effect on survival, although acute neurologic toxicity limited the dose of cis-Platinum that could be administered ic. Acivicin, either administered ip or ic, produced no effect on the survival of treated animals. Our results suggest that local treatment with certain antineoplastic agents may be an efficient therapy in the management of brain tumors.