Prevalence and risk factors for diastasis recti abdominis: a review and proposal of a new anatomical variation.

PURPOSE: Diastasis recti abdominis (DRA) or rectus diastasis is an acquired condition in which the rectus muscles are separated by an abnormal distance along their length, but with no fascia defect. To data there is no consensus about risk factors for DRA. The aim of this article is to critically review the literature about prevalence and risk factor of DRA. METHOD: A total of 13 papers were identified. RESULTS: The real prevalence of DRA is unknown because the prevalence rate varies with measurement method, measurement site and judgment criteria, but it is certainly an extremely frequent condition. Numbers of parity, BMI, diabetes are the most plausible risk factors. We identified a new anatomical variation in cadaveric dissection and in abdominal CT image evaluation: along the semilunar line the internal oblique aponeurosis could join the rectus sheath with only a posterior layer, so without a double layer (anterior and posterior) as usually described. We conducted a retrospective review of abdominal CT images and the presence of the posterior insertion only could be considered as a risk factor for DRA. CONCLUSION: Further studies with large sample size, including nulliparous, primiparous, pluriparous and men too, are necessary for identify the real prevalence.

An extraperitoneal approach for complex flank, iliac, and lumbar hernia.

PURPOSE: The aim of this paper is to propose our four-step technique, an open extraperitoneal approach for complex flank, lumbar, and iliac hernias. METHODS: A big polypropylene mesh is placed, covering and reinforcing all the lateral abdominal wall in an extraperitoneal space. Its borders are retroxiphoid fatty triangle and the costal arch cranially and the retropubic space caudally, psoas muscle, and paravertebral region posteriorly and contralateral rectus muscle medially. Mesh dimensions do not depend from the defect size, but prosthesis has to cover all the lateral abdominal wall. RESULTS: No major complications have been reported. The mean length of stay is 4.8 days (range 3-11). Mean follow-up is 44.8 months (range 5-92). One recurrence (4.5%) has been reported at the 1-year clinical evaluation. CONCLUSION: In conclusion, we believe that regardless size and location of the defect, every complex lateral hernia requires the same extensive repair because of the critical anatomy of the region with a big medium-heavyweight polypropylene mesh placed in an extraperitoneal plane, the only one that allows adequate covering of the visceral sac. Our technique is a safe, feasible, and reproducible treatment for this challenging surgical problem.

Treatment of pediatric non-Hodgkin lymphomas in a country with limited resources: results of the first national protocol in Nicaragua.

We report the results of a protocol for the diagnosis and treatment of pediatric non-Hodgkin lymphomas (NHL) conducted in Nicaragua in the context of an international collaborative program. Fifty-three children with NHL treated between 1996 and 2003 were retrospectively evaluated. Therapy was designed based on local drug availability and affordability with dose and schedule adaptations for Burkitt and lymphoblastic lymphomas. With a median follow-up of 3 years, the projected 9-year overall survival was 63% and event-free survival 53%. The treatment was efficacious, feasible, and well tolerated in spite of the local socio-economical conditions.

Home care for children following haematopoietic stem cell transplantation.

The quality of life of patients who undergo haematopoietic stem cell transplantation (HSCT) is affected by long periods of hospitalisation for the treatment of several complications. On this basis, 28 children who underwent 29 HSCTs were included in the Home Care (HC) programme of the Paediatric Haematology and Oncology Department of the Gaslini Children's Hospital to be discharged earlier. A total of 17 children were assisted for haematologic follow-up and support therapy administration. The remaining children were followed up for graft- versus-host disease and/or cytomegalovirus infection. Overall activity consisted of 1232 i.v. therapies, 501 blood tests, 58 red blood cell or platelet transfusions, 107 procedures on Central Venous Catheter. Median duration of the assistance per child was 25 days (range 1235) for a total of 1598 days. A total of 822 accesses at home replaced 459 and 363 out-patient and in-patient days of hospitalisation. The average cost per patient receiving HC (EUR 4,252) was significantly lower (P<0.01) when compared to the average cost per patient admitted to the hospital to undergo the same procedures (EUR 14,693). This report shows that HC is feasible for children following HSCT, that it reduces the discomfort of the patients and their families, and that it reduces costs.

