Comparative histological analysis of spleens in pediatric patients with hemolytic anemias: Insights into the pathophysiological mechanisms of spleen destruction in sickle cell anemia.

While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused ß-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy-Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis. Quantification on digitalized slides of iron deposition, RBC trapping, and red pulp fibrosis was additionally performed. Spleens from 22 children with SCA, eight with HS, eight with TDT, and three healthy controls (HC) were analyzed. Median age at splenectomy was not different between SCA and HS patients, 6.05 years (range: 4.5-16.0) versus 4.75 (range: 2.2-9.5). Marked heterogeneity was found in SCA spleens in contrast to other conditions. Contrary to previous reports, B-cell follicles were generally preserved in SCA. While RBC trapping was significantly increased in both SCA and HS (compared to TDT and HC), quantitative fibrosis and overall red pulp severity score were significantly increased in SCA spleens compared to other conditions. Moreover, there was an inverse correlation between quantitative fibrosis and number of B-cell follicles, linking these two compartments as well as spleen fibrosis to infectious susceptibility in SCA, potentially through impaired red pulp macrophage scavenging and B-cell subpopulations defects.

Collagenous gastritis in children: A national cohort.

BACKGROUND: Collagen gastritis is a rare disease that manifests in children mainly as isolated gastric involvement associated with martial deficiency anemia. There are no recommendations for the management and follow-up of these patients. We aimed to describe the clinical data, endoscopic findings, and treatments deployed in France's children with collagenous gastritis. METHODS: All French pediatric gastroenterology centers and pediatric centers for rare digestive diseases (Centres de Maladies Rares Digestives) were contacted to collect cases of collagenous gastritis, defined on gastric biopsies and diagnosed before 18 years of age. RESULTS: A total of 12 cases diagnosed (4 males and 8 females) between 1995 and 2022 could be analyzed. The median age at diagnosis was 12.5 years (7-15.2). The most frequent clinical presentation was abdominal pain (6/11) and/or nonspecific symptomatology attributed to anemia (8/10). Anemia was present in all children (11/11; Hb 2.8-9.1 g/dL). Nodular gastritis was present in 10 patients (antrum: 2; fundus: 4; in antrum and fundus: 4). All patients had a basement membrane thickening (from 19 to 100 µm). The treatments received were PPI (11), oral or intravenous martial supplementation (12), budesonide (1), and prednisone (1). Martial supplementation improved anemia in all cases. At discontinuation, nine of 10 patients had a recurrence of anemia. CONCLUSION: Collagenous gastritis is an exceptional condition, clinically manifested in children as abdominal pain and iron deficiency anemia probably of hemorrhagic origin. Patients require long-term follow-up and monitoring of their disease to describe the risk of progression better.

Complications and Disease Recurrence After Ileocecal Resection in Pediatric Crohn's Disease: A Retrospective Study.

OBJECTIVE: The aim of this retrospective study was to describe the risk of postoperative recurrence (POR) after ileocecal resection, the occurrence of surgical complications, and identify predictors of these adverse postoperative outcomes in pediatric Crohn's disease (CD). PATIENTS AND METHODS: All the children less than 18 years of age with a diagnosis of CD, who underwent primary ileocecal resection for CD between January 2006 and December 2016 in our tertiary center, were considered for inclusion. Factors related to POR were investigated. RESULTS: A total of 377 children were followed for CD between 2006 and 2016. During this period, 45 (12%) children needed an ileocecal resection. POR was diagnosed in 16% (n = 7) at 1 year and 35% (n = 15) at the end of the follow-up, with a median follow-up of 2.3 years (Q1-Q3 1.8-3.3). Median duration of the postoperative clinical remission was 1.5 years (range 0.5-2). Multivariate Cox regression analysis identified only young age at diagnosis as a risk factor for POR.In total, 7 of the 43 patients (16%) developed severe postoperative complications, defined as requiring surgical, endoscopic, or radiological intervention. The only risk factor was intraoperative abscess. CONCLUSION: Only young age at diagnosis was associated with POR. This information could be useful to develop targeted therapeutic strategies for young CD children. At the end of follow-up with a median follow-up of 2.3 years (Q1-Q3 1.8-3.3), there was no surgical POR: endoscopic dilatation for POR should be considered in order to delay or prevent surgery.

