Neurofibromatosis type 2 discordance in monozygous twins.

Neurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in the NF2 gene. The pathogenic variant is either inherited or obtained by de novo mutation, characterised by the presence of schwannomas, meningiomas and ependymomas. Here we report the presence of NF2 in one twin, with bilateral vestibular schwannomas and a pathogenic variant of the NF2 gene identified in both tumour and lymphocytes, while his monozygous brother remains asymptomatic. Imaging of the unaffected twin showed no tumour load and genetic testing via Sanger sequencing and Amplification Refractory Mutation System assay demonstrated low levels of expression of the NF2 variant in lymphocytes. Further testing on non-haemopoietic tissue showed little expression or absence of the pathogenic variant. Given there is no family history and the low level of the variant, we assume the pathogenic variant is a de novo mutation during embryogenesis. De novo mutations have been described as occurring at three possible time points in the creation of monozygous twins with different genetic make-up; prior to the twinning event, as a cause of the event, or after the twinning event. Of these options, we hypothesise that the discordance in the expression of the NF2 variant between these twins is likely due to a mutational event that occurred as a result of either of the latter two possibilities, between which we cannot determine. The pathogenic variant in lymphocytes was likely transferred between the twins through a shared blood supply in utero, and the non-haemopoietic samples that showed low levels of expression, were likely due to the presence of lymphocytic cells. Therefore, we have a discordance between monozygous twins at the NF2 gene.

Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

AIM: This retrospective multi-institutional study addresses the role of surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of multicystic peritoneal mesothelioma (MCPM). MCPM is an uncommon tumour with uncertain malignant potential and no current standard therapy. Additionally, poorly defined pathological and biological features of this disease were investigated. METHODS: Twelve patients with MCPM underwent 14 procedures of cytoreduction and HIPEC in two Italian referral centres. Nine patients had recurrent disease after previous debulking (one operation in six patients, two in two, four in one). Biological markers related to mesothelioma origin and clinical features were assessed by immunohistochemical studies. RESULTS: Median follow-up was 64 months (range 5-148). Optimal cytoreduction (residual tumour nodules ≤2.5 mm) was performed in all the procedures. One grade IV postoperative complication (NCI/CTCAE v.3.0) and no operative death occurred. All the patients are presently alive with no evidence of disease, including two patients who underwent the procedure twice, due to locoregional disease recurrence. Five- and ten-year progression-free survival was 90% and 72%, accounting for a. statistically significant difference (P = 0.0001) with progression-free survival following previous debulking surgery (median 11 months; range 2-31). All cases showed low proliferative activity assessed by mitotic rate and Ki-67 expression. CONCLUSIONS: MCPM is a borderline tumour with a high propensity to local-regional recurrence. Definitive tumour eradication by means of cytoreduction and HIPEC seems more effective than debulking surgery in preventing disease relapse. Low mitotic rate and poor Ki-67 expression might be related to the peculiar behaviour of MCMP.

Splenic lymphangiomatosis associated with skeletal involvement (Gorham's disease): a new case and review of literature.

Lymphangiomatosis is a well-recognized congenital benign tumour, frequently seen in infancy and childhood, characterized by the presence of multiple lymphangiomas. Diffuse lymphangiomatosis also involving bony tissue is called Gorham's disease. This condition generally affects somatic soft tissue, where lymphatics are normally found. A predilection of this affection for bone, thoracic and neck involvement is well known, while involvement of abdominal viscera is very unusual. In bone this non malignant proliferation of lymphatic channels results in destruction and resorption of the osseous matrix. We report on a child in whom lymphangiomatosis involved both the bone and the spleen. A review of 166 cases is also reported.

A novel technique for rectocele repair in elderly women.

We have developed a transvaginal technique for rectocele repair which we believe to be particularly suitable for older woman. A transverse incision was made in the mucocutaneous border of the vaginal introitus. The rectal wall was separated from the rectovaginal septum. The vaginal wall was divided in the middle. The first flap was sewn to the second and this onto the first. This intervention permits the contemporary correction of other pathologies frequently found in older women, such as cystocele and prolapse of the uterus. Twenty-two elderly women underwent operations using this technique; the mean follow-up period was 48 months (range, 24-84 months). The need to assist evacuation digitally disappeared in all patients.

Experimental investigation of various vegetable fibers as sorbent materials for oil spills.

