Bone disorders in patients with chronic liver disease awaiting liver transplantation.

BACKGROUND: An important complication of chronic liver disease is osteodystrophy, which includes osteoporosis and the much rarer osteomalacia. Both conditions are associated with significant morbidity through fractures resulting in pain, deformity, and immobility. Liver transplantation may further deteriorate bone metabolism. The aim of the present study was to investigate the frequency and severity of hepatic osteodystrophy among patients with liver cirrhosis who were referred for liver transplantation. We also evaluated modifications in bone metabolism after liver transplantation. MATERIALS AND METHODS: We recruited 35 consecutive patients with chronic liver disease who were undergoing assessment for transplantation over a 1-year period. Bone mass in the total skeleton and proximal hip was evaluated using a dual-energy X-ray absorptiometry device (Lunar Prodigy Advance, GE Healthcare, USA). According to World Health Organization recommendations, osteoporosis was defined as a T score < -2.5 and osteopenia as T score between -1 and -2.5. RESULTS: We enrolled in the study 35 patients, including 8 females and 27 males of overall mean age of 57 +/- 7, who showed a viral etiology (57%) or alcohol etiology (28%), Child-Pugh 8.7 +/- 2.3. The overall prevalence of osteodystrophy was 40% (26% osteopenia and 14% osteoporosis). No difference was evident according to gender, severity of liver disease (Child-Pugh, Model for End-stage Liver Disease), or origin of liver disease. A subgroup of 10 transplanted patients reached 3-month follow-up, showing total body T score with a significant decrease after 3 months while femoral T scores tended to decrease insignificantly. CONCLUSIONS: This study revealed a high prevalence of low bone mineral density among cirrhotic patients before liver transplantation. We suggest that both bone mineral density and biochemical examinations should be considered to be routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.

Outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered an optimal indication for liver transplantation (LT) because it may eliminate both the tumor and the underlying liver disease. The present study sought to compare cumulative survival, rate of HCC recurrence, and causes of death among patients with cirrhosis and HCC before and after the adoption of more restrictive criteria (Milan selection criteria) at the time of patient listing. Among 226 adult patients who received an elective liver transplantation between 1999 and 2005, 58 (27%) had a diagnosis of HCC at the time. The 38 patients who underwent transplantation for HCC in the period 1989 to 1998 were considered the "historical group." After LT (mean follow-up, 34 + 28 months), the cumulative survival rate was better among HCC versus non-HCC recipients (93% vs 71% at 1 year and 81% vs 67% at 3 years, respectively; P < .046), although the difference tended to attenuate after 5 years (66% vs 67%, respectively). Tumor recurrence (evaluated in patients surviving at least 3 months after LT) was observed in 10/31 in the historical group versus 4/53 among those who underwent transplantation after 1999. Among the causes of death, recurrence represented 50% in the old series and 23% in patients who underwent transplantation after 1999. Cumulative survival significantly improved among HCC patients who underwent transplantation after 1999 (93% vs 66% at 1 year and 81% vs 50% at 3 years; P < .00001). The 58 patients who underwent transplantation with a diagnosis of cirrhosis and concomitant HCC after 1999 showed even better survival than patients who underwent transplantation for end-stage liver disease without malignancy.

Cisplatin versus carboplatin in combination with mitomycin and vinblastine in advanced non small cell lung cancer. A multicenter, randomized phase III trial.

