Biomedical subjects

J C Hoehner

Publications and source records attributed to J C Hoehner.

16 recordsLinked to original sources

PubMed1998

Long-term morbidity in total colonic aganglionosis.

BACKGROUND/PURPOSE: No surgical treatment for total colonic aganglionosis (TCA) clearly has been proven superior. To identify clinical criteria associated with long-term functional outcome, a 28-year retrospective institutional review of this entity from 1969 through 1996 inclusive was undertaken. METHODS: Total colonic aganglionosis (TCA), defined here as aganglionosis extending from the anus to at least the ileocecal valve but no further than 50 cm proximal to the ileocecal valve, was identified in 29 infants and children. Appropriate leveling ileostomy was performed in 28 of 29 patients, and definitive surgical reconstruction was performed in 26 of 29. Three groups were identified based on the definitive surgical repair performed: group 1, construction lacking or incorporating a short ganglionic-aganglionic common channel (modified Soave or modified Duhamel, n = 8); group II, construction of an extended common channel (Martin-Duhamel, Martin-Soave; n = 6); and group III, all others including an intermediate-length common channel (n = 13). RESULTS: Functional outcome at extended follow-up (mean, 6.6 +/- 5.6 years; range, 0.7 to 23) was determined based on survival, long-term ostomy requirements, growth, major complications, continence, and enterocolitis and bowel movement frequency. Although long-term functional outcome was deemed satisfactory in six of seven patients in group I, function was satisfactory in none of six group II patients. Group III results were intermediate (satisfactory in 6 of 13). CONCLUSIONS: Acceptable long-term outcome was most frequent in TCA patients whose definitive repair did not incorporate an extended ganglionic-aganglionic common channel. The use of extensive lengths of aganglionic bowel to maximize fluid absorption is frequently met with substantial morbidity.

Analysis of Variance↗

PubMed1998

Management of gastroschisis with concomitant jejuno-ileal atresia.

BACKGROUND: The incidence of jejuno-ileal atresia in neonates concomitantly found to possess gastroschisis has been reported to be 5% to 25%. Initial treatment for this condition has not been well established. METHODS: Thirteen newborns with gastroschisis and coexisting jejuno-ileal atresia, were identified and treated at our institution over the past 16 years (1978 through 1996). Patient characteristics at presentation, surgical therapy, and complications at extended follow-up were reviewed. RESULTS: All neonates were preterm (mean gestational age, 35.2 +/- 2.0 weeks) and of low birth weight (2.1 +/- 0.4 kg). Atresia types II, IIIa, IIIb, and IV were identified at the initial surgical procedure in one, eight, one, and three patients respectively; however, one synchronous small bowel atresia went unrecognized. A primary anastomosis was fashioned in 8 of 13 newborns, the creation of which did not influence length of hospitalization, length of total parenteral nutrition (TPN) requirement, complication rate, or survival; however, reoperation was required in two of eight patients to mediate anastomotic complications. Atresia associated with intestinal gangrene or perforation was treated by primary anastomosis in three of six patients and the remaining three by enterostomy. Primary abdominal wall closure was possible in 10 of 13 patients; a Silon pouch was required in three. All nine survivors (69%) displayed protracted small bowel dysfunction requiring TPN (mean TPN duration of 3.6 +/- 3.0 months; range, 1 to 11). Mortality in four patients was a consequence of severe prematurity, Silon pouch wound sepsis, or TPN-induced cirrhosis. CONCLUSIONS: When technically feasible, restoration of intestinal continuity by primary anastomosis is a reasonable treatment option in patients with coexisting gastroschisis and jejuno-ileal atresia. Favorable outcome is as much a function of supportive care and parenteral nutrition as the type of surgical repair performed for either the intestinal or the abdominal wall defect.

Abdominal Muscles↗

PubMed1998

Developmental gene expression of sympathetic nervous system tumors reflects their histogenesis.

