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Biomedical subjects

D Bertoloni

Publications and source records attributed to D Bertoloni.

15 recordsLinked to original sources
PubMed1994

Study of prognosis in Waldenström's macroglobulinemia: a proposal for a simple binary classification with clinical and investigational utility.

Prognostic evaluation of Waldenström's macroglobulinemia (WM) is unreliable, few studies considered prognostic factors in WM and only one was derived from a multivariate analysis. One hundred forty-four retrospective, previously untreated patients with clinically overt WM were studied to learn whether overall survival was related to any of the various clinical features presented at diagnosis. Patients were homogeneously treated with intermittent doses of chlorambucil for as long as this showed an effect on the monoclonal component. The population was randomly subdivided into a 90-patient exploratory sample, on whom investigation would be conducted, and in a 54-patient test sample, on whom the results would be validated. In the exploratory sample univariate analysis identified the following parameters as the most important for prognosis: age (< or > or = 70 years), platelet count (< or > or = 120 x 10(9)/L), presence or absence of an abnormal number of red blood cells in the urine, hemoglobin concentration (< or > or = 9 g/dL), erythrocyte sedimentation rate (< or > or = 110 mm at first hour), presence or absence of cryoglobulinemia and of weight loss. Cox multivariate analysis showed that only hemoglobin, age, weight loss, and cryoglobulinemia independently affected survival. These four clinical variables were also shown to be able to discriminate survival significantly in the test sample. Moreover, it was possible to demonstrate (both in the exploratory and the test sample) that clear-cut, albeit dichotomic, survival discrimination can be reached with the presence at diagnosis of either no more than one, or any two or more, of these four prognosticators. These simple clinical criteria could be the basis of an initial binary, prognostic classification of WM, which could help in differentiating therapy according to the severity of the disease, and in properly designing future clinical trials.

Adult↗
PubMed1992

Progressive necrotic myelopathy as a paraneoplastic syndrome: report of a case and some pathogenetic considerations.

Progressive necrotic myelopathy is a syndrome characterized by a spotty necrotic degeneration of the whole spinal cord in both anterior and posterior horns. This syndrome was recorded in a man suffering from a lymphoplasmatocytoid lymphoma. Whilst the usual evolution of this neurological syndrome is inexorably fatal, our case had a better outcome, due to the good response of the neoplasm to therapy. Progressive necrotic myelopathy is an uncommon complication of cancer, but it is probably incorrectly recognized in a number of cases. Two possible pathogenetic hypotheses are suggested: an autoimmune or an infective mechanism.

Autoimmune Diseases↗
PubMed1991

Changing clinical presentation of multiple myeloma.

We compared the presentation features of three series of patients with multiple myeloma diagnosed between 1960 and 1971 (Kyle R, Mayo Clin Proc, 1975, 50, 29, n = 869), 1972 and 1986 (Clinica Medica, University of Pavia, n = 345) and 1987 and 1990 (Cooperative Group for Study and Treatment of Multiple Myeloma, n = 341). In the most recently diagnosed patients, the percentage of those who had symptoms related to multiple myeloma (i.e. any of bone pain, systemic symptoms, disturbances related to hypercalcemia, neurological involvement and hyperviscosity) was reduced (90 vs. 86 vs. 66%) (P less than 0.001