Tiziana Toffolutti

Safety and efficacy of caspofungin and liposomal amphotericin B, followed by voriconazole in young patients affected by refractory invasive mycosis

Abstract:  Objective: Data on the use of combination of liposomal amphotericin B and caspofungin followed by voriconazole, as maintenance or further rescue treatment, in 10 patients with invasive mycosis are reported. Material and methods: The diagnoses were acute leukemia (7), myelodysplastic syndrome (1) and Hodgkins lymphoma (1). All patients developed an invasive mycosis (proven, 3; probable, 6; and possible, 1) refractory to first‐line antifungal treatment (liposomal amphotericin B in all patients except one who received fluconazole). Results: Rescue therapy with a combination of caspofungin and liposomal amphotericin B was well tolerated, hypokalemia, and thrombophlebitis being the most common side‐effects. Combination therapy was administered for a median of 17 d, range 6–40. Among the nine patients with proven or probable mycosis, one was not evaluated because of early death caused by massive hemoptysis whilst in the remaining eight patients, the response was classified as complete, stable and failure in four, three, and one patients, respectively. Complete response was also observed in patient with possible mycosis. Eight of nine patients received voriconazole for a median of 75 d, range 42–194. Voriconazole was well tolerated although some drug interactions were observed during treatment with methotrexate and digoxin. After a median follow‐up of 125 d, nine of 10 patients are alive. Overall, a favorable response to antifungal treatment (including the case of possible mycosis) was obtained in eight of 10 patients. Conclusion: These data suggest that medical antifungal treatment may be intensified in severely ill patients without significantly compromising patient safety. The combination of synergistic antifungal drugs as well as their sequential use warrants further investigation by a larger randomized controlled study.

TESTICULAR CYSTIC DYSPLASIA: EVALUATION OF 3 NEW CASES TREATED WITHOUT SURGERY

PURPOSE We describe 3 cases of testicular cystic dysplasia that were diagnosed only by sonography to avoid an invasive approach. MATERIALS AND METHODS Three patients 5, 8 and 12 years old, respectively, had increased testicular volume and/or intermittent pain. Sonographic examination of the testis by high frequency (7.5 mHz.) probes showed the typical onset of testicular cystic dysplasia, characterized by several small focal or diffuse intraparenchymal cystic formations. RESULTS Biopsy or orchiectomy was not considered. At 16, 18 and 24 months of followup, respectively, testicular pain was absent in our 3 cases and sonographic findings were unchanged. CONCLUSIONS Clinical and sonographic followup is considered sufficient to evaluate possible changes in the clinical course of this pathological condition which, although benign, still remains to be defined.

A case of resistant pediatric histiocytic sarcoma successfully treated with chemo-radiotherapy and autologous peripheral blood stem cell transplant

The term ‘mono-histiocytic system’ groups a wide spectrum of cells which probably derive from a common hematopoietic progenitor in the bone marrow (BM). These cells can be divided into two main categories: antigen presenting cells (APCs) and antigen processing cells. APCs include Langerhans cells, follicular dendritic cells, and interdigitating cells, whereas antigen processing cells consist of tissue macrophages and monocytes. Each of these cell types can undergo malignant transformation, thus originating localized or disseminated cancers [1]. Morphologic identification of the different cell types can be difficult; however, they can be recognized with the help of immunohistochemical analysis, since each cell type expresses a lineage-specific pattern of antigens that can be detected by combinations of monoclonal antibodies. True histiocytic sarcoma (HS) is a rare malignancy composed of cells that morphologically and immunohistochemically resemble mature tissue histiocytes. HS shows CD68 and lysozyme expression, whereas interdigitating reticulum cell sarcomas and follicular dendritic cell sarcomas are, respectively, characterized by strong expression of S100 protein and CD21/CD35. Furthermore, the main feature of Langerhans cell malignancies is positivity for both S100 and CD1a [2]. HS has been misdiagnosed in the past when it was often confused with non-Hodgkin lymphomas, particularly with anaplastic large cell lymphoma [3,4]. It can originate at different sites, most commonly spleen, liver, lymph nodes, gastrointestinal (GI) tract, and skin, and can present as localized or disseminated disease. The clinical course is usually aggressive and there is no consensus on the prognostic factors and the optimal treatment approach, although lymphoma-based protocols are often used [5,6]. We report a case of successfully treated HS of childhood with peculiar localization in the rhinopharynx and a review of the recent literature on the disease. A 9-year-old white male was admitted to our center with blurred vision and frontal headache, initiated 6 months earlier. He was previously diagnosed with sinusitis at another hospital, based on an ear–nose–throat (ENT) evaluation and X-ray examination of the nasal sinuses, and was treated with local and systemic antimicrobial therapy. A few months later, due to persistence of the symptoms, he underwent a second ENT evaluation followed by adenoidal tissue biopsy. Histological examination showed widespread infiltration of neoplastic cells with histioid appearance. The histioid differentiation was confirmed by immunohistochemical analysis [Figure 1(A)], which demonstrated positivity for CD45, CD68, CD163, and focally for lysozyme. S100 protein was only focally expressed whilst CD1a was negative. Other markers of follicular dendritic cell differentiation (CD21, CD23, CD35), as well as

