Hematologic improvement and response in elderly AML/RAEB patients treated with valproic acid and low-dose Ara-C.

The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has been shown to be active on acute myeloid leukemia (AML) and refractory anemia with excess of blasts (RAEB). Thirty-one elderly AML/RAEB patients (AML n=25; RAEB n=6) with a high rate of comorbidity were entered in a phase II study with low-dose cytarabine (Ara-C) and VPA. Fitness was evaluated by means of the Comprehensive Geriatric Assessment (CGA), including the Cumulative Illness Rating Scale (CIRS) score, the self-sufficiency scores of Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL). Eight patients obtained a lasting complete remission and 3 other patients obtained hematologic improvement for a total response rate of 35%. Five of 11 responding patients were relapsed or resistant after a previous treatment with Ara-C. Seven of 11 responding patients were assessed as frail at enrollment and/or had IADL impairment. Grades 3 and 4 toxicities were mainly hematological. Low-dose Ara-C and VPA is a relatively non-toxic combination with good therapeutic activity in elderly patients with AML/RAEB. This therapeutic approach represents an alternative treatment for patients who cannot undergo standard induction therapy.

Immunohistochemical expression of fatty acid synthase, Ki-67 and p53 in squamous cell carcinomas of the larynx.

Fatty acid synthase (FAS) is a recently discovered molecule involved in the energy supply to normal cells. FAS is overexpressed in neoplastic tissues because of their increased energy needs. We explored the immunohistochemical expression of FAS, Ki-67 and p53 in squamous cell carcinomas (SCC) of the larynx and their association with clinicopathological features and outcome. Specimens from 43 patients with SCC were evaluated. Statistical analysis revealed an association between poorly differentiated laryngeal carcinomas and FAS expression (p<0.005) and between FAS and Ki-67 overexpression (p<0.001). Finally, FAS expression was associated with overall survival (p<0.001). We suggest that FAS is a powerful prognostic indicator whose strength can be enhanced when it is evaluated together with clinicopathological data and Ki-67 expression.

[Monolateral adenopathy of the axilla due to sarcoid-type granulomata: idiopathic granulomatous disease or sarcoidosis? A case report]. / Linfoadenopatie ascellari monolaterali da granulomi di tipo sarcoidosico: malattia granulomatosa idiopatica o sarcoidosi? Caso clinico.

The presence of sarcoid-type granulomata in peripheral lymph nodes, with no evidence of other typical lesions, doesn't allow to diagnose sarcoidosis. In fact, sarcoidosis is a systemic disease and two or more organs must be affected to reach a definitive diagnosis. However this involvement could happen even several years later, thus making a correct diagnosis really difficult. In the absence of other organ involvement, an "idiopathic granulomatous disease" of peripheral lymph nodes is identified. Patients must anyway undergo a careful, long-term follow-up in order to detect clinical or radiologic variations that may confirm a diagnosis of sarcoidosis. After presenting a case-report of monolateral adenopathy of the axilla as an idiopathic granulomatous disease, the Authors review the international literature about sarcoidosis and its extra-pulmonar presentation, underlining the importance of considering sarcoidosis among possible diagnosis when peripheral adenopathies occur.

[A case of recurrent pharyngocele: treatment and literature review]. / Un caso di faringocele bilaterale recidivato come mediano e rioperato con successo.

Congenital or acquired pharyngocele is a rare disease characterized by a herniation of the pharyngeal mucosa through a "locus minoris resistentiae" of the lateral wall of the pharynx. Generally the pharyngocele does not present specific clinical signs or symptoms which makes it necessary to resort to radiological examination for the diagnosis. Our case is particular for primitive bilaterality and the single and median recurrence eight years later. After surgical excision the symptoms completely disappeared. The radiological examinations following surgery were negative.

[A case of lymphoepithelial cyst (branchial cyst) in an elderly patient: diagnosis differential, treatment and literature review]. / Un caso di cisti linfoepiteliale (branchiale) in un paziente anziano: diagnosi differenziale, trattamento e revisione della letteratura.

We present a case of lateral cervical cyst stressing the difficulties about the diagnosis. The international guidelines for the management of lateral neck cysts in the over 40s' age group are taken in consideration. Our case is a 74 years old male patient with a 6 month history of a cervical swelling. We consider this case rare for the age of patient and the absence of malignancy.

[Results of surgical treatment of varicocele in male infertility]. / Risultati del trattamento chirurgico del varicocele nella infertilità maschile.

