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Biomedical subjects

H Mildenberger

Publications and source records attributed to H Mildenberger.

At least 19 recordsLinked to original sources
PubMed1995

Complete resection before development of drug resistance is essential for survival from advanced hepatoblastoma--a report from the German Cooperative Pediatric Liver Tumor Study HB-89.

Clinical data and tumor histology of 37 patients with advanced and/or metastatic hepatoblastoma (32 stage III and 5 stage IV) treated according to the protocol of the German Cooperative Pediatric Liver Tumor Study HB-89 from 1988 to 1992 were studied for prognostic factors. Twenty-three patients (73%) were free of tumor 9 months to 5 years (median, 36 months) after treatment, whereas 4 experienced progressive disease, 7 had local relapse, and 3 had recurrent metastases. None of 2 patients with primary lymph node involvement or 5 with primary metastases remained disease-free. Chemotherapy with ifosfamide, cisplatin, and adriamycin was effective in reduction of tumor to resectability in 33 (89%) patients. Drug resistance developed in 6 of 11 patients treated with four or more courses of chemotherapy as could be shown by monitoring of serum-alpha-fetoprotein (AFP) and serial investigations of tumor expansion with sonography and computed tomographic (CT) scan. Only 1 of these patients survived after a liver transplantation. Completeness of tumor resection at second- or third-look laparotomy was significantly related to disease-free survival (P < .0001). Patients with initial serum-AFP values < 100 ng/mL or > 1,000,000 ng/mL had a worse outcome than those with immediate levels (P = .044). The rate of decrease of serum-AFP during chemotherapy was significantly related to prognosis (P = .003). Growth pattern of tumor within the liver (ie, defined nodes versus diffusely disseminated) (P = .011) and vascular tumor invasion (P = .026) were valuable prognostic factors, whereas tumor volume, local infiltration of surrounding tissue, histological subtypes, and epithelial differentiation were not significantly related to the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Liver tumors in neonates and very young infants: diagnostic pitfalls and therapeutic problems.

We report on 26 infants under 3 months of age with various liver tumors, who were treated in our hospital since 1977 and/or registered in the German Cooperative Pediatric Liver Tumor Study HB-89. 17 of these had an infantile hemangioendothelioma (inf HE), 7 a hepatoblastoma (HB), one a mesenchymal hamartoma (mes H) and one a neuroblastoma stage IV-S (Nbl). Polyhydramnios occurred in 5 cases of inf HE, in one associated with hydrops fetalis. This led to a preterm delivery of 4 infants. 7 infants with a large inf HE suffered from high output congestive heart insufficiency, 2 additionally from a Kasabach-Merritt-syndrome. Serum alpha-fetoprotein was within normal range of age in all infants except in one HB patient. Neuron-specific enolase was clearly elevated in the Nbl patient and slightly above normal range in one inf HE and 3 HB patients. Other tumor markers and platelet counts were not indicative of diagnosis. Also imaging techniques as ultrasonography, CT and angiography were not always reliable in differentiating the tumors. In 2 cases the initial histological diagnosis of an HB had to be corrected for an inf HE. In 6 children the tumors were initially treated under a wrong assumption: 4 tumors as an HB instead of an inf HE, one as an inf HE instead of a Nbl IV-S and one as a focal nodular hyperplasia of the liver instead of an HB. 7 not resected inf HEs (Dehner type I) showed spontaneous regression after 6 months to 3 years. One inf HE type II relapsed twice after resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗
PubMed1994

Clinico-pathological criteria with prognostic relevance in hepatoblastoma.

We investigated clinical data and histological specimens of 46 patients with a hepatoblastoma (HB) for prognostic criteria. Disease-free survival (DFS) of 23 patients treated in the German Cooperative Study HB-89 (1988-1990) was 83%, in contrast to 40% in 10 children with other chemotherapy regimes (1977-1987) and 38% in 13 with only a tumour resection (P = 0.005). Tumour residence after resection (R category) correlated significantly with probability of DFS (P = 0.0001). This was also the case for pT status, according to the pTNM classification for liver carcinoma (P = 0.0007), involvement of one or both liver lobes (P = 0.004), multiplicity of tumour nodes (P = 0.001), vascular invasion (P = 0.0006) and expression of nucleolar organiser regions as an indicator for proliferation activity of tumour cells (P = 0.05). Patients' age and histopathological subtypes could only indicate outcome, while tumour size and serum alpha-fetoprotein values were not significantly related to prognosis. In multivariate analysis, pT status and R categories remained significant. These should be applied in all cooperative trials on HB.

Child↗
PubMed1994

Is laparatomy the first step in treatment of childhood liver tumors?--The experience from the German Cooperative Pediatric Liver Tumor Study HB-89.