Management of unresectable solid papillary cystic tumor of the pancreas. A case report and literature review

Pancreatic solid papillary cystic tumor is a rare neoplasm with an excellent prognosis if surgical excision is complete. We report on a case and review 47 more cases extracted from the published literature to assess the treatment options when solid papillary cystic tumor is considered unresectable. Chemotherapy and radiotherapy were beneficial in a limited number of patients, but therapeutic decisions must be made bearing in mind that patients may be long-term survivors without any treatment because of the tumors slow growth.

Multiple synchronous tumors in a child with Fanconi anemia.

Fanconi anemia (FA) is an autosomal recessive inherited syndrome characterized by congenital abnormalities, aplastic anemia, and a high likelihood of developing cancer. We describe a child who presented with 2 synchronous solid tumors (Wilms tumor and neuroblastoma), later found to have FA, who developed severe toxicity and died after a first cycle of chemotherapy. Our experience emphasizes that a predisposing genetic condition should be sought in cases of multiple tumors and that managing FA patients with cancer can be particularly difficult.

Combination antifungal therapy and surgery for the treatment of invasive pulmonary aspergillosis after hematopoietic stem cell transplantation

An 8-year old boy, affected by severe aplastic anemia, developed a probable pulmonary invasive aspergillosis (IA) early after a second unrelated allogeneic hematopoietic stem cell transplant (HSCT). He was treated promptly with the combination of liposomal amphotericin B and caspofungin. Despite the initial stabilization, the patient deteriorated and the antifungal therapy was switched to voriconazole and caspofungin. The patient gradually improved and was discharged home on day +29 post-HSCT on oral voriconazole. On day +119, a sudden episode of hemoptysis occurred and a right superior lobectomy was decided to remove the residual aspergilloma. The patient is now alive and well more than 24 months from HSCT. This case demonstrated that antifungal combination therapy and surgery are valid options to cure pulmonary IA even in patients at high-risk and severely immunosuppressed.

Successful treatment of disseminated fusariosis in a child with acute myelogenous leukaemia with medical and surgical approach

We report a case of disseminated fusariosis in an 8‐year‐old boy with acute myelogenous leukaemia that occurred whilst the patient was severely neutropenic after high‐dose chemotherapy. Lung involvement was associated with recurrent typical skin lesions. Despite a significant clinical and radiological improvement with voriconazole‐based antifungal therapy, granulocyte transfusions (GTXs) and surgical excision of residual lesions were necessary to achieve a complete response before the patient proceeded to allogeneic stem‐cell transplantation from an alternative donor. Voriconazole was continued for 6 months after transplant as secondary prophylaxis. After 15 months of follow‐up, the patient is alive and well, and in complete remission of his underlying disease. Triazoles have the potential for improving the cure rate of Fusarium infections but both surgery and shortening the duration of neutropenia by GTXs are important factors in optimising the results.