Bone marrow transplant indications for childhood leukemias: achieving a consensus. The EBMT Pediatric Diseases Working Party.

During the "2nd International Course on Bone Marrow Transplantation in Children" a multiple choice questionnaire on bone marrow transplant indications for children with acute leukemias was distributed with the aim of achieving a consensus. The answers obtained from the twenty representatives of fourteen European countries during the meeting were analyzed and assigned to one of the following groups: I. definitive indication: when more than 75% participants were in favour; II. acceptable indication: when 50% to 74% participants were in favour; III. requires further investigation: when 25% to 49% participants were in favour; IV. no indication: when less than 24% participants were in favour. In acute lymphoblastic leukemia the following circumstances were considered a definitive indication for allogeneic bone marrow transplant (BMT) from a matched sibling donor (MSD): infancy, "high risk" (HR) patients in 1st complete remission (CR1); CR2 patients after an early bone marrow relapse (defined as a relapse occurring up to six months after stopping therapy). Patients experiencing an early meningeal relapse and CR2 patients after a late relapse (defined as a relapse occurring later than six months after stopping therapy) were considered an acceptable indication. Further investigation was required in order to better define the role of BMT for patients experiencing an early isolated testicular relapse. If a MSD is not available, HR patients in CR1 and CR2 patients, after an early bone marrow relapse, were considered a definite indication for a matched unrelated donor (MUD). This latter group was considered an acceptable indication for a haploidentical BMT if a MUD was not available. Further investigation was required to better define the role of autologous bone marrow transplant (ABMT) for patients experiencing an early extramedullary relapse and for HR patients in CR1 all of whom lacked MSD's. In acute myeloblastic leukemia (AML), CR2 patients were considered a definitive indication and CR1 patients were considered an acceptable indication for BMT from a MSD. CR2 patients were considered a definitive indication for ABMT and CR1 patients an acceptable indication in cases lacking a MSD. AML was not considered an indication for MUD BMT.

Phase II study of recombinant human granulocyte colony-stimulating factor in children undergoing bone marrow transplantation.

Twenty-three children with congenital or acquired hematological disorders and 8 children with solid tumors received filgrastim at a dose of 5 micrograms/Kg by a daily 2-hour infusion following allogeneic (18 cases) or autologous (13 cases) bone marrow transplantation (group I). The results were compared with those of a disease, age and type of transplant matched cohort of 31 children treated in the same institution who did not receive the growth factor (group II). Filgrastim treatment was started within 24 hours of completion of the marrow infusion and lasted for 21 consecutive days or until the absolute neutrophil count reached 10 x 10(9)/l for 3 consecutive days. Twelve variables were evaluated prospectively in Group I and retrospectively in Group II. Myeloid reconstitution with peripheral granulocyte counts > 0.5 x 10(9)/L was achieved at a median time of 13 days in group I and of 14 days in group II (p = ns). Platelet recovery to > 50 x 10(9)/L was slower in group I (43 vs 30 days: p < .05). Median time to last platelet and red blood cell infusion was higher in group I (33 vs 18 days for platelets, p < .05; 45 vs 25 for red blood cells, p < .005). Filgrastim-treated children undergoing autologous BMT had fewer days of fever (6 vs 10 days, p < .05). There was no significant toxicity ascribable to filgrastim. Clinically and microbiologically documented infections, days of antibiotic therapy, duration of total parenteral nutrition and median time in hospital were similar in both groups. We conclude that in children undergoing autologous BMT for malignancies, filgrastim significantly reduced the number of febrile days. Similar benefits were not observed in children undergoing allogeneic BMT. Children receiving filgrastim experienced a delay in erythrocyte and platelet recovery. A prospective randomized study is required to better define the cost-benefit of filgrastim in children undergoing autologous or allogeneic BMT.

Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation.

Mycophenolate mofetil (MMF) is an alternative immunosuppressant which inhibits the proliferation of T and B lymphocytes. The purpose of the present study was to evaluate the safety and efficacy of MMF as salvage therapy for chronic GVHD (cGVHD) in children receiving allogeneic bone marrow transplantation. Fifteen children, 3-16 years of age, who had received grafts from HLA-compatible siblings (n = 8), partially matched related donors (n= 2) or matched unrelated donors (n = 5), developed extensive cGVHD which had proved unresponsive to standard immunosuppressive therapy. Patients were treated with MMF at the dose of 15-40 mg/kg/day in combination with other immunosuppressive therapy for a median of 4 months (range 1-15 months). The overall response rate (complete or partial response) was 60%. Thirteen percent had only minor responses, whereas 27% of patients had progressive disease. Best responses were seen in patients with GI tract (60% of complete responses) or mouth (33% of complete responses) cGVHD and skin involvement (43% of complete responses) that did not include sclerodermatous manifestations. Once MMF was started, improvements in the clinical manifestations of cGVHD allowed a significant reduction of steroids in 45% of patients and discontinuation in 27% of cases. Six patients (40%) experienced adverse events, with gastrointestinal symptoms predominating. Five patients experienced opportunistic infections. MMF was discontinued after 35-180 days in six patients for the following reasons: parents choice (n = 2), liver toxicity (n = 1), poor compliance (n = 2), and no response (n = 1). In conclusion, these preliminary results suggest that MMF in combination with other immunosuppressive agents may have a role to play in patients with cGVHD. Prospective clinical trials are needed to establish exact indications for therapy and dosage scheduling. Bone Marrow Transplantation (2000).

Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation.

Malignant autosomal recessive (AR) osteopetrosis represents an absolute indication for bone marrow transplantation (BMT). Over the last 15 years, almost 100 BMTs for osteopetrosis have been reported. The median age at transplant of most patients is 4 months. Very few cases of mild AR osteopetrosis have been described. Here, we report the good outcome of two cases of mild AR osteopetrosis with a follow-up of 5 and 6 years, respectively, after an HLA-identical sibling transplant undergone at 5 and 12 years of age, respectively. At the time of BMT, severe visual impairment was present in both children. Bone biopsy demonstrated hypermineralization with virtual obliteration of the medullary spaces, rare microfoci of hematopoiesis and marked deficiency in osteoclastic activity. Successful engraftment was complicated by hypercalcemia, controlled by a combination of bisphosphonate, phosphate infusions, vigorous hydration and calcitonin. Following BMT, radiological and histological findings showed extensive bone resorption with marked augmentation of the osteoclasts in normalized marrow. No improvement was observed in visual acuity, despite complete remodeling of skeletal abnormalities. We conclude that allogeneic BMT is the only chance of curing mild AR osteopetrosis.

Fiberoptic bronchoscopy and bronchoalveolar lavage for the evaluation of pulmonary infiltrates after BMT in children.

Thirty-one fiberoptic bronchoscopies and BAL performed within 4 days after the appearance of pulmonary infiltrates in 28 children who received BMT were reviewed. A causative agent was identified in 67% of patients with diffuse infiltrates (Cytomegalovirus in 8 cases, Pneumocystis carinii in 4) and in 31% of those with localized infiltrates (Aspergillus in 2, bacteria in 2). No relevant side effect was reported. The results obtained from cytological and microbiological testing provided relevant informations for the management of most cases, regardless to the identification of a specific pathogen. We conclude that BAL is a safe diagnostic procedure that should be considered early after the onset of pulmonary complications in BMT recipients.

Transplant-related toxicity and mortality: an AIEOP prospective study in 636 pediatric patients transplanted for acute leukemia.