Congenital central hypoventilation syndrome and Hirschsprung disease: A retrospective review of the French National Registry Center on 33 cases.

AIM OF THE STUDY: Congenital Central Hypoventilation Syndrome (CCHS) is a rare affection associated to Hirschsprung disease (HD) in 20% of the cases. Using the French CCHS registry, we described the population of patients suffering from both CCHS and HD reporting the outcome on these patients. METHODS: Medical records were reviewed. Epidemiological, clinical, histological and genetic data were analyzed and extracted from the national French registry data. RESULTS: 33 patients had CCHS and HD. Thirty percent had a severe form of CCHS (Death owing to CCHS or 24/24 ventilation beyond 1 year old). Fifty four percent required tracheotomy. HD's pathologic segment was classic (Rectosigmoid and left colic form) in 20% and long (Above the splenic flexure) in 80%. Twenty four percent were treated with daily irrigation, 21% had colostomy without undergoing pullthrough, and 55% underwent optimal treatment (pull through). We failed to demonstrate a correlation between severity of CCHS and HD's length. The rate of mortality was 57% and was higher in the long HD group (p = 0.0005). Fourteen patients were still alive, aged 1 to 31 years old. Ninety two percent were weaned off the 24/24 ventilation. Regarding the intestinal function, 38% presented with soiling and 30% with chronic diarrhea. Hundred percent had CCHS follow-up while only 35% had no surgical follow-up in regard to the HD. CONCLUSIONS: This is the largest study regarding the CCHS / HD association and its long-term followup. Mortality is high demonstrating that a multidisciplinary follow-up on respiratory and intestinal function is necessary to improve outcome. Level III study.

Indications and results of diagnostic biopsy in pediatric renal tumors: A retrospective analysis of 317 patients with critical review of SIOP guidelines.

OBJECTIVES: According to the Renal Tumor Study Group (RTSG) of the International Society of Paediatric Oncology (SIOP), diagnostic biopsy of renal tumors prior to neoadjuvant chemotherapy is not mandatory unless the presentation is atypical for a Wilms tumor (WT). This study addresses the relevance of this strategy as well as the accuracy and safety of image-guided needle biopsy. METHODS: Clinical, radiological, and pathological data from 317 children (141 males/176 females, mean age: 4 years, range, 0-17.6) consecutively treated in one SIOP-affiliated institution were retrospectively analyzed. RESULTS: Presumptive chemotherapy for WT was decided for 182 patients (57% of the cohort), 24 (8%) were operated upfront, and 111 (35%) were biopsied at diagnosis. A non-WT was confirmed after surgery in 5/182 (3%), 11/24 (46%), and 28/111 (25%), respectively. Age at diagnosis was the most commonly (46%) used criterion to go for biopsy but a nine-year threshold should be retrospectively considered more relevant. Tumor volumes of clear cell sarcoma of the kidney and WT were significantly higher than those of other tumors (P = 0.002). The agreement between core-needle biopsy (CNB) and final histology was 99%. No significant morbidity was associated with CNB. CONCLUSION: The use of SIOP criteria to identify patients eligible for presumptive WT neoadjuvant chemotherapy or upfront surgery avoided biopsy in 65% of children and led to a 97% rate of appropriate preoperative chemotherapy. Image-guided CNB is a safe and accurate diagnostic procedure. The relevance of SIOP biopsy criteria might be improved by using an older age threshold (9 years instead of 6 years) and by adding initial tumor volume.

Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease.