In the cooperative study on childhood liver tumors (HB-89) of the German Society for Pediatric Oncology and Hematology an initial laparotomy was recommended for all children with a primary liver tumor. Now a more differentiated surgical strategy has been worked out on the basis of study data. Patient's age, alpha-fetoprotein or other tumor markers, imaging techniques and histological investigations were predictive for differential diagnosis in most, but not all cases. Surgical complications occurred infrequently, there was no perioperative mortality. Results of therapy were satisfactory in hepatoblastoma, but poor in hepatocellular carcinoma, since chemotherapy and radiation were not effective on this tumor. In conclusion, primary chemotherapy without histological confirmation is justified, if in children between six months and three years of age with a high serum-alpha-fetoprotein a hepatoblastoma is certain, and the tumor involves both lobes of the liver. All other patients should have an initial laparotomy for resection of small or biopsy of large tumors. In case of hepatocellular carcinoma a primary resection should be attempted on principle.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[HB89: the liver tumor study of the Society for Paediatric Oncology. An interim report].

After completion of a pilot phase in 1988, the liver tumour study HB89 of the German Society of Paediatric Oncology started on January 1st, 1989. Up to the end of 1990, 54 children with a primary tumour of the liver where enrolled into the study. Thirty-six of them suffered from hepatoblastoma, 8 from hepatocarcinoma. Thirteen of the hepatoblastomas could be resected primarily, 17 were removed following preoperative chemotherapy. One patient with a stage III hepatoblastoma underwent successfully liver transplantation. At the end of 1990, 28 patients were in first remission (78%), two were still under chemotherapy, and six had died after tumour progression or relapse. Out of eight patients with hepatocarcinoma, only two with a primarily resected tumour are still in first remission. Chemotherapy with ifosfamide, cis-platinum, and adriamycin (IPA) or with continuous infusion of cis-platinum and adriamycin (PAcont) was effective in hepatoblastomas but not in hepatocarcinomas. Because of the problems of preoperative differential diagnosis and judgement of resectability, a primary laparotomy with an open tumour biopsy is necessary. Following the HB89 study protocol with its strategy of graded surgical treatment, the rate of resection was high, the perioperative morbidity low, and no death due to surgery was observed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Urethral reconstruction using an autologous bladder mucosal graft.

Since 1988 twelve children underwent urethral reconstruction by using an autologous bladder mucosal graft. In 10 of these previous surgery for hypospadias or other penile anomalies had failed. Bladder mucosal graft was used in 2 cases for primary urethral reconstruction. Our results in using this method, mostly in hypospadias cripples, are satisfying, so that we are encouraged to use the autologous bladder mucosal graft for primary urethral reconstruction in selected cases with severe forms of hypospadias as well.

Adolescent↗
PubMed1991

Occlusion of liver veins (Budd-Chiari syndrome) in childhood: a case report.

The Budd-Chiari syndrome is a rare cause of portal hypertension during childhood. We report on a 2-year-old boy suffering from liver congestion and ascites. No cause for the occlusion of the liver veins was found. There was an almost complete occlusion of the subdiaphragmatic vena cava due to compression by a hypertrophic lobus caudatus. Normal venous pressure could be demonstrated below this subtotal occlusion while numerous venous collaterals into the areas of the venae azygos and hemiazygos were encountered. A mesocaval shunt operation, therefore, seemed to be appropriate. There was, however, no decrease in production of ascites postoperatively. Repeat cavography now showed an elevation of venous pressure caused by the additional inflow of portal blood which could not, as expected, be compensated by caval collaterals. Therefore, a mesoatrial shunt was performed eight days after the first operation. However, even this additional shunt did not decrease the enormous production of ascites, and the child finally died. Hemodynamic and lymphodynamic pathways of the Budd-Chiari syndrome are discussed. Possibly a mesoatrial shunt in the first place, followed by a mesocaval shunt, would have been the better operative strategy.

Ascites↗
PubMed1989

Monoclonal antibody T-199 directed against human medulloblastoma: characterization of a new antigenic system expressed on neuroectodermal tumors and natural killer cells.