Comparisons of the developing human sympathetic nervous system (SNS) to tumors presumed to derive from these cells may suggest tumor progenitors and predict tumor biologic behavior. Classic neuroblastoma (NB) and its more highly differentiated stroma-rich subtypes, extra-adrenal sympathetic paraganglioma, and pheochromocytoma were examined for the presence of the developmentally characterized gene products NSE, S-100, CD44, Bcl-2, HNK-1, PNMT, TrkA, IGF2, and tyrosine hydroxylase. The marker gene expression profiles of these tumors were compared with those similarly determined for a number of normal prenatal and postnatal human SNS cell types. Sympathetic paraganglioma, pheochromocytoma, and stroma-rich NB display marker expression profiles mimicking those of childhood sympathetic paraganglia, adrenal chromaffin cells, and sympathetic neurons, respectively. A selection of differentiating, extra-adrenal NB tumors with prognostically favorable features possess marker gene expression profiles paralleling that observed for fetal extra-adrenal sympathetic paraganglia/small intensely fluorescent cells. In contrast, undifferentiated, clinically aggressive NB tumors manifest characteristics mirroring that of embryonic/early fetal sympathetic neuroblasts of sympathetic ganglia and of the adrenal gland. These findings suggest that clinical features, such as primary tumor location and age at diagnosis, provide prognostic information for NB patients by virtue of the existence and biology of the presumed tumor progenitor cell type.

Adrenal Gland Neoplasms↗

PubMed1997

Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma.

Several unique features of neuroblastoma (NB), including the capacity for spontaneous regression and maturation to benign pathology, suggest that genes that regulate cellular proliferation, survival and differentiation may be involved in directing clinical tumour aggressiveness. The in situ expression of Bcl-2, Rb, p21, p53 and Bax proteins, as well as the proliferation marker proliferating cell nuclear antigen (PCNA) were examined immunocytochemically in a selection of 38 stage- and outcome-identified NB tumours. Apoptotic cells were identified morphologically and by a DNA fragmentation labelling technique (TUNEL). Although the tumour cell density of Bcl-2, p53, Bax, PCNA and TUNEL positivity correlated with patient survival, a spatially organized expression pattern was further recognized in stroma-poor differentiating tumours. Immature tumour cells adjacent to thin fibrovascular stroma are proliferating, as evidenced by PCNA positivity, and often express Bcl-2. At increasing distance from this fibrovascular stroma, intermediately differentiated tumour cells express Rb, while with more advanced differentiation, proliferation ceases and Bcl-2 immunoreactivity is lost. The most differentiated tumour cells, which often express p53, and occasionally p21 and Bax, lie adjacent to TUNEL-positive, morphologically apoptotic cells. This spatial organization in favourable outcome NB tumours suggests that physiological regulation of differentiation and apoptosis may be involved in tumour regression.

Apoptosis↗

PubMed1997

In vivo spontaneous neuronal to neuroendocrine lineage conversion in a subset of neuroblastomas.

Neuroblastoma is an embryonal tumor derived from the sympathetic nervous system. Although all neuroblastomas have a neuronal character, a subset of tumors also show evidence of extra-adrenal neuroendocrine differentiation in discrete cell layers. A characterization of the cells of the developing human sympathetic nervous system was performed, identifying growth-associated protein-43, neuropeptide tyrosine, and Bcl-2 as marker genes for sympathetic neurons. Whereas all neuroblastomas express growth-associated protein-43, neuropeptide tyrosine, and Bcl-2, tumors with differentiating cells with neuroendocrine features expressed these genes only in the morphologically immature, proliferating cells. Thus, with neuroendocrine tumor cell differentiation, neuronal marker gene expression vanished and proliferation ceased and was succeeded by expression of chromogranin A/B and insulin-like growth factor-2, markers of neuroendocrine chromaffin differentiation. These tumors appear to provide examples of spontaneous lineage conversion from a neuronal to a neuroendocrine phenotype.

Cell Differentiation↗

PubMed1996

Neurotrophin receptors, tumor progression and tumor maturation.

The nerve growth factor receptor TrkA was initially isolated as a transforming oncogene, trk, in which most of the extracellular receptor part is replaced by the coding sequence for a tropomyosin-encoding gene. The impact that the identification of the first neurotrophin receptor has made on the entire field of developmental neurobiology cannot be overstated. Following a brief introduction to the biology of neurotrophins and their receptors, this review will focus on oncogenic Trk in human malignant disorders, discuss putative tumorigenic involvement of Trk family members in the childhood malignancy neuroblastoma, and point out potential neurotrophin-based treatment modalities for this and other neuroendocrine tumors.