Oil spills are a global concern due to their environmental and economical impact. Various commercial systems have been developed to control these spills, including the use of fibers as sorbents. This research investigates the use of various vegetable fibers, namely mixed leaves residues, mixed sawdust, sisal (Agave sisalana), coir fiber (Cocos nucifera), sponge-gourd (Luffa cylindrica) and silk-floss as sorbent materials of crude oil. Sorption tests with crude oil were conducted in deionized and marine water media, with and without agitation. Water uptake by the fibers was investigated by tests in dry conditions and distillation of the impregnated sorbent. The silk-floss fiber showed a very high degree of hydrophobicity and oil sorption capacity of approximately 85goil/g sorbent (in 24hours). Specific gravity measurements and buoyancy tests were also used to evaluate the suitability of these fibers for the intended application.

Surgical approach to cervical lymph node metastasis in differentiated thyroid cancer.

BACKGROUND: Precautionary locoregional lymph node dissection in thyroid carcinomas for diagnostic and/or staging purposes is useless both in differentiated (papillary and follicular) and undifferentiated forms. It is only indicated in medullary carcinomas because of their frequent spread to regional lymph nodes. The objective of lymphadenectomy is to contain tumor spread; however, the procedure may be associated with intraoperative complications and postoperative sequelae. In order to improve the therapeutic management of patients with thyroid carcinoma, diagnostic scintigraphy with 201T1 or 99mTc-sestamibi is used in the advanced and undifferentiated forms of this tumor. METHODS: We have treated a woman submitted three years previously to total thyroidectomy for papillary carcinoma (pT3) without subsequent radiometabolic treatment. On physical examination we noted a swelling on the left side of the neck. The lesion was confirmed by ultrasonography, CT scan, and scintigraphic examination with 99mTc-sestamibi 24 hours before planned lymphadenectomy. During the surgical procedure we performed radiodetection to localize metastatic lesions. RESULTS: Intraoperative radiodetection may help to identify residual disease, which is often difficult to trace in the presence of post-surgical fibrosis. In our patient, histological examination of the removed tissue specimens demonstrated that intraoperative radiolocalization had been highly accurate. The eradication of residual disease was confirmed by scintigraphic follow-up after 12 months. DISCUSSION AND CONCLUSIONS: Scintigraphy with 99mTc-sestamibi has been proposed as a means to localize metastatic spread and possible residual disease after a supposedly radical thyroidectomy. Surgical eradication of all residual tumor guarantees the best disease control without having to resort to radiometabolic therapy. This approach will reduce the incidence of iatrogenic comorbidity and consequently improve the patients' quality of life.

Assessment of the value of treatment with granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a randomized clinical trial.

The present trial was designed to test the effects of G-CSF on the duration of the second phase of induction chemotherapy in children with newly diagnosed acute lymphoblastic leukemia (ALL). A total of 32 patients were assigned randomly to a group that received (14 patients; group A) or a group that did not receive (18 patients; group B) G-CSF (10 g/kg/day subcutaneously and daily) throughout of the second phase of induction therapy. One of 14 (7.1%) patients in group A and 2 of 18 (11.1%) patients in group B completed the course of chemotherapy within the planned time. The median length of this phase was 37 days (range, 29 to 65; mean, 40; SD, 8.6) for patients in group A and 36 days (range, from 29 to 55; mean, 38; SD, 7.4) for those in group B, and the difference was not statistically significant. The number of days during which patients had granulocyte counts of less than 2 x 10(9)/l, the number of febrile episodes of unknown origin, the number of bacterial and fungal infections and the number of days of hospitalization did not differ in a statistically significant manner between the two groups. Our data suggest that G-CSF supportive therapy may be unnecessary in children with neutropenia of short duration, for whom the risk of infection is low.

Value of antigen and antibody detection in the serological diagnosis of invasive aspergillosis in patients with hematological malignancies.

In a study to determine the value of antigen and antibody detection in the serological diagnosis of invasive aspergillosis in patients with hematological malignancies, 436 sequential serum samples from 79 neutropenic patients were tested. Circulating galactomannan antigen was detected with a latex agglutination method (Pastorex Aspergillus) and antibody to Aspergillus fumigatus with an immunodiffusion test on agar gel. Among the 79 patients 18 cases of invasive aspergillosis were detected (4 proven, 6 highly probable, 3 probable, 5 suspected). Antigen was detected in 7 of these 18 patients. The sensitivity of the antigen test was 38.8% and the specificity 95%. The antibody test showed 55.5% sensitivity and 100% specificity. In this study the antigen test was less sensitive than previously reported but highly specific and might serve as a supplementary diagnostic test.