Hematopoietic stem cell transplantation can cure high-risk acute leukemia (AL), but the occurrence of non-leukemic death is still high. The AIEOP conducted a prospective study in order to assess incidence and relationships of early toxicity and transplant-related mortality (TRM) in a pediatric population. Between 1990 and 1997 toxicities reported in eight organs (central nervous system, heart, lungs, liver, gut, kidneys, bladder, mucosa) were classified into three grades (mild, moderate, severe) and prospectively registered for 636 consecutive children who underwent autologous (216) or allogeneic (420) transplantation, either from an HLA compatible related (294), or alternative (126) donor in 13 AIEOP transplant centers. Overall, 47% of the patients are alive in CR (3-year EFS: 45.2%, s.e.: 2.1), 19% died in CR at a median of 60 days (90-day TRM: 14.3%, s.e.: 1.4), 34% relapsed. Toxicity of any organ, but mucosa and gut, was positively correlated with early death; moderate and severe toxicity to heart, lungs, liver and kidneys significantly increased early TRM, with estimated relative risks of 9.1, 5.5, 2.7 and 2.8, respectively, as compared to absent or mild toxicity. Patients with grade III-IV aGVHD experienced more than double (56% vs. 19%) TRM than patients with grade 0-II aGVHD. A higher cumulative toxicity score, estimating the impact of toxicity on TRM, was significantly associated with transplantation from an alternative donor. Quantitative assessment allowed us to describe the extent to which 'grade' of toxicity and 'type' of involved organs were related to mortality and pre-transplant characteristics and yielded a prognostic score potentially useful to compare different conditioning regimens and predict probability of early death.

Autologous bone marrow transplantation for extramedullary relapse in childhood leukemia. The AIEOP Group and the FONOP. Italian Association of Pediatric Hemato/Oncology.

The role of autologous bone marrow transplantation (ABMT) in childhood ALL after an isolated extramedullary (IE) relapse is controversial. Between December 1984 and November 1995, 52 children underwent ABMT because of an IE relapse. The data were stored in the AIEOP-BMT Registry. Thirty four children were transplanted in 2nd CR; eighteen > 2nd CR. The median duration of 1st CR was 24 (range 3-69) and 18 (range 3-59) months, respectively. The median interval from last CR to ABMT was 6 (range 1-28) and 3 (range 1-81) months, respectively. The 5 year EFS for patients transplanted in 2nd CR was 67.7%, while the 3 year EFS for patients in > 2nd CR was 16.7%. In conclusion, ABMT was an effective treatment in early IE relapse only if performed in 2nd CR.

Unrelated donor marrow transplantation: initial experience of the Italian bone marrow transplant group (GITMO).

From 1 September 1988 to 30 September 1993, a search for an unrelated donor (URD) was started for 633 Italian patients. Eighty-five of them (13%) were transplanted. Despite the introduction of more strict criteria for the selection of compatible donors, the percentage of patients who reached transplant increased significantly after December 1992. For patients who started a search before and after January 1993, respectively the probability of transplant by 8 and 16 months from search activation was 4 and 10%, compared to 22 and 37% (P = 0.0001). The average intervals between search activation and graft were 15 and 8 months respectively, for the first and second group (P = 0.0001). Data of 75 consecutive transplants performed up to March 1994 were analyzed. Actuarial 2-year survival was 15% for patients grafted before 1992 and 40% for those grafted after January 1992. In this latter period, survival of patients with malignant and non-malignant disorders was 32 and 67%, respectively. In univariate analysis, patients younger than 16 years (P = 0.01), patients grafted after 1992 (P = 0.01) and patients receiving the marrow from a 6-antigen matched donor (P = 0.01) showed a higher survival probability. Multivariate analysis did not show any difference, probably due to the low number of patients and to short follow-up. The adoption of stricter and more accurate HLA-matching criteria and the consequent reduction of deaths related to acute GVHD were the main reasons for the improvement of survival observed in patients grafted after 1992.

[Fungal infections in pediatric oncology]. / Infezioni fungine in oncologia pediatrica.