BACKGROUND: In advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1-2 months on median survival versus best supportive care. Chemotherapy seems to improve symptoms control, even if randomised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio. The aim of the present study is to evaluate the impact on QoL, substituting cisplatin, a pivot drug in NSCLC therapy, with carboplatin, an analogue with an improved toxicity profile. The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study. METHODS: Patients were randomized to receive MVP regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Cisplatin 100 mg/m2 d1) or MVC regimen (Mitomycin-C 8 mg/m2 d1, Vinblastine 4 mg/m2 d 1-8, Carboplatin 300 mg/m2 d1) every 3 weeks. The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 questionnaires before chemotherapy, after one cycle, after three cycles, and then every 6 weeks in the first 6 months and every 3 months thenafter. RESULTS: From September 1994 to July 1997, 153 consecutive patients were randomized to MVP (75 patients) or MVC arm (78 patients). Despite difficulties in carrying out and analysing QoL items in such patients, the global QoL evaluated by the Spitzer's questionnaire suggested an advantage for MVC regimen (P=0.05) and a significant difference was observed in global health subdomain (P=0.04). The disease-related symptoms improved with time, and the benefits lasted for the entire treatment period. When evaluated with the EORTC questionnaire there was significantly less nausea and vomiting (P=0.0001), appetite loss (P=0.01), insomnia (P=0.03), constipation (P=0.01) and peripheral neuropathy (P=0.01) in favour of MVC, and a trend for less hair loss (P=0.05). The advantage lasted for all the duration of chemotherapy. No differences were observed in global quality of life subdomain (P=0.40) between the two regimen. QoL was the first endpoint and the statistical power was inadequate to assess other parameters. However, we reported a response rate of 43.1 and 38.6%, respectively, in MVP and MVC arm (P=0.59) and a median survival of 10.2 and 7.2 months, respectively, for cisplatin and carboplatin arm (P=0.39). CONCLUSIONS: The carboplatin containing regimen (MVC) has a significant better toxicity profile than the cisplatin containing (MVP) regimen as proven both by the EORTC questionnaires and by the WHO toxicity data reported by physicians. No significant differences in terms of response rate, time to progression and overall survival were observed between the two regimen. The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL questionnaire. With the Spitzer's questionnaires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination. This difference, however, was not observed when the global quality of life was evaluated with the EORTC patients compiled questionnaires. A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC.

Gastric non-Hodgkin's lymphoma: analysis of 252 patients from a multicenter study.

AIMS AND BACKGROUND: The stomach is the most common site of primary extranodal non-Hodgkin's lymphoma (NHL) and no agreement has been reached so far on the best therapeutic approach. The main objects of this study were to report the long-term results and to evaluate the importance of some possible prognostic factors in a large series of patients. NHL was considered primary gastric if the main symptoms at presentation were those of gastric disease. METHODS AND STUDY DESIGN: We analyzed 252 consecutive patients treated between 1980 and 1993 in five hospitals in north-east Italy. According to the Working Formulation, 98 patients had low grade lymphoma, 59 intermediate grade (D to F), 81 G or high grade and 14 were not classified. The patients were divided into two groups: one including patients with limited disease (localized to the stomach or perigastric lymph nodes: 165 patients) and one including those with advanced disease (87 patients). The treatment consisted of surgery, chemotherapy, radiotherapy or combinations of these. Sixteen patients received only supportive therapy. RESULTS: The five-year overall survival was 65.4%: 80.3% for patients with limited disease and 36.7% for those with advanced disease (P < 0.0001). Among the limited disease patients the five-year survival was 84.4% for those treated with gastrectomy alone and 88.7% for those who received also adjuvant chemotherapy (P = 0.11). However, while chemotherapy did not improve survival in low grade NHL, it seemed to produce a better survival in the intermediate and high grade groups (P = 0.06). Twelve patients were treated with primary chemotherapy and the five-year survival was 71.2%. In multivariate regression analysis the most important variable for overall survival was surgery for the whole group of 252 patients (P < 0.0001), while it was age for the group with limited disease (P = 0.0008). CONCLUSIONS: Surgery alone can be curative for most patients with gastric lymphoma limited to the stomach or to the perigastric lymph nodes; surgery followed by chemotherapy seems to produce better results than surgery alone in intermediate and high grade lymphomas. Also a non-surgical approach with first-line chemotherapy is associated with a high rate of complete remissions and five-year survival. In advanced disease the five-year survival is similar to that of nodal NHL.

Expression of dipeptidylaminopeptidase IV/CD26 in peripheral blood lymphocytes of hemophilic subjects.

CD26 antigen, a 110 kDa membrane glycoprotein with exopeptidase activity (DAP IV), is an activation marker of T lymphocytes preferentially expressed on CD4+ memory cells and involved in T cell proliferation and IL-2 production after antigenic stimulation. We employed cytochemical and immunocytochemical techniques to study DAP IV/CD26 expression in circulating lymphocytes from 40 hemophilic patients, chronically treated with coagulation factors, in order to verify the possible involvement of this molecule in the immunological alterations of hemophilia. In all the hemophiliacs DAP IV activity was significantly lower than in the controls, independently of the quantity of blood transfused and previous exposure to viruses. This reduction may be responsible for the impaired proliferative response of lymphocytes to antigens and mitogens, notoriously observed in hemophilia. Whereas in the group of HIV- patients CD26 expression was similar to that of normal controls, in the 8 HIV+ hemophilic patients both percentages of positive lymphocytes and intensity of staining were significantly lower. In only 4 of the 8 cases was this deficit associated with CD4+ cell depletion. The significant selective loss of CD26 expression observed in HIV+ patients is probably an early event after HIV infection and seems to occur even before CD4 cell depletion. In conclusion, evaluation of DAP IV/CD26 might be a useful option for monitoring the immunological alterations of all hemophilic patients, HIV positive or not, chronically treated with coagulation factors.