Apoptosis↗

PubMed1996

Alterations in neurotrophin and neurotrophin-receptor localization in Hirschsprung's disease.

Interactions of the trk family of tyrosine kinase receptors with neurotrophins promote growth and differentiation of nervous-system cells during development. Disturbances in neurotrophic signalling could be involved in functional or aganglionic conditions of the intestine such as Hirschsprung's disease (HD). Intestinal resection specimens from 20 children with HD and from 10 normal age-matched controls were evaluated immunocytochemically for the presence of TrkA, TrkB, and TrkC protein, and the neurotrophin ligands brain-derived neurotrophic factor [BDNF] and neurotrophin-3 (NT-3). All three neurotrophin receptors are localized with cellular specificity to the enteric nervous system of normal and proximal ganglionic HD intestine; however, none was detected in the hypertrophic nerve fibers of aganglionic HD segments. Aganglionic HD intestine lacked intense and specific TrkC and BDNF enteric ganglionic immunoreactivity. NT-3, localized to enteric plexuses and basal lamina of ganglionic intestine, was not detected in ganglion cells located at the "transitional zone" of HD intestine. These data suggest that neurotrophic influences may be involved in enteric nervous-system cellular survival and differentiation in functional intestinal disorders such as HD.

Brain-Derived Neurotrophic Factor↗

PubMed1996

Localization of neurotrophins and their high-affinity receptors during human enteric nervous system development.

BACKGROUND & AIMS: Interactions of neurotrophins with the appropriate trk receptors result in growth and maturational alterations in nervous system cells during development. The aim of this study was to examine whether similar interactions could be involved in human enteric nervous system (ENS) survival or differentiation as well. METHODS: Immunocytochemical detection of TrkA, TrkB, and TrkC, as well as the ligands neurotrophin 3 (NT-3) and brain-derived neurotrophic factor (BDNF), was accomplished on normal human fetal and postnatal intestine. RESULTS: Neither neurotrophins nor their receptors were identified in immature postmigrational ENS progenitors at 7 weeks' fetal developmental age; however, TrkC and TrkA were specifically localized to developing ENS cells after 19 developmental weeks. From infancy through adulthood, TrkA and TrkB immunoreactivities were localized to both enteric ganglion cells and glia, whereas TrkC was localized exclusively to enteric ganglion cells. In postnatal intestine, BDNF immunoreactivity was primarily localized to enteric ganglion cells, with NT-3 localized to enteric plexuses, intermuscular basal lamina, and along or between circular and longitudinal smooth muscle cells. CONCLUSIONS: These data indicate that neurotrophic influences may be involved in ENS development and survival, with potential importance in functional differentiation disorders of the intestinal ENS.

Adult↗

PubMed1996

A developmental model of neuroblastoma: differentiating stroma-poor tumors' progress along an extra-adrenal chromaffin lineage.

The prognosis of children with neuroblastoma (NB) is dependent upon the patient's age at diagnosis, the location of the primary tumor, and histologic tumor cell differentiation. These characteristics, as well as the presumption that NB results from clonal expansion of primitive cells involved in sympathetic nervous system (SNS) development, predict that a model of tumorigenesis based upon normal fetal SNS histogenesis might indicate tumor progenitor status and define biologic and clinical behavior. Immunohistochemistry and in situ hybridization were used to examine a panel of marker gene products predicted or shown to be expressed during SNS development in the normal human fetal SNS from 8 to 24 weeks' gestational age. A similar analysis was performed in a selection of clinical NB tumors, and the results were compared. In a subset of differentiating, often extra-adrenal NB tumors in patients who frequently had a favorable outcome; advancing morphologic tumor cell differentiation spatially paralleled an advancing fetal extra-adrenal chromaffin marker gene expression phenotype (ie, increasing TrkA, TrkC, TH, IGF-2, and neuron-specific enolase expression but a lack of phenylethanolamine N-methyltransferase expression). In these tumors, expression of gene products associated with normal fetal sympathetic ganglionic differentiation (ie, Bcl-2, HNK-1, and neuropeptide Y) was lost with morphologic tumor cell differentiation. In contrast, undifferentiated tumors, the majority of which were high stage, adrenal in origin, and prognostically unfavorable, displayed marker expression characteristics mirroring that of an early fetal ganglionic lineage. Thus, we show that morphologic differentiation in stroma-poor NB tumors, long held as an important prognostic feature in tumor grading systems, often corresponds to an extra-adrenal chromaffin rather than a ganglion cell or adrenal medullary chromaffin phenotype. Understanding the biology of extra-adrenal chromaffin tissues may provide an explanation for the clinically less aggressive nature of differentiating NB tumors and suggest potential mechanisms for spontaneous regression and/or treatment response.