OBJECTIVE: There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations of intestinal microbiota (IM) have been reported in alcoholic liver disease (ALD), but the extent to which they are merely a consequence or a cause is unknown. We aimed to demonstrate that a specific dysbiosis contributes to the development of alcoholic hepatitis (AH). DESIGN: We humanised germ-free and conventional mice using human IM transplant from alcoholic patients with or without AH. The consequences on alcohol-fed recipient mice were studied. RESULTS: A specific dysbiosis was associated with ALD severity in patients. Mice harbouring the IM from a patient with severe AH (sAH) developed more severe liver inflammation with an increased number of liver T lymphocyte subsets and Natural Killer T (NKT) lymphocytes, higher liver necrosis, greater intestinal permeability and higher translocation of bacteria than mice harbouring the IM from an alcoholic patient without AH (noAH). Similarly, CD45+ lymphocyte subsets were increased in visceral adipose tissue, and CD4(+)T and NKT lymphocytes in mesenteric lymph nodes. The IM associated with sAH and noAH could be distinguished by differences in bacterial abundance and composition. Key deleterious species were associated with sAH while the Faecalibacterium genus was associated with noAH. Ursodeoxycholic acid was more abundant in faeces from noAH mice. Additionally, in conventional mice humanised with the IM from an sAH patient, a second subsequent transfer of IM from an noAH patient improved alcohol-induced liver lesions. CONCLUSIONS: Individual susceptibility to ALD is substantially driven by IM. It may, therefore, be possible to prevent and manage ALD by IM manipulation.

Two congenital cases of pigmented epithelioid melanocytoma studied by fluorescent in situ hybridization for melanocytic tumors: case reports and review of these recent topics.

The term 'pigmented epithelioid melanocytoma' (PEM) has recently been proposed as a nosological framework grouping lesions formerly known as animal-type melanomas, sporadic epithelioid blue nevi and Carney complex-associated epithelioid blue nevi. Congenital PEMs have been reported extremely rarely and their prognosis is poorly known. Four-color fluorescent in situ hybridization (FISH) for melanocytic lesions is a recent method developed to assess the malignant potential of ambiguous melanocytic lesions. Here we describe 2 cases of congenital epithelioid and strongly pigmented melanocytic lesions consistent with PEM. No BRAF gene mutation was found in the 2 cases. FISH for melanocytic lesions was also performed. The first case proved entirely negative, whereas the second one showed a positive zone with an extra copy of chromosome 6. The prognosis and management of PEM are discussed, with a review of the available data on the history, demographics, molecular alterations and histopathological aspects of this entity. PEM seems to represent a unique low-grade melanocytic tumor with a limited potential of metastasis to lymph nodes, but a favorable long-term clinical course. The published data about FISH for melanocytic tumors, and especially PEM, are reviewed. Four-color FISH may be a useful tool to assess more accurately the prognosis of these tumors.

Is laparoscopic management suitable for solid pseudo-papillary tumors of the pancreas?

PURPOSE: Solid pseudo-papillary tumors (SPT) are rare pancreatic neoplasms of low-malignant potential occurring mainly in young women. The purpose of this report is to describe our experience with laparoscopic management of these tumors with 4-year follow-up. METHODS: Three children with SPT were admitted to two hospitals in Paris, France, between February 2000 and December 2006. Diagnosis or treatment was carried out using laparoscopic techniques (biopsy and resection in one case and biopsy only in two). Long-term follow-up data were collected. RESULTS: All three patients presented recurrences within 3 years after resection, i.e., disseminated peritoneal recurrence in two patients and local recurrence in one. The two patients with peritoneal recurrences were treated by surgical resection and chemotherapy. The patient with local recurrence could not be treated due to contraindicating local factors. All three patients were alive at the time of this writing. CONCLUSION: This is the first report describing long-term follow-up after laparoscopic management of SPT. All three patients developed recurrences. These poor results contrast sharply with the low risk of local or disseminated recurrence after open laparotomy without chemotherapy that has been considered as the treatment of choice up to now. Recurrences after laparoscopic management may have been due to diffusion of tumor cells caused by gas insufflation especially during biopsy. Laparoscopic biopsy should not be performed in patients presenting SPT.

