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Biomedical subjects

H Mildenberger

Publications and source records attributed to H Mildenberger.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Surgical therapy of hepatoblastoma in childhood].

Hepatoblastoma is a rare but highly malignant liver tumour, predominantly occurring during early childhood. Clinical data of 71 children treated from 1988 to 1993 according to the protocol of the multicentre liver tumour study (HB89) of the German Society for Paediatric Oncology and Haematology were evaluated to assess the effects of surgical therapy in these patients. The protocol prescribed an initial laparotomy for all children with a liver tumour, except for infants with distant metastases and a high serum-alpha-fetoprotein; for small hepatoblastomas confined to one liver lobe primary resection by a lobectomy; and for those extending into both lobes and metastasizing tumours tumour reductive chemotherapy including ifosfamide, cisplatin and adriamycin (IPA), preparatory to resection at second-look surgery. All patients received adjuvant IPA chemotherapy after tumour resection. In 20 of the 71 cases, the hepatoblastomas were completely resected at initial laparotomy (stage I), while in 6 cases microscopic residues were left (stage II). In 38 of 45 children with extended hepatoblastomas (stage III, 38 patients) or distant metastases (stage IV, 7 patients) the tumour was resected during later surgery, and 1 patient received a liver transplant. Thus, the overall resection rate was 92% (65 of 71 hepatoblastomas). After a median follow-up of 3.8 years (range 1.0-5.9 years), 53 (75%) of the patients were tumor-free and 18 (25%) had died. Recurrence-free survival was 100% for stage I, 50% for stage II, 71% for stage III and 29% for stage IV patients (P = 0.0009).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
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

The role of initial laparotomy and second-look surgery in the treatment of abdominal B-cell non-Hodgkin's lymphoma of childhood. A report of the BFM Group.

The aim of this study was to determine the role of surgery in the treatment of abdominal B-cell non-Hodgkin's lymphomas (B-NHL) in children. We analyzed the effect of surgical variables of initial laparotomy and second-look surgery on event-free survival (EFS) of 177 patients with abdominal B-NHL enrolled into the three consecutive multicenter trials NHL-BFM 81, NHL-BFM 83, and NHL-BFM 86. The therapy regimen was comparable in all 3 trials as well as the overall outcome of the patients. Patients with stage II and complete resection received 3 courses of therapy (4 in trial NHL-BFM 81), patients with stage II not resected, stage III, and stage IV received 6 courses of therapy (8 in trial NHL-BFM 81). An initial laparotomy was performed in 161 patients, in 59 of them as an urgent procedure. Complete resection of the abdominal primary was performed in 43 patients, 40 of them had a localized bowel tumor. The probability of EFS (pEFS) at 5 years is 95%, 69%, 62%, and 67% for patients with complete resection, subtotal resection (n = 36), partial resection (n = 21), or biopsy only (n = 61), respectively. Complete resection was achieved in 30 out of 40 patients with stage II, but only in 12 of 113 and 1 of 24 patients with stage III and IV, respectively. pEFS at 5 years according to stage and completeness of resection is as follows: stage II complete resected 97%; stage II not complete resected 100%; stage III/IV complete resected 92%; stage III/IV not complete resected 63%.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Neoplasms↗
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↗
PubMed1993

Production of interleukin-1 beta and interleukin-6 in hepatoblastoma.

Thrombocytosis and fever are frequent symptoms in children with hepatoblastoma. Interleukin-6 (IL-6) has been shown to mediate thrombocytosis and an acute-phase reaction including fever. We therefore investigated samples from 14 untreated patients with hepatoblastoma for this cytokine and in addition for interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), all of which are known to induce IL-6 production. High serum levels of IL-6 were only found in 3/14 patients; the other cytokines were not detectable. In contrast, 12/14 tumors produced substantial amounts of IL-6 in primary cell culture, while IL-1 beta was found in 3/14 supernatants; IL-1 alpha and TNF-alpha were always negative. Immunoenzymatic staining of fresh tumors revealed that IL-6 is not produced by the tumor cells, but rather by surrounding fibroblasts and endothelial cells. In tumor cells only IL-1 beta, but neither IL-1 alpha, TNF-alpha nor IL-6, could be detected. In co-culture experiments with fibroblasts and endothelial cells, addition of hepatoblastoma cells enhanced IL-6 production. Including an IL-1 receptor antagonist abolished this effect incompletely. Our results suggest that tumor cells in hepatoblastoma induce IL-6 production in surrounding fibroblasts and endothelial cells by virtue of their endogenous secretion of IL-1 beta and supposedly some other, as yet unidentified, mediator.

Carcinoma, Hepatocellular↗
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↗