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Biomedical subjects

H Mildenberger

Publications and source records attributed to H Mildenberger.

At least 19 recordsLinked to original sources

Retroperitoneal lymphangiomyoma in an infant.

Lymphangiomyomatosis (LAM) is a benign tumor-like lesion of lymphatic vessels with unknown etiology. 80 cases of LAM are presently described. So far, it appears that only women in their reproductive years seem to be affected. Here, we describe the first LAM in an 11-months-old infant with a presumably local form of LAM. This leads us to consider the possibility that this tumor-like lesion may originate from a hamartomateous malformation. The diagnosis is based on pre-operative sonography and CT, as well as on histological and immunohistochemical examination of the tumor.

Female

One-stage reconstruction of bladder exstrophy.

From 1984 to 1990 a primary one-stage reconstruction of bladder exstrophy was performed at our hospital on 15 consecutive infants. Reconstruction included Cohen's ureteral reimplantation, bladder neck reconstruction according to Young-Dees, bladder closure, symphyseal bone approximation, abdominal wall closure, and repair of epispadias in females. Postoperatively, all patients were immobilized by overhead extension. Iliac osteotomy was done in 9 children, but was abandoned in recent years for infants less than one month old Follow-up examinations included an interview with the parents, clinical examinations, blood and urine analyses, uroflowmetry, and ultrasound scan of the abdomen. Nuclear renal scan, i.v. pyelography, and cystography were carried out as indicated. At the time of last evaluation the children were between 3 and 9 years of age. The cosmetic results were satisfactory in all cases. Eight of 15 children were dry day and night with micturition intervals more than 3 hours during day time (complete continence). Five children were dry during day time with micturition intervals up to 3 hours, but occasionally wet their beds (partial continence). Two children were incontinent. Eleven of 15 children had a bladder capacity of more than 100 ml. Renal function was normal in all patients. Two children showed a mild VUR, and no other abnormalities of the upper urinary tracts were found. Iliac osteotomy did not influence the functional or cosmetic results, but in two patients asymmetry of pelvic bones with consecutive lumbar scoliosis was found. Comparing these results with reports on staged reconstructive procedures, we conclude that by primary complete one-stage reconstruction a well acceptable success rate is achieved, and that by this method possibly some advantages are offered to patients with bladder exstrophy.

Bladder Exstrophy

[Surgical strategy in pediatric liver malignancies].

The therapeutic results of two groups of children with liver tumours were compared: group 1 [29 hepatoblastomas (HB) and five liver carcinomas (HCC)] were operated before 1987, and group 2 (88 HB and 16 HCC) were treated according to the studies HB 89 and HB 94 of the GPOH from 1988 onwards. Resection rates for HB were 81% (group 1) and 93% (group 2), with tumour-free survival rates of 38% and 77%, respectively: anatomic liver resections were more often radical than atypical tumour resections. Resections of lung metastases and liver transplantations increased tumour-free survival. In HCC therapeutic results were equally poor (25% cure). Thus in HB combined chemotherapy and surgery is highly effective, but HCCs are cured only by radical resections.

Carcinoma, Hepatocellular

[Oncologic surgery of malignancies in childhood. Effect of adjuvant/neoadjuvant methods].

Pre- and/or postoperative chemotherapy is highly effective in the treatment of pediatric malignancies and has modified surgical strategies significantly. (1) In childhood abdominal Non-Hodgkin-Lymphomas early chemotherapy has a definite priority over extended excisions. (2) In hepatoblastomas, radical excision is essential for effecting a cure. However, in the case of an advanced tumor, it is wise to start treatment with chemotherapy and then to perform surgery. (3) Pre-operative chemotherapy in Wilms' tumors effects a "down staging", which allows therapy reduction and omission of postoperative radiotherapy in the majority of cases.

Chemotherapy, Adjuvant

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

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

Experience with repair of 120 hypospadias using Mathieu's procedure.

Between 1985 and 1993 120 boys with distal hypospadias (from distal penile shaft to glandular position) were treated using Mathieu's procedure at the department of pediatric surgery, Hannover Medical School, Germany. The outcome of these cases has been analysed. Fistula-rate was 12.5%. Results are compared with published reports, recent developments and changes in treatment are discussed.

Adolescent

[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

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

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

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

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

[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

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

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

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