[Hemorrhagic ascites revealing duodenal duplication]. / Une ascite hémorragique révélant une duplication duodénale.

Duodenal duplication is a rare congenital disorder of the gastrointestinal tract. The presentation is highly variable. We report a case of duodenal duplication presenting with hemorrhagic ascites in a 3-month-old girl. The diagnosis of duodenal duplication can be made preoperatively by resonance magnetic imaging. Surgical resection of the duplication was performed. Microscopic examination of the specimen confirmed the duodenal duplication. To our knowledge, this is the 1st reported case of hemorrhagic ascites caused by duodenal duplication and demonstrated by resonance magnetic imaging.

Leukocytes and the kidney contribute to interstitial inflammation in lupus nephritis.

Interstitial leucocyte infiltration, a prominent feature of lupus nephritis, predicts deterioration of renal function. We used two models of lupus nephritis in mice, one with chronic spontaneous disease and the other with acute interferon-alpha (IFN alpha)-mediated disease. The latter is characterized by the virtual absence of interstitial infiltration. In vivo migration assays showed that splenic leukocytes from spontaneously nephritic mice tended to migrate into non-inflamed syngeneic kidneys. This was enhanced if the recipient kidneys were already inflamed. Kidneys from both chronically and acutely nephritic mice showed similar ability to recruit splenic leukocytes from chronically diseased mice. Leukocytes from acutely diseased mice, however, failed to migrate into chronically inflamed kidney. Compared with those with chronic nephritis, the kidneys of acute nephritic mice expressed less of the inflammatory chemokine CXCL13/BLC. Moreover, leukocytes from acute nephritic mice displayed impaired migration, in vitro, to T-cell chemokine attractants. This study links leukocyte infiltration to both kidney chemokine expression, and leukocyte chemotaxis to kidney-expressed chemokines.

Abdominal lymphangiomas in children: interest of the laparoscopic approach.

BACKGROUND: Lymphangiomas are rare benign lesions of the lymphatic system. The most common symptoms are abdominal tumor or "acute abdomen" in children. The treatment of choice is complete surgical resection, but the recurrence rate with incomplete resection is high, and laparotomy exposes the patient to adhesions. The authors report their experience with the lymphangioma laparoscopic approach. METHODS: This retrospective study examined 15 consecutive operations for lymphangiomas in children, ages 5 months to 14 years, treated during the 5-year period from 1999 to 2004. RESULTS: Six patients were treated using the primary laparotomy approach, and nine patients underwent the laparoscopic procedure, six successfully. Three conversions were necessary (1 case requiring partial colectomy, 1 retroperitoneal case with adherence on the aorta and vena cava, 1 case with partial volvulus). Morbidity included two cases of acute occlusion caused by adhesions after laparotomy. There was no recurrence of lymphangioma during a mean follow-up period of 35 months. CONCLUSION: The laparoscopy procedure could be used successfully for abdominal lymphangioma, even in an emergency. When the laparoscopic resection is impossible, laparotomy or sclerotherapy can be discussed.

[Rhabdomyosarcoma of the genitourinary sinus in children]. / Rhabdomyosarcomes du sinus urogénital de l'enfant.

Genitourinary rhabdomyosarcoma (RMS) accounts for approximately 25% of all rhabdomyosarcomas. Management of RMS at this site has changed during the last 5 consecutive Intergroup Rhabdomyosarcoma (IRS) trials, with increasing emphasis of bladder and vaginal conservation. As more effective treatment regimens has improved survival, surgical approaches have evolved to less aggressive management of the primary tumour to improve conservation. Various combinations of chemotherapy, irradiation and surgery have resulted in a decreased late sequelae in the group of patients with sarcoma arising in the genitourinary tract.

Crohn's disease in children. Preliminary experience with a laparoscopic approach.