A monoclonal antibody (mAb) (T-199) of IgG1 isotype was raised against medulloblastoma by immunizations of mice with the medulloblastoma cell line TE-671. Studies of the specificity of mAb T-199 on cell lines as well as fresh frozen sections of normal and malignant tissues revealed the antigen in high amounts on the cell surface of neuroectodermally derived tumors such as medulloblastoma, neuroblastoma, retinoblastoma, and astrocytoma. Some melanomas and a subgroup of rhabdomyosarcomas also expressed the antigen. In contrast, mesenchymal tumors, osteosarcomas, and Ewing's sarcomas did not bear the T-199 antigen. Reactivity of T-199 with normal tissues has not been found with few exceptions; in certain areas of the brain, especially in the cerebellum and part of the hypothalamus, in the adrenal glands, and in the pancreatic islet cells small amounts of antigen were detectable. Natural killer cells could also be demonstrated to express the T-199 antigen similar to the NKH-1 antigen. However, despite some striking similarities, the antigens or antigen epitopes recognized by mAbs T-199 and NKH-1 are not identical. Therefore, mAb T-199 seems to detect a unique differentiation antigen on neuroectodermal tumors, coexpressed in low amounts on normal neuroectodermally derived cells and natural killer cells. The pattern of reactivity and the biochemical properties of the T-199 antigen are different from other cell surface markers for neuroectodermal cells coexpressed on natural killer cells or T-cells (HNK-1, NKH-1, or Thy-1). Biochemical analysis of the T-199 antigen showed that it is a heat-labile protein.

Antibodies, Monoclonal↗
PubMed1989

Infants with posterior urethral valves: a retrospective study and consequences for therapy.

This is a report on the follow-up data of 18 patients with posterior urethral valves diagnosed during the first year of life. One infant died of progressive renal failure; a slight elevation of serum creatinine levels in three children aged 4-6 years indicated a doubtful prognosis. On initial examination, ten patients showed severe unilateral or bilateral reflux. Seven of 14 refluxing units remained non-functioning and had to be removed. Following transurethral fulguration of the valves, five infants developed unilateral or bilateral reflux which was not evident on initial preoperative voiding cystograms. In contrast to those in other series, none of these refluxes ceased spontaneously. Ureteral reimplantations were done on 11 ureters of eight patients, but regression of ureteral dilatation postoperatively remained unsatisfactory in six instances, none of whom had a true mechanical obstruction. We conclude that many of these megaloureters encountered in infants with posterior urethral valves are concomitant with profound and often irreversible damage of the ureter wall. Surgery of such ureters, therefore, should be avoided whenever feasible.

Follow-Up Studies↗
PubMed1989

[The development of the early genital anlage and its significance for the development of the large intestine--studies of rat embryos].

The morphology of infraumbilical malformations suggests that the development of the genital anlage is of great importance for the embryology of the cloaca. In rat embryos the development of the genital anlage is documented using scanning electron microscopy. This documentation suggests that the genital anlage develops in three phases. Of these, the development of the unpaired glandular hillock seems to be especially important. The genital anlage affects the development of the cloaca in two ways: firstly its ventral growth causes a ventral shifting of the greater part of the cloaca into the region of the genitalia and secondly the cloaca gains its definite position through the development and growth of the glandular hillock.

Animals↗
PubMed1989

[Hepatoblastoma: a catamnestic study and proposal of a therapy concept].

Since 1977, 28 infants and children with hepatoblastomas were seen in the Department of Paediatric Surgery, Hanover Medical School. Five tumours could only be biopsied. One 11-months-old infant had a successful liver transplantation done at the Dept. of Transplantation Surgery (Professor R. Pichlmayr). Following a biopsy for unresectable tumour, chemotherapy was instituted in 5 cases: three of these could be resected in a second look operation 10 to 26 weeks later. Altogether, 22 tumours (= 81%) were resected: 14 had an extended resection (trisegmentectomy), and 8 had a lobectomy. Operative mortality was 14%. Out of 27 patients which were operated upon (resection or biopsy) longer than one year ago, 11 are alive and free from disease (= 40%). Early metastatic disease was diagnosed 3 weeks to 5 months postoperatively in 5 cases: only one of these children survived, following an intensive course of chemotherapy. In another two patients lung metastases were found 14 resp. 20 months after operation: both of these are alive and free from disease following chemotherapy and thoracotomy. One patient died of brain metastases 3 years postoperatively. Results of therapy are correlated to primary findings, type of operation, chemotherapy and histological subtype of the tumour. In comparison with published data a possible advantage of more aggressive operative strategies is discussed, and the benefit of a preoperative chemotherapy is evaluated. As a result of these considerations a treatment protocol for hepatoblastomas is proposed, designed as a national multicentre prospective study conducted by the German Society of Paediatric Oncology (GPO).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Embryology of bladder exstrophy.