To evaluate the results of surgical treatment of varicocele on infertile men, especially regarding sperm count, 245 patients, surgically treated from 1993 to 2003, were evaluated. Patients underwent to ligature and section of the pampiniform plexus, through the subinguinal approach and local anaesthesia. At the follow-up (3-6-12 months) an improvement of sperm count was relieved in 79.5% of patients and the incidence of complications and relapses was of 3.7% and 1.2%, respectively. The Authors stress the efficacy of surgical treatment of varicocele in male infertility and hold the subinguinal approach as an effective treatment, minimally invasive and low cost.

[Isolated agenesis of the gallbladder: case report]. / Agenesia della colecisti: caso clinico.

The gallbladder agenesis is a rare congenital abnormality which is frequently mistaken with cholecystolithiasis, regardless of the imaging modality used. The diagnosis is confirmed at laparoscopic surgery with intraoperative sonography and intraoperative cholangiography and postoperative MRI-cholangiography. Intraoperative cholangiography may be risky because the absence of normal anatomical structures and the impossibility of pulling on the gallbladder to dissect the triangle of Calot represents an increased risk of iatrogenic injury to biliary or portal structures. Therefore postoperative MRI-cholangiography seems to be a more suitable approach to confirm the diagnosis.

VEPEMB in elderly Hodgkin's lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study.

BACKGROUND: In advanced age the prognosis of Hodgkin's lymphoma (HL) is poor, but, as a consequence of the low incidence of HL in the elderly, prospective studies are lacking and the best treatment strategy is difficult to define. PATIENTS AND METHODS: One-hundred and five HL patients over 65 years of age were treated homogeneously with an original reduced-intensity regimen designed for HL in the elderly containing vinblastine, cyclophosphamide, procarbazine, etoposide, mitoxantrone and bleomycin (VEPEMB). Forty-eight early stage (IA-IIA) patients received three courses of VEPEMB followed by involved field irradiation. Fifty-seven advanced stage (IIB-IV) patients received six courses followed by radiotherapy limited to the areas of bulky disease. RESULTS: Mean age was 71 years (range 66-83). Co-morbidities were present in 39 patients (37%). A treatment plan modification for poor tolerance or toxicity was needed in 18 patients. Results were satisfactory, even if they were better in early rather than in advanced stage disease: complete response rate 98% versus 58% (P <0.01); 5-year failure-free survival 79% versus 34% (P <0.01). The results were affected by advanced stage, systemic symptoms and co-morbidity but they were not influenced by age itself. CONCLUSIONS: VEPEMB is an effective and low toxic regimen for HL in the elderly. Co-morbidity is a prognostic factor more important than age itself.

[Description of a case of giant adrenal myelolipoma and survey of the literature]. / Presentazione di un caso clinico di mielolipoma surrenalico gigante e revisione della letteratura.

Adrenal myelolipoma is a benign tumor affecting the adrenal gland. It is composed by adipose cells and myelopoietic cells present in each normal differentiating stage of the bone marrow. The neoplasia is often asymptomatic, sometimes leading to very large adrenal masses (more than 10 cm in diameter). These are often called "giant myelolipoma". A case is reported and a survey of the literature on this topic is made; the present knowledge of this disease as well as its diagnosis and treatment are discussed also.

[Milligan-Morgan hemorrhoidectomy with a radiofrequency scalpel]. / Emorroidectomia sec. Milligan-Morgan con bisturi a radiofrequenze.

BACKGROUND: Postoperative pain has always been the main adverse effect of surgical treatment for hemorrhoids. Therefore, surgical techniques evolved mainly to solve this problem and, secondly, postoperative bleeding, recurrences and stenosis. METHODS: Two homogeneous groups of 20 patients each were investigated. Both of them were affected by fourth grade hemorrhoidal prolapse and were homogeneous for age, sex and presentation symptoms. Patients previously treated for other proctologic diseases were excluded. A group was treated with standard Milligan-Morgan hemorrhoidectomy and the other with radiofrequency scissors. Every patient underwent a follow-up protocol based on outpatient visits at 15, 30, 45 postoperative days and 3, 6 and 12 months. RESULTS: The results show a substantial similarity between these techniques. However, radiofrequency scissors further improved the simplicity of the technique and the postoperative adverse effects. In particular, the procedure lasted 7 minutes less with radiofrequency scissors. Patients treated with the radiofrequency technique had their first postoperative evacuation 24 hours before the standard technique and reduced the mean postoperative hospital stay at 2.5 days (4.5 days in the standard group). The incidence of postoperative pain was reduced in patients treated with radiofrequency scalpel and the follow-up controls in both groups didn't show any complication as stenosis or incontinence. CONCLUSIONS: The radiofrequency-performed Milligan-Morgan hemorrhoidectomy is a valuable technique that improves the classical difficulties in execution, reducing the length of hospital stay and the incidence of postoperative pain or other complications.