BACKGROUND: Laparoscopic surgery in patients with Crohn's disease (CD) has been demonstrated to have advantages over a conventional approach in children. The aim of this study was to review the children treated for CD with a laparoscopic approach, to report our indications, the surgical procedure, the complications, and to compare the children with pancolitis or ileocaecal (segmental) Crohn's disease. PATIENTS AND METHOD: We reviewed the files of 11 children treated for CD in a single institution between 1999 and 2004 for a retrospective study of clinical and surgical data. Mann-Whitney U-test was used for statistical analysis of nonparametric data. RESULTS: Eleven children were operated. The average age when initial clinical symptoms became apparent was 12.1 years (range 6.6 - 15), and surgery was performed after an average of 3.4 years of disease (range 1 - 7.6). The surgical indications were stenosis in 6 cases, failure to thrive in 1 case (segmental CD, SCD group) and pancolitis refractory to medical treatment in 4 cases (pancolitis group, PCD group). Mean operative time was 207 minutes (range 140 - 270) for the SCD group and 285 minutes (range 260 - 300) for the PCD group (p < 0.05). Three cases needed a conversion to open surgery (2 in PCD group, one in SCD group), mainly in relation to anastomosis performed with an EEA stapler. The average length of surgical unit stay was 6.5 days (range 4 - 8) for the PCD group and 6.4 days (range 4 - 8) for the SCD group; average follow-up was 16 months (range 3 - 38). Two patients had a relapse of CD (stenosis of the anastomosis in one, skin fistula in the other). CONCLUSION: A laparoscopic approach for ileocolic resection in Crohn's disease is a feasible procedure, even in cases of pancolitis. We recommend an extra-corporeal anastomosis because, in relation to the inflammatory bowel, the mechanical anastomosis is not a safe procedure in cases of pancolitis.

Laparoscopic distal pancreatectomy for Frantz's tumor in a child.

Solid pseudopapillary tumor of the pancreas is a rare pathologic entity. Although the role of laparoscopy in surgery of the pancreas is still controversial, laparoscopic distal pancreatectomy has been reported with good results in adults. We report a laparoscopic spleen-preserving distal pancreatectomy in a 9-year-old boy who presented with a low-grade malignant tumor. Needle biopsy was impossible. A laparoscopic spleen-preserving distal pancreatectomy was performed. We used four trocars, and the operative time was 240 min. Conversion to open surgery was not necessary. The boy's postoperative recovery was uneventful, and he was discharged on the 6th day. CT-scan control at 6 months was normal. This case shows that even in advanced surgical cases, such as spleen-preserving distal pancreatectomy, laparoscopic procedures can be done safely, within a reasonable operative time, in children.

Cytokines, chemokine receptors, and homing molecule distribution in the rectum and stomach of pediatric patients with ulcerative colitis.

BACKGROUND: Cytokines appear to play a significant role in the pathogenesis of inflammatory bowel disease (IBD) with a predominant Th2 pattern in colonic mucosa of patients with ulcerative colitis (UC). Chemokines and their receptors also regulate the migration of Th1 or Th2 lymphocytes to inflammatory tissues during the immune response. Although adult UC is usually confined to the colon, pediatric UC not uncommonly affects the stomach. AIMS: The aim of this study was to compare expression of cytokines, chemokine receptors, and homing molecules in the rectal and the histologically characterized gastric mucosa of pediatric patients with UC. SUBJECTS Sixteen patients (11 girls and 5 boys; median age, 9 years) having all the features of UC were included in the study. METHODS: Rectal and gastric mucosa obtained from UC cases were immunostained with antibodies against L-selectin, beta 7 integrin, CXCR3, CCR3, and CCR5. IL-4 and IL-12 p40 transcript expression was studied by in situ hybridization. RESULTS: Chronic gastritis was found in 93.7% of cases and Helicobacter pylori (Hp) was found in 2 (13.3%) cases. In the rectal and gastric mucosa, CXCR3 was found in perivascular lymphocytes and CCR5 in a subset of CXCR3+ cells in the lamina propria. CCR3+ lymphocytes and IL-4-positive cells were always found, but there was no evidence of IL-12 production. Most of the lymphocytes infiltrating the gastric mucosa expressed beta 7 but not CD62L. In contrast, beta 7-positive cells were randomly dispersed in the rectal lamina propria, and the fraction of CD3+beta 7+ was low. CONCLUSIONS: The authors conclude that gastritis is common in pediatric UC. The presence of CCR3+ lymphocytes, IL-4 transcript expression, without IL-12 p40 production in the stomach and in the rectum suggests a Th2 immune response. The presence of CCR3+, CD62L- activated Th2 cells may suggest that these gastric cells are recruited from colorectal primary lesions.