A hypothesis in respect to the teratogenesis of bladder exstrophy and its variants is offered. The central feature of this hypothesis is the abnormal persistence of the caudal position of the insertion of the body stalk on the embryo. As a consequence of this, the normal advance and interposition of mesenchymal tissue to the midline becomes impossible. The cloaca cannot be translocated backwards into the body cavity, and the cranial end of the cloacal membrane remains in contact with the inferior aspect of the low-set body stalk. This, in contrast to the previously proposed abnormal rostral extension of the cloacal membrane, causes a wedge-effect resulting in the lateralization of the abdominal wall structures and also in the prevention of the midline fusion of the genital hillocks (labioscrotal or genital folds). A cloacal membrane normally is an unstable structure lacking mesoderm, and it retains these characteristics in the superficial and infraumbilical position to be described. It has a strong tendency to disintegrate. It may rupture at variable times and to a variable extent. The consequence of such an embryonic event is either a typical bladder exstrophy or one of the variants of the exstrophy malformation. Three different variants are presented that the proposed embryologic hypothesis can readily explain.

Animals↗
PubMed1988

[Hypospadias in the female].

Female hypospadias is a rare, but well defined anomaly of the lower urogenital system. From an embryologic point of view it represents an arrest during a late stage of sinus urogenitalis development. It is not to be confused with minor variants of the external urethral meatus of a doubtful clinical relevance. The main symptom is a severe subvesical obstruction, and usually it presents early in infancy. A case is presented, in which on the basis of the incorrect diagnosis of "occult neurogenic bladder outlet obstruction" a supravesical diversion (ileal conduit) was done. Undiversion was successfully carried out at an age of 7 years.

Child↗
PubMed1988

[Tracheal agenesis: which surgical measures are sensible?].

Tracheal agenesis is a rare congenital malformation. Up to now no surgical concept exists for a definitive correction. In this paper we describe our experiences with an own case and discuss the purpose and justification of temporary surgical measures.

Asphyxia Neonatorum↗
PubMed1988

[Accomplishments of tumor surgery in neuroblastoma in childhood].

Survival rates in patients with neuroblastoma did not significantly improve during the last two decades. This is particularly true for stage IV tumors. This stage seems to be a tumor fundamentally different from the more localized stages in its biological behavior, and it is not known, whether stage IV tumors originate from a localized stage by metastatic spread. Intensive investigations regarding new therapeutic approaches on an immunological basis or by stimulation of tumor maturation have been unsuccessful by now. Surgery in neuroblastoma has to be adapted to the particular stage to be treated. Certainly, surgery has to be incorporated into a therapeutic strategy which includes the whole spectrum of modern anticancer therapy. Such a therapeutic strategy will be provided by multicenter cooperative studies, such as the neuroblastoma study designed by the German Association of Paediatric Oncology (GPO). A treatment of neuroblastoma without incorporation in a multicenter cooperative study should not be accepted as modern standard.

Child↗
PubMed1985

The advantages of preoperative therapy in Wilms' tumour. A summarised report on clinical trials conducted by the International Society of Paediatric Oncology (SIOP).

During 1971-1980, three consecutive clinical studies on nephroblastoma were conducted by the International Society of Paediatric Oncology (SIOP). Besides several questions on different postoperative treatment modalities, the emphasis of these trials was to determine the role of preoperative therapy. In SIOP-1 (1971-1974) we compared preoperative radiotherapy to immediate surgery. There is no difference in survival or recurrence-free survival between both groups. Tumour ruptures, however, did occur significantly less in the pretreated group, and the recurrence-free survival is clearly lower in patients with intraoperative tumour rupture. These results were confirmed by SIOP-2, a non-randomised study conducted between 1974 and 1976. The question tackled by SIOP-5 (1977-1980) was whether preoperative chemotherapy could be a substitute for preoperative radiotherapy. The two preoperative therapies produced equally satisfactory results in terms of recurrence-free survival and 4-year survival rates, and the reduction in the number of operative ruptures. In addition, it was shown that with preoperative chemotherapy about 45% of an unselected population of patients with Wilms' tumour can be treated and cured without any irradiation and its well-known sequelae. The actual need for radiotherapy in stage II tumours with negative lymph node involvement (about 30% of the patients after pretreatment) is under investigation in SIOP-6. Cytohistological grading is equally possible after chemotherapy, and also without pretreatment. If antitumour treatment is begun before histopathological diagnosis, then the risk of overtreating patients with benign conditions, or of administering an inappropriate treatment to patients with malignant tumours of other types, is about 6%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

[Stress tolerance of the patient in pediatric surgery].

In pediatric surgery pain and suffering are not those dominant problems as in adult surgery. So even an extended operative procedure can be performed in a child without hesitation, if it seems to be useful. Much more than in adult medicine, the pediatric surgeon has to consider the consequences of his treatment on the whole family, esp. on the patient's mother. There is a lack of experience concerning toleration of a pregnancy by a mother who knows already about a treatable malformation of the fetus. Two cases are presented: omphalocele and gastroschisis.

Child, Preschool↗