Idarubicin and cytosine arabinoside in the induction and maintenance therapy of high-risk myelodysplastic syndromes.

BACKGROUND AND OBJECTIVE: Recently, the results of a few pilot studies have shown the efficacy of the association of idarubicin (IDA) and cytosine arabinoside (Ara-C), already successfully employed in acute myeloid leukemia (AML), for remission induction in patients with myelodysplastic syndrome (MDS). We set out to evaluate in a multicenter study the efficacy and tolerability of an intensive therapy with IDA and Ara-C in patients with RAEB and RAEB-t, the rate and duration of CR and the overall survival in adults treated with full doses and in the elderly treated with lower doses; furthermore, we investigated the efficacy of low-dose maintenance chemotherapy. METHODS: Pretreated adult patients with de novo RAEB and RAEB-t, meeting at least one of the following criteria, were included: neutrophils < 0.5 x 10(9)/L or moderate neutropenia with infectious episodes, platelets < 30 x 10(9)/L or moderate thrombocytopenia but with bleeding symptoms, transfusion > 4 red cell units/months, rapid increase of bone marrow blasts. Induction treatment consisted of a cycle with IDA and Ara-C. Adult patients less than 65 years old were treated with the following doses: Ara-C 1 g/m2/day i.v. 6-hour infusion, on days 1-4, IDA 10 mg/m2/day i.v., on days 1-3. Elderly patients (> or = 65 yrs) were treated with lower doses: Ara-C 1 g/m2/day 6 hours infusion, on days 1 and 2, IDA 10 mg/m2/day i.v., on days 1 and 2. Responders followed a consolidation course identical to induction. RESULTS: From February 1994 to February 1997, 25 patients were enrolled, 20 males and 5 females aged between 22 and 76, 10 were > or = 65 years old, 7 had RAEB and 18 had RAEB-t. Twelve cases (48%) achieved complete remission (CR), 7 cases (28%) achieved partial remission, 4 patients were resistant and two patients (8%) died during the aplastic phase. A significantly higher CR rate was found in younger patients (p = 0.036), while gender, FAB subtype, presence of Auer rods, cytogenetic findings, and the interval from diagnosis to treatment did not significantly influence CR achievement. INTERPRETATION AND CONCLUSIONS: Our results show that in de novo RAEB and RAEB-t, the employed treatment with IDA and Ara-C is associated with satisfactory frequency of response with acceptable toxicity.

Surgical second look in ovarian cancer: a randomized study in patients with laparoscopic complete remission--a Northeastern Oncology Cooperative Group-Ovarian Cancer Cooperative Group Study.

PURPOSE: The usefulness of extensive and repetitive surgery for patients with ovarian cancer still remains unproven (at least for some conditions). We planned an accurate prospective test of the hypothesis that patients with advanced-stage disease, after they had reached a clinical complete remission (CR), may benefit from surgical second look (SSL). PATIENTS AND METHODS: One hundred two patients in CR (as assessed by clinical findings, markers, and visualization by computed tomographic [CT] scan and laparoscopy), after initial debulking and first-line chemotherapy, were randomized to two arms, which were well balanced for predictive criteria such as age, stage at presentation, histology, grading, date of randomization, and residua after first surgery. Forty-eight patients were randomly assigned to receive follow-up evaluation only, while 54 were assigned to receive second surgery (eight of them refused). Of 46 surgical patients, 35 had negative and 11 positive surgical findings (24% clinically false-negative). RESULTS: Despite the microscopic residua found at open surgery, and the fact that the patients were then treated with second-line chemotherapy, SSL did not increase the probability of survival in this setting. In an analysis of the results according to the intention-to-treat criteria, after a 60-month follow-up period, the overall survival rates in the two groups of patients (SSL v no SSL) were 65% and 78%, respectively (P = .14). Multivariate analysis according to predictive criteria confirmed there was no significant difference between the two groups (P = .39). CONCLUSION: Our study shows the following: (1) our second-line treatment is scarcely effective; (2) SSL accurately defines complete responders to first-line chemotherapy; (3) SSL per se does not prolong survival; and (4) if confirmed, a less invasive procedure could replace SSL as a valuable method in new first-line regimens in ovarian cancer patients with clinical CR confirmed by laparoscopy.