The clinical charts of cancer patients with documented fungal infections hospitalized at G. Gaslini Children's Hospital, Italy, from 1980 to 1990 were reviewed. Thirty-seven episodes developing in 37 patients were identified, based on microbiological and/or histological documentation. Patients' age ranged from 3 months to 18 years (median 7 years). Twenty patients were treated for hematological malignancy and 17 had solid tumor. Seven patients (3 with leukemia and 4 with solid tumours), developed mycosis after bone marrow transplantation procedure. A history of neutropenia in the month preceding the documentation of fungal infection was present in 76% of cases (28 of 37). However, only 16 of 28 (55%) of these patients were still neutropenic at time of diagnosis. In 40% of the cases the fungal infection developed as primary infection not preceded by any febrile and/or infectious episode. Fungemias without evident organ localization accounted for the 40% of episodes with a mortality rate of 20%. The other 22 cases (60%) were classified as invasive mycoses; 9 of these patients died (41%). Mortality was higher among patients with mold infection (5 of 7, 72%), than in those with yeast infection (7 of 29.24%). Molds infections and invasive mycoses were virtually absent in the first part of our period of observation (1980-84), but emerged in the second period (1985-90) when also the incidence rate of fungal disease increased (from 2.67/10,000 person/day to 5.93), probably in relation with extensive construction works and with the implementation of a bone marrow transplantation program.

[Sepsis related to a permanent central venous catheter in children with neoplastic disease: practical implications of a continuous surveillance of the etiology]. / Sepsi correlate a catetere venoso centrale a permanenza in bambini affetti da malattia neoplastica: implicazioni pratiche di una sorveglianza continua dell'eziologia.

Indwelling central venous catheter-related bacteremias are an important complication in patients with cancer. In general they are due to Staphylococcus aureus and Candida, while bacteremias caused by Gram-negatives are less common and often related to infusate contaminans. We describe a survey of etiological surveillance of Broviac catheter-related infections at G. Gaslini Children's Hospital of Genoa, Italy. In the period 1989-1992 an increase of Broviac catheter-related bacteremias due to Gram-negatives was demonstrated as compared with previous years (1985-1988). At home parental management was suspected as an important risk factor, since this complication was frequently due to infusate contaminants and no epidemic cluster or positive surveillance culture was observed in the Hospital. Therefore at home management was changed, especially regarding heparin storage. The subsequent, prospective follow-up from July 1993 to December 1995 showed a significant decrease in catheter-related bacteremias due to Gram-negatives (P = 0.003, chi-square test). In conclusion, a strict control on at home catheter management procedures must be maintained in order to reduce the risk of indwelling central venous catheter-related infections in children with cancer.

[Legal regulations to protect under-aged donors issued by E.U. Member Countries. Analysis of the present situation and proposals]. / Normative riguardanti la tutela del minore emanate nei Paesi membri dell'Unione Europea (UE). Analisi della situazione attuale e proposte operative.

Allogeneic bone marrow transplantation in the E.U. is a routine treatment which requires specific legal procedures to protect under-aged donors. The European Council (5/29/1978) decreed the guidelines concerning organ transplantation for the Member Countries. These guidelines included obtaining written consent from the donor or his/her guardian. The International Convention on children s rights (New York 11/20/1989, art. 12) stated that the minor has the right to give his/her opinion, which must be taken into consideration. Currently, though legal guidelines vary among Member Countries, all require the parents or guardian s written consent. In France, an ethics committee (L. 76-1181/1976) must inform the minor about the consequences of the procedure, respect his/her will and obtain consent. In Luxembourg, the Department of Health requires written consent as well as authorization by three experts, including two physicians. In Spain an ethics committee must obtain the minor s consent which is then approved by a government authority and counter-signed by a physician. In UK an N.H.S. directive (1st Aug. 1993) states that as of 16 years of age donors must give consent. In Germany minors over 14 are allowed to give consent. A legal guarantee is required when the recipient is a parent to avoid conflict of interest. In Belgium minors between 15 and 18 require witnessed written consent, counter-signed by the guardian and approved by a physician. Married donors below 21 need the consenting adult s approval. In Portugal verbal consent by the minor and the guardian is sufficient. In Denmark the guardian s written consent is needed. In Italy a law is being prepared to best protect minors. In conclusion it would be useful for the European Council to decree the detailed legal guidelines and require greater uniformity among the E.U. Countries.