[Acute lymphoblastic leukemia in children. Results of treatment in Sicily 1987-1992]. / Leucémie aiguë lymphoblastique de l'enfant. Résultats du traitement en Sicile entre 1987 et 1992.

OBJECTIVES: For several years, children in Sicily with acute lymphoblastic leukaemia have been treated locally at the University of Catania. We compared the results of locally treated children with the results obtained at other centres. METHODS: The diagnosis of acute lymphoblastic leukaemia (ALL) was made in 78 children in the haematology and oncology division of the University of Catania, Sicily, From January 1987 to December 1992. Patients diagnosed before December 1990 were treated with the protocol ALL 87 including prednisone, vincristine, daunorubicine, L-asparaginase and intrathecal methotrexate. Total duration of treatment was 25-26 months. For patients diagnosed after December 1990, the protocol 90-91 used the same drugs for induction and three intrathecal drugs (methotrexate, cytarabine and prednisone) as well as cyclophosphamide to prolong induction in intermediary risk patients. Only high risk patients received cerebral irradiation. Total duration of treatment was 2 years. Full follow-up data were available for 76 patients. RESULTS: Survival rate without relapse was 66% and the 5-year survival rate was 82.7%. These results were comparable with those published by other international groups. In addition, particular attention was given to psychological support to decrease the deleterious effects of both the disease and the treatment protocols. CONCLUSION: These results demonstrate that ALL children can be cared for locally in Sicily without risking poorer outcome. It would be preferable to treat these children as near as possible to their area of residence in order to diminish the psychological trauma resulting from long-term hospitalization far from their family.

6-Mercaptopurine cumulative dose: a critical factor of maintenance therapy in average risk childhood acute lymphoblastic leukemia.

A multivariate survival analysis including gender, age, log white blood cell (WBC) count, liver and spleen size at diagnosis, mean log WBC count during maintenance therapy, and the prescribed cumulative doses of 6-mercaptopurine (6-MP), methotrexate (MTX), vincristine (VCR), and prednisone (PDN) during maintenance therapy was performed on 53 children with average-risk acute lymphoblastic leukemia (ALL). The 6-MP cumulative dose prescribed during maintenance therapy resulted in the most important statistically significant independent prognostic factor. Patients who received less than the median cumulative dose of 6-MP (86% of planned protocol dose) fared significantly worse than the other patients, regardless of WBC count at diagnosis, gender, age, and other factors studied. Therefore, 6-MP cumulative dose during maintenance therapy may be the critical factor for effective maintenance therapy in childhood ALL.

Primary myelofibrosis: a detailed statistical analysis of the clinicopathological variables influencing survival.

In the present study we analyzed the prognostic significance of several clinical, hematological, and histological parameters recorded at diagnosis in a consecutive series of 72 patients with primary myelofibrosis (PMF). Univariate analysis showed that the most significant indicators of poor survival were the following: age greater than 60, splenomegaly, anemia (hemoglobin > 10 g/dl), leukopenia (WBC < 4 x 10(9)/l or leukocytosis > 14 x 10(9)/l), and any of these histological features: adipose tissue and megakaryocyte reduction, prominent osteoblastic rims along the trabecular bone, presence of peritrabecular megakaryocytes (Mk), absence of normal or giant Mk. The multivariate analysis showed that only the level of hemoglobin and the presence of both normal Mk and fever independently influenced the prognosis. These parameters were used to set up a prognostic scoring system, allowing a feasible prognosis to be made for each patient at the time of diagnosis and identifying those patients in urgent need of new therapeutic approaches.

Incidence and morbidity of infection by hepatitis C virus in children with acute lymphoblastic leukaemia.