Idarubicin and cytosine arabinoside in the induction and maintenance therapy of high-risk myelodysplastic syndromes.

BACKGROUND AND OBJECTIVE: Recently, the results of some pilot studies have shown the efficacy of the association of idarubicin (IDA) and cytosine arabinoside (Ara-C), already successfully employed in acute myeloid leukemia (AML), for remission induction in patients with myelodysplastic syndrome (MDS). We set out to evaluate in a multicenter study the efficacy and tolerability of an intensive therapy with IDA and Ara-C in patients with RAEB and RAEB-t, the rate and duration of complete remission, and the overall survival in adults treated with full doses and in the elderly treated with lower doses; furthermore, we investigated the efficacy of low-dose maintenance chemotherapy. METHODS: Pretreated adult patients with de novo RAEB and RAEB-t, meeting at least one of the following criteria, were included: neutrophils < 0.5 x 10(9)/L or moderate neutropenia with infectious episodes, platelets < 30 x 10(9)/L or moderate thrombocytopenia with bleeding symptoms, transfusion > 4 red cell units/months, rapid increase of bone marrow blasts. Induction treatment consisted of a cycle with IDA and Ara-C. Adult patients less than 65 years old were treated with the following doses: Ara-C 1 g/m2/day i.v. 6-hour infusion, on days 1-4, IDA 10 mg/m2/day i.v., on days 1-3. Elderly patients (> or = 65 yrs) were treated with lower doses: Ara-C 1 g/m2/day 6 hours infusion, on days 1 and 2, IDA 10 mg/m2/day i.v., on days 1 and 2. Responders followed a consolidation course identical to induction. RESULTS: From February 1994 to February 1997, 25 patients were enrolled, 20 males and 5 females aged between 22 and 76, 10 were > or = 65 years old, 7 had RAEB and 18 had RAEB-t. Twelve cases (48%) achieved complete remission (CR), 7 cases (28%) achieved partial remission, 4 patients were resistant and two patients (8%) died during the aplastic phase. A significantly higher CR rate was found in younger patients (p = 0.036), while gender, FAB subtype, presence of Auer rods, cytogenetic findings, and the interval from diagnosis to treatment did not significantly influence CR achievement. INTERPRETATION AND CONCLUSIONS: Our results show that in de novo RAEB and RAEB-t, treatment with IDA and Ara-C is associated with satisfactory frequency of response with acceptable toxicity.

[The emotive and cognitive reactions in temporary pharmacological menopause]. / Reazioni emotivo-cognitive in menopausa farmacologica temporanea.

The authors have attempted to evaluate the extent to which menopausal crisis is linked to hypoestrogenism and the extent to which it is linked to the socioenvironmental context in which it takes place. The study analyses emotional and cognitive aspects in a group of women in temporary menopause which was pharmacologically induced for therapeutic purposes. The study was carried out in 30 patients suffering from benign gynecological pathologies receiving ovarian steroidogenesis-blocking treatment. Treatment consisted of a subcutaneous administration of a Gn-Rh analog every 28 days for 6 months. After having collected information regarding the symptoms that appeared following the administration of therapy, the authors evaluated the emotive (anxiety and depression) and cognitive (short-term memory and concentration) conditions of patients using psychometric reactives performed during the first check-up, and then repeated at the 3rd, 5th and 7th control visit: the State-Trait-Anxiety-Inventory to assess trait anxiety and state anxiety; scale D of the Minnesota Multiphasic Personality Inventory to assess depression; the sub-test for memory of figures from Wechsler-Bellevue Intelligence Scale to evaluate short-term memory; the Toulouse-Pieron reactive to evaluate attention and concentration. The results obtained were analysed statistically using Student's t-test and Pearson's coefficient. An analysis of the data shows that, after the first doses of the drug stress trends to diminish from the high levels recorded at the first visit, stabilising at normal values throughout treatment. Like anxiety and depression, concentration and memory do not show marked variations.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient aplasia preceding adult acute lymphoblastic leukemia.

A 62-year-old woman developed common acute lymphoblastic leukemia (ALL) after spontaneous recovery from transient marrow aplasia. Although the mechanisms underlying bone marrow suppression in acute leukemia are obscure, it is important to know that transient aplasia may be observed as a prodromal feature in ALL in adult patients as well as in children.