Biomarkers, Tumor↗

PubMed1995

Cellular death in neuroblastoma: in situ correlation of apoptosis and bcl-2 expression.

Apoptosis is the selective physiologic deletion of cells that are no longer required. Over-expression of the bcl-2 proto-oncogene extends survival of neurons otherwise destined for apoptosis. The unique capacity of neuroblastoma (NB) to undergo spontaneous regression and the prognostic dichotomy of children with this malignancy led us to evaluate bcl-2 expression and apoptosis in NB. An in situ DNA nick-labeling technique to detect apoptotic cells, as well as immunohistochemistry and morphology, were utilized in a selection of NB tumor specimens and in the human fetal sympathetic nervous system. bcl-2 expression was present in all 28 NB tumors examined and in sympathetic ganglia of the human fetus. Measurement of overall bcl-2 expression and of extent of apoptosis correlated with favorable prognosis. In low-stage tumors, bcl-2 expression was most intense in poorly differentiated tumor cells adjacent to fibrovascular stroma. Cells distant from the stroma exhibited increasing degrees of chromaffin differentiation, with apoptosis most evident in bcl-2-negative neuroblasts adjacent to well-differentiated NB cells. The spatial distribution of bcl-2 expression, apoptosis and chromaffin differentiation in favorable-prognosis NB may provide insight into mechanisms of persistent tumor existence or regression.

Apoptosis↗

PubMed1995

Proliferation and apoptosis in neuroblastoma: subdividing the mitosis-karyorrhexis index.

The Shimada classification is a frequently used, histopathological classification system for neuroblastoma tumours. Tumours are classified as prognostically favourable or unfavourable based upon stroma content, degree of neuroblastic maturation and patient age at diagnosis. The mitosis-karyorrhexis index is introduced in this classification system, as the cellular density sum of mitotic and karyorrhectic cells in the tumour. The biological nature of karyorrhectic cells is uncertain, but a high mitosis-karyorrhexis index in stroma-poor tumours is an indicator of poor prognosis. In this study, neuroblastoma tumours were analysed for cell proliferation, using antiproliferating cell nuclear antigen (PCNA) immunohistochemistry, and apoptosis, by morphology and in situ end-labelling of fragmented DNA. The karyorrhectic cells described in the Shimada classification were shown to be either proliferating or undergoing apoptosis. It is further shown that a high cellular density of proliferating cells correlates with poor prognosis, whereas a high density of apoptosis, in contrast, indicates favourable outcome.

Apoptosis↗

PubMed1995

Differentiation and survival influences of growth factors in human neuroblastoma.

Human neuroblastoma cell lines are established from high-stage, highly malignant tumours. Despite this and the fact that these tumours are arrested at an early, immature stage, many cell lines have the capacity to undergo neuronal differentiation under proper growth conditions. One such cell line is the noradrenergic SH-SY5Y cell line. These cells can be induced to mature by a variety of modalities, resulting in different mature phenotypes. The use of this cell system as a model to study the stem cell character of neuroblastoma is reviewed and discussed. In particular, we focus on growth factor dependencies in the SH-SY5Y system, and compare that to the normal situation, i.e. growth factor control of sympathetic neuronal and neuroendocrine differentiation during human and rat embryogenesis.

Cell Differentiation↗

PubMed1995

Association of neurotrophin receptor expression and differentiation in human neuroblastoma.