A group of 90 patients with acute lymphoblastic leukaemia (ALL) in first continuous complete remission (CCR), admitted in our hospital between January 1986 and September 1992, were tested for the presence of antibodies against hepatitis C virus (HCV), antibodies against hepatitis B virus and antibodies against HIV-1 during maintenance therapy or thereafter. They were compared with a group of 71 children with other malignancies in first CCR who had been diagnosed consecutively from January 1986 to September 1992. No patient with ALL or any other malignancy was found to be positive for hepatitis B surface antigen or HIV-1. HCV-specific antibodies were detected in 28 out of 87 children (32.1%) with ALL and in 4 out of 44 patients (9%) with malignancies other than ALL who had received at least one transfusion of blood or platelets (P < 0.01). HCV-specific antibodies were also detected in one out of three untransfused children with ALL but in none of the untransfused children with malignancies other than ALL. HCV-specific seropositivity influenced the management of children with ALL during maintenance therapy. In fact, as a result of abnormal liver function tests, maintenance therapy had to be suspended significantly more often in the case of HCV-seropositive patients with ALL than in HCV-seronegative ones. Despite the high morbidity during maintenance therapy, chronic liver disease (CLD) was uncommon in both groups: five children with ALL (17.2% of HCV-seropositive children) and one child with a malignancy other than ALL (25%) had CLD.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidencia de los distintos agentes etiológicos de micosis superficiales / [Incidence of various etiologic agents of superficial mycosis]

In a retrospective review of laboratory records at the Department of Mycology, National Institute of Microbiology [quot ]Dr. Carlos G. Malbrán[quot ], during the period June 1989-July 1991, 1225 putatively immunocompetent cases of superficial mycoses were identified. Ninety five percent of these patients were adults and 5

children. Among the total cases, dermatomycoses were caused, 67.6

by Malassezia furfur. and 0.5

by other fungi, as proven by the isolation of the etiological agents. (Figure 1, Table 2). Among the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes greatly predominated accounting for 66.6

of the isolates, respectively, whereas Microsporum canis (8.0

) and Microsporum gypseum (0.3

) were found with less frequency (Figure 2). Nails (47

) were the most common source of isolates in adults, followed by feet (28

) and hands (2

) (Table 1). Regarding the relative efficiency of the diagnostic methods, the analyses of laboratory results evidenced that, 98

of the cases with clinical findings compatible with mycoses and 76

of the cases with positive cultures (Table 1) were identified by microscopic observation.

[Polyneuropathies associated with lymphoplasmacytic dyscrasias: the clinical and instrumental characteristics of a 38-patient case load]. / Polineuropatie associate a discrasie linfoplasmacellulari: caratteristiche cliniche e strumentali di una casistica di 38 pazienti.

A varying percentage from 40 to 60% of patients having lymphoplasmacytic dyscrasias with a monoclonal component shows a clinical or subclinical polyneuropathy. From a different viewpoint, a monoclonal gammopathy has been detected in 10% of patients effected by chronic idiopathic polyneuropathy. A case study of 38 patients with lymphoplasmacytic dyscrasia subjected to clinical, immunohematological and electrophysiological examination revealed a high prevalence of polyneuropathy (84%), mainly axonal (72%) and often subclinical. The neuropathy was evenly distributed between patients having malignant and benign lymphoplasmacytic dyscrasias. No statistically significant correlation was found between the presence of neuropathy and the main clinical and immunohematological data. This supports the concept that the pathogenesis of polyneuropathy associated with lymphoplasmacytic dyscrasias may be multifactorial. Nor can it be ruled out that the paraprotein may in fact be secondary to the polyneuropathy or sometimes a simple coincidence.

Phosphatase isoenzymes as bone metastasis markers in prostatic carcinoma.

Bone alkaline phosphatase (b-ALP) and tartrate resistant acid phosphatase (tr-ACP) are markers of the activity of osteoblasts and osteoclasts, respectively. We have already shown that the serum activity of these isoenzymes was elevated in breast cancer patients with bone metastasis (BM); we show here that the serum activity of b-ALP and tr-ACP were also elevated in prostate cancer patients with BM. Specificity and sensitivity of b-ALP for BM were 0.90 and 0.75, respectively; and for tr-ACP, 0.60 and 0.60, respectively. The accuracy of b-ALP as a BM marker was higher than the accuracy of usual markers of prostatic carcinoma (tartrate labile ACP [tl-ACP], prostatic acid phosphatase [PAP] and prostate specific antigen [PSA]). The highest value predictive of a positive bone scan was obtained with b-ALP (0.88); this increased to 0.97 when b-ALP was coupled with PAP.