Laparoscopic adrenal surgery for neuroblastomas in children.

PURPOSE: The role of laparoscopy in children with neuroblastomas has not been fully defined. The laparoscopic approach to the adrenal gland is already largely used in adults and a few cases have been reported in children. We report the experience of a single surgical team center with laparoscopic adrenal surgery for neuroblastomas in children. MATERIALS AND METHODS: Between September 2000 and October 2002 laparoscopic adrenalectomy for neuroblastoma was performed in 9 patients (6 girls and 3 boys) with a mean age of 38 months (range 2 months to 9 years). Two tumors were detected prenatally and 7 postnatally. Preoperative diagnosis was neuroblastoma stage I in 4 cases and stage IV in 3 cases, and nondetermined suprarenal calcified masses in 2 cases. A 4 or 5-trocar transperitoneal approach was used in all cases. The adrenal tumors were completely excised, placed into a plastic bag and removed through the umbilical trocar site. RESULTS: All of the adrenal tumors were well encapsulated and completely excised. One of the 9 procedures was converted to open surgery because of adhesions to renal vessels. In 1 case a second hepatic localization was removed simultaneously, and in 3 cases 1 or more lymph nodes were resected. Average operative time was 85 minutes (range 45 to 170). There were no deaths. There were no postoperative complications, except 1 port site infection that was treated locally. Blood transfusion was not required. Average hospital stay was 4.5 days (range 2 to 10). Histological analysis of the 9 specimens (maximum length 6 cm) confirmed the diagnosis of neuroblastoma. N-myc status was studied in 8 of the 9 resected neuroblastomas and was amplified in 2 cases (both stage IV with preoperative biopsy). Average postoperative followup was 15 months (range 1 to 25). There was no local recurrence or metastasis, except in the case that required conversion to open surgery (local recurrence 7 months later). CONCLUSIONS: Laparoscopic adrenalectomy for neuroblastoma is safe and feasible in children, with good results. Experience with advanced laparoscopic surgery is required to achieve this result in optimal oncological conditions. Our short-term results must be reevaluated at long term, and further studies are needed to compare laparoscopy to open surgical techniques.

Card15 gene overexpression in mononuclear and epithelial cells of the inflamed Crohn's disease colon.

BACKGROUND: Crohn's disease is one of the principal human chronic inflammatory bowel diseases. Although its aetiology is still unknown, its complex pathogenesis has environmental, immunological, and genetic determinants. CARD15 is the first susceptibility gene implicated in the predisposition to Crohn's disease and is known to be expressed only in monocytes. However, its expression in situ has not yet been studied. AIMS: To analyse the tissue distribution of CARD15 and identify cells producing CARD15 in samples of colon from patients with Crohn's disease and control subjects. PATIENTS AND METHODS: We analysed CARD15 gene expression in surgical specimens of colon from eight children with Crohn's disease and nine controls by immunohistochemistry, in situ hybridisation, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: We showed that CARD15 was present only in the cytoplasm of macrophages in the normal colon. Increased CARD15 expression was detected in Crohn's disease lesions. There were more CARD15 positive cells in Crohn's disease lesions than in uninvolved areas. Both intestinal epithelial cells, macrophages, and their derivatives overproduced CARD15 in Crohn's disease. To further assess CARD15 expression by intestinal epithelial cells, we performed RT-PCR on freshly isolated intestinal epithelial cells, and showed that these cells isolated from Crohn's disease samples contained more CARD15 mRNA than intestinal epithelial cells from controls. CONCLUSIONS: We have demonstrated that colonic involvement in active Crohn's disease is associated with increased CARD15 gene expression in both macrophages and intestinal epithelial cells. Therefore, this deregulation can affect the host-environment interaction and thus contribute to the pathogenesis of this disease.