Allogeneic bone marrow transplantation (BMT) for adults with acute lymphoblastic leukemia (ALL): predictive role of minimal residual disease monitoring on relapse.

We developed a PCR-based method to monitor clonogenic IgH VDJ rearrangement as a possible predictor of relapse in patients with acute B-ALL after allogeneic bone marrow transplantation (BMT). We studied 23 patients at diagnosis, before and after BMT. At the time of BMT, 13 patients were in first complete remission, eight in second complete remission and two in relapse. Four patients were PCR negative before BMT and remained PCR negative also after BMT (-/- pattern). They are still in remission after a median follow-up of 41 months. Nineteen patients were MRD-positive before BMT: three were PCR negative at first determination after BMT (+/- pattern) and maintain remission. Sixteen patients were PCR-positive at first determination after BMT (+/+ pattern): five became PCR negative (+/+/- pattern) (four with chronic graft-versus-host disease (GVHD) and two after donor lymphocyte infusions (DLI)). Nine patients remained PCR-positive (+/+/+ pattern) (four remain in remission, and six relapsed); two patients died before transplant. In conclusion, PCR negative patients before BMT remained negative post-BMT; many pre-BMT positive patients had initial MRD positivity after BMT: 37% of them achieved a molecular remission with cGVHD or DLI.

Molecular analysis of patients with relapsed or refractory intermediate-high grade non-Hodgkin's lymphoma with bone marrow infiltration undergoing peripheral blood progenitor cell transplantation.

BACKGROUND AND OBJECTIVES: IgH gene rearrangement studies with a polymerase chain reaction (PCR) technique can detect the persistence of clonal cells at molecular level during the remission phase. This persistence of clonal cells can be used to establish the relationship between minimal residual disease (MRD) and clinical outcome. We have developed a three-step single strand conformational polymorphism PCR strategy which is able to detect clonal B lymphoid cells at a frequency as low as 1 clonal cell in 10(6) normal cells. DESIGN AND METHODS: Twenty patients with intermediate or high-grade B non-Hodgkin's lymphoma (NHL) were evaluated. Patients were pre-treated with a median of two (range 1-4) conventional chemotherapy lines before high-dose cyclophosphamide (HDCY). All patients had their bone marrow (BM) involved by disease (median 10%; range 5-50%). Nineteen patients were offered high-dose therapy followed by peripheral blood progenitor cells (PBPC) autografting. RESULTS: MRD analysis was performed for each patient at the end of conventional chemotherapy and every three months after high dose therapy. All these patients achieved complete response (CR) after high dose therapy (HDT). Six patients relapsed after a median time of 24.5 months. All the studied apheresis samples were positive at the molecular analysis. All 6 patients still positive at the molecular analysis after PBPC autografting relapsed. The remaining 13 patients who were negative maintained CR. INTERPRETATION AND CONCLUSIONS: Whereas the detection of clonal cells in the apheresis samples did not predict an unfavorable outcome, the disappearance of the clonal rearranged band from the BM sample after HDT proved to be a favorable prognostic factor and was associated with long-lasting disease-free status

Detection of minimal residual disease in B-lymphoproliferative disorders: a three step SSCP-PCR method.

The most recent therapeutic approaches can improve the outcome of B-cell neoplasia. By PCR analysis we amplify tumor specific DNA sequences of clonal IgH rearrangement from a limited number of malignant cells against a background of normal B cells. Recently described PCR based techniques for tracking minimal residual disease (MRD) in B lymphoproliferative disorders have given promising but discordant results, with significant variations in the sensitivity and specificity of the procedures. We have developed a three step single strand conformational polymorphism polymerase chain reaction (SSCP-PCR) strategy which is able to detect clonal malignant cells in B lymphoproliferative disorders at a frequency as low as 1 in 10(6) cells. Since this method is simple, rapid, reliable and as specific as ASO-PCR, it could be especially useful in monitoring patients affected by B lymphoproliferative disorders in complete haematological and immunophenotypic remission.

GM-CSF, ARA-C, VP-16 and idarubicin (GM-IVA), a short, and effective induction treatment for de novo AML, suitable for the elderly.