Interactions of the trk family of tyrosine kinase receptors with neurotrophins result in growth and maturational changes in neuronal cells. The continued progression, maturation, or regression of neuroblastoma, an embryonal, sympathetic nervous system-derived tumor of infants and children, might be governed by neurotrophic influences. Immunocytochemistry was utilized to evaluate TrkA, TrkB, and TrkC protein expression at the cellular level in the developing human fetal sympathetic nervous system and in a selection of neuroblastoma tumor specimens. TrkA and TrkC expression was identified in sympathetic ganglia and within the adrenal medulla, with intense TrkB expression restricted to paraganglia, of the normal developing human sympathetic nervous system. In neuroblastoma, pp140trkA expression correlated positively with favorable tumor stage (P = 0.0027) and favorable outcome (P = 0.026). No statistically significant correlation of TrkC expression with outcome was evident; however, both TrkA and TrkC expression was most apparent in tumor cells of increased differentiation. TrkB expression was primarily localized to cells within the fibrovascular tumor stroma. A model of neurotrophin receptor expression and neurotrophin reactivity with differentiation is proposed. The existence and spatial distribution of neurotrophin receptors in neuroblastoma lend supportive evidence that neurotrophic influences may be involved in tumor persistence or regression.

Adrenal Medulla↗

PubMed1995

IGF2 expression is a marker for paraganglionic/SIF cell differentiation in neuroblastoma.

Neuroblastoma is a childhood tumor of the sympathetic nervous system. Observations in the Beckwith-Wiedemann syndrome suggest that sympathetic embryonal cells with an abundant expression of the insulin-like growth factor 2 gene (IGF2) may be involved in the genesis of low-malignant infant neuroblastomas. We have therefore compared the cell type-specific IGF2 expression of the human sympathetic nervous system during early development with that of neuroblastoma. An abundant expression in normal sympathetic tissue was specific to extra-adrenal chromaffin cells, ie, paraganglia and small intensely fluorescent (SIF) cells, whereas sympathetic neuronal cells were IGF2-negative. A subpopulation of neuroblastomas expressed IGF2, which correlated with an early age at diagnosis, an extra-adrenal tumor origin, and severe hemodynamic signs of catecholamine secretion. Histologically IGF2-expressing tumors displayed a lobular growth pattern, and expression was restricted to the most mature and least proliferative cells. Typically, these cells were morphologically and histochemically similar to paraganglia/SIF cells and formed distinct ring-like zones in the center of the lobules around a core of apoptosis-like tumor cells. The similarities found between IGF2-expressing neuroblastoma cells and paraganglia/SIF cells in terms of histological features, anatomical origin, and age-dependent growth suggest a paraganglionic/SIF cell lineage of most infant tumors and also of extra-adrenal tumors diagnosed after infancy. Furthermore, since paraganglia/SIF cells undergo postnatal involution, the same cellular mechanism may be responsible for spontaneous regression in infant neuroblastoma.

Biomarkers, Tumor↗

PubMed1994

Development of invasive adenocarcinoma following colectomy with ileoanal anastomosis for familial polyposis coli. Report of a case.

PURPOSE: Proctocolectomy with ileoanal anastomosis has gained increasing acceptance for the prophylactic treatment of patients with familial polyposis coli. Long-term surveillance of the ileal pouch and the pouch-anal anastomosis has not been emphasized despite concern regarding retained rectal mucosa following the procedure. METHODS: A 34-year-old patient with a strong family history of familial polyposis coli was treated at 14 years of age by single-stage proctocolectomy with straight ileoanal anastomosis. Follow-up proctoscopic examinations revealed development of adenomatous changes at the ileoanal anastomosis. RESULTS: This report presents a patient with familial polyposis coli who developed invasive adenocarcinoma at the ileoanal anastomosis 20 years after proctocolectomy with ileoanal anastomosis. CONCLUSIONS: We stress the need for lifelong proctoscopic surveillance in patients with familial polyposis coli treated by proctocolectomy with ileoanal anastomosis.

Adenocarcinoma↗

PubMed1994

Congenital microgastria.

Congenital microgastria is an extremely uncommon dysplasic condition of the newborn stomach. With only 26 well-documented accounts of this anomaly reported in the literature, its treatment and long-term outcome have not been well elucidated. Herein, the authors report on a newborn with multiple congenital anomalies who presented with severe reflux and aspiration. The workup showed congenital microgastria. The infant's diagnostic and treatment course is described.

Abnormalities, Multiple↗