[Caries in 6 to 12-year old children in 6 towns of Usl n. 16 of Modena]. / Studio sulla carie nei bambini di 6 e 12 anni in sei comuni dell'Usl n. 16 di Modena.

A "screening" done by the "Servizio Materno Infantile" of Modena relative to children from 6 to 12 years old during 1988-89 is described. The research is referred to 1454 children 6 years old attending the second year of the secondary school. For the evaluation of the level of the dental health have been used the Oms Index. The results are very comforting: the 54% of the 6 years old children have sound teeth, but from the dmft Index with a value of 1.6 comes out the trend not to cure the caries of the deciduous teeth. Very few are the cases of 6 years old children with caries of the permanent teeth. At 12 years the percentage of children with sound teeth is lower (34%), however analyzing the DMFT Index (1.9) appears a very high degree of attention towards the dental care.

CT of invasive pulmonary aspergillosis in children with cancer.

In treating cases of malignancy, the use of chemotherapy carries a high risk of lower respiratory tract infections, especially fungal pneumonopathy. This complication is a major cause of mortality and is often difficult to diagnose because of non-specific clinical or radiological changes, but the early recognition of invasive fungal disease is imperative. CT is an important non-invasive method for the detection and evaluation of opportunistic fungal infections. In these patients an improved survival rate can be achieved when early detection by CT leads to the prompt institution of high-dose antifungal therapy. We illustrate the spectrum of CT findings of invasive pulmonary aspergillosis encountered in children with cancer. These patients had previously been treated with high-dose chemotherapy with or without bone marrow rescue, and underwent radiological examinations because of clinical evidence of pneumonopathy. Representative cases demonstrate the clinical applications of CT in the evaluation and management of invasive fungal disease.

Unrelated donor marrow transplantation for chronic myelogenous leukaemia.

Between January 1989 and July 1995 the search for an unrelated donor (UD) was started for 379 consecutive Italian patients with Philadelphia positive (Ph+) chronic myelogenous leukaemia (CML). 89 (23%) were transplanted. The overall probability of transplant before and after December 1991 was 16% and 49%, respectively (P=0.0001), and average interval between search activation and graft was 23 months and 13 months, respectively (P=0.0001). Disease-free survival (DFS) following 60 consecutive transplants performed before February 1996 was 41.5% at 48 months and was 64% for patients grafted after January 1993. In univariate analysis, five variables had a favourable effect on DFS: year of bone marrow transplantation (BMT) after 1993 (P=0.0002), HLA-DRB1 donor/recipient (D/R) match (P=0.0006), total body irradiation (TBI) containing regimen (P=0.0006), graft-versus-host disease (GvHD) prophylaxis including 'early' cyclosporin before the transplant, and a marrow cell dose > 3 x 10(8)/kg of recipient body weight (P=0.04). Multivariate analysis confirmed that HLA identity (P=0.006), TBI-containing regimen (P=0.0001) and 'early cyclosporin' (P=0.04) were associated with higher DFS. Transplant-related mortality (TRM) was 67% in patients grafted before January 1993 and 30% in patients grafted subsequently (P=0.002). Multivariate analysis confirmed DRB1 identity (P=0.03) and TBI-containing regimen (P=0.0005) to be independent factors predictive of low TRM. This suggests that the outcome of patients transplanted from an HLA DRB1 matched donor, after a TBI-containing preparative regimen, is similar to results recently reported in patients transplanted from geno-identical siblings. These results indicate that the search should be initiated at diagnosis for patients < 45 years of age and UD BMT should be considered early in the disease course for those with an available DRB1-matched unrelated donor.