GM-IVA is a short and effective induction therapy of non M3 de novo AML including GM-CSF (300 mcg 12 hrs before starting therapy), Ara-C (250 mg/sqm c.i. x 3 days), VP16 (100 mg/sqm x 3 days) and idarubicin (12 mg/sqm x 3 days); it was followed by a fludarabine containing salvage protocol (FLANG). Patients <60 years of age achieving CR received 2 courses of FLANG and autologous or allogeneic BMT when possible. Patients >60 years of age in CR received a second course of GM-IVA. Twenty-one consecutive patients (mean age 64, range 29-85) entered the study. Three patients (14%) died during induction therapy. After one course of GM-IVA, CR was achieved in 12 patients (57%). Two further patients were salvaged with FLANG therapy so that the final CR rate was 14/21 (67%). In elderly patients the final CR rate (62%) is noteworthy, considering that 6 patients were >70 years of age and 3 were >80. All three patients >80 achieved CR (lasting 5 to 7 months). The median time of granulocyte and platelet recovery was 15 days. Our scheme was well tolerated. In the group of elderly patients 3 out of 14 died during induction (21%) and 4 life-threatening infections were observed (28%). The short duration of cytotoxic therapy and perhaps the use of G-CSF contributed to a reduction of the hospitalization period (median of 22 days), thus providing major savings on induction costs and allowing for better utilization of beds as well as significantly improving patients' quality of life.

First line Fludarabine treatment of symptomatic chronic lymphoproliferative diseases: clinical results and molecular analysis of minimal residual disease.

Fludarabine (25 mg/m2 for 5 d, every 4 wk, for 6 courses) was administered as first line therapy in 32 symptomatic chronic lymphoproliferative diseases. All CLL patients achieved at least partial response (5 CR, 2 nPR, 9 PR) but 44% of patients relapsed. In LG-NHLs response and relapse rate were similar. Haematological toxicity was low. VDJ rearrangement PCR analysis was performed on marrow samples at diagnosis and at the time of response evaluation. In the 3 patients who underwent high dose therapy with peripheral blood progenitor cell rescue analysis was also performed on apheresis samples and on marrow samples at the end of the procedure. Clonal VDJ rearrangement was always evident after Fludarabine therapy even in those patients who achieved histological and immunophenotypic complete remission, whereas it disappeared in 2 of 3 patients who underwent HDT. Our data confirm that Fludarabine monotherapy can reduce the neoplastic mass to a subclinical level and suggest the possibility that high dose therapy might produce true complete remission.

Long-lasting effect of cyclosporin-A on anemia associated with idiopathic myelofibrosis.

Some reports suggest that immunologic mechanisms may play a role in the pathogenesis of anemia in idiopathic myelofibrosis (IMF). Herein we report the case of a transfusion dependent IMF patient with psoriasis in whom cyclosporin-A (CyA) treatment for skin lesions (200 mg/day) was associated with long-lasting correction of anemia. After 2 months of CyA therapy the patient's Hb level increased and he became transfusion free in 4 months. After 12 months immunosuppressive therapy was discontinued due to renal toxicity, yet the Hb level remained stable for an additional 12 months. The patient is currently being administered CyA at a reduced dosage because of mild renal impairment along with transfusional support consisting of a median of 2 red cell units/month. Altogether the patient received no transfusional support for 36 months. This case, as well as other reports, suggests that the issue of immunosuppressive treatment in IMF anemia deserves further investigation.

Multiple myeloma in the elderly: clinical features and response to treatment in 113 patients.

BACKGROUND: Considering the conflicting results of the few reports on geriatric MM patients and the increasing relevance of the problem, we analyzed a series of 113 patients over 64 years of age treated with conventional chemotherapy. PATIENTS AND METHODS: The median age was 71 (range 65-92). Stage IA, IIA, IIIA and IIIB patients numbered 28, 33, 45 and 7, respectively. The M component was IgG in 73 patients (65%), IgA in 30 (26%), IgD in 3 (3%), light chain in 5 (4%); no monoclonal component was detected in 2 (2%) cases. Sixty-three patients showed symptomatic skeletal disease. Melphalan/prednisone (MP) was the first-line treatment in 84 patients (74%). Patients were grouped according to age (> 64 < or = 74; > or = 75) in order to carry out analysis. RESULTS: Seventy-eight cases (69%) showed a sizable reduction in the tumor mass; objective and partial response was achieved in 57 (50%) and 21 (19%) patients, respectively. Patients with stage I-II disease fared significantly better than stage III patients (median survival: 70 vs 38 months; p = 0.017). Response to first-line treatment correlated with overall survival; patients with responsive or refractory disease had median survival rates of 64 and 20 months, respectively (p = 0.0001). CONCLUSIONS: Neither patients above nor below 75 years of age showed any difference in presentation features or in response to treatment. These results suggest that advanced age should not be considered a major obstacle to active treatment.