Follow-up of partial splenectomy in children with hereditary spherocytosis.

BACKGROUND/PURPOSE: The aim of this report is to study the short- and long-term consequences of partial splenectomy (PS) in hereditary spherocytosis (HS). METHODS: The authors reviewed the files of 5 children who underwent PS from 1993 to 1998. The data collected included clinical presentation, age, gender, indication for the operation, radiographic examination, need for blood transfusion and hematologic values, description of surgical procedure, and early- and late-occurring complications. RESULTS: From 1993 to 1998, 5 children from one year, 9 months to 7 years of age underwent PS. Indications were hypersplenism and severe anemia. The average age at the time of the operation was 3 years, 5 months. The 2 youngest children (one year, 9 months and 2 years old) needed a second operation because of the recurrence of hypersplenism. CONCLUSIONS: Subtotal splenectomy seems to preserve the immune role of the spleen and can reduce the need for blood transfusion. But PS is associated with a regrowth of the splenic remnant in children suffering from chronic hemolysis with hypersplenism and seems to be effective for a relatively short period only, especially in young children. Thus, a second operation to perform a total splenectomy can be necessary. The decision to perform a PS on young children with HS as an alternative to total splenectomy with appropriate preoperative vaccination and postoperative prophylactic antibiotics therefore should be weighed carefully, keeping in mind, however, the benefit of postponing total splenectomy in these patients.

The IGF system in neuroblastoma xenografts: focus on IGF-binding protein-6.

With a view to investigating the implication of IGF-binding protein-6 (IGFBP-6) in the growth of neuroblastomas, nude mice were injected with IGFBP-6-expressing or control IGR-N-91 human neuroblastoma cells and the resulting xenografts examined. Expression of IGFBP-3, IGFBP-4 and type 1 and type 2 IGF receptor messengers was similar in control tumours and equal-sized IGFBP-6-expressing tumours that had developed. IGF-II was more strongly expressed in control tumours, and IGFBP-6-expressing tumours contained less IGFBP-2 than controls. In both populations, there was a significant positive correlation between IGF-II and IGFBP-2 expression. In small IGFBP-6-expressing xenografts where tumour development had apparently been arrested, haematoxylin--eosin and TUNEL staining revealed numerous apoptotic cells. In situ hybridization indicated homogeneous distribution of the IGFBP-6 signal in test tumours. In cell culture, IGFBP-6-expressing cells expressed similar amounts of IGFBP-2, IGF-II and N-myc mRNAs as control cells; but media conditioned by IGFBP-6-expressing cells contained less intact IGFBP-2 protein, with no increase in its proteolytic fragment. In media treated with plasminogen, in which IGFBP-2 was proteolysed, IGFBP-6 was increased. With its especially strong affinity for IGF-II and its resistance to proteolysis, IGFBP-6 would act by sequestering IGF-II, hence inhibiting its mitogenic and anti-apoptotic effects. In excess, IGFBP-6 would displace IGF-II from IGFBP-2 whose potentiation of IGF-II action would cease and whose susceptibility to degradation would be increased. This study therefore shows that IGFBP-6 plays a role in neuroblastoma cell growth in vivo and in vitro and that stable overexpression of IGFBP-6 leads to alteration of the initial balance between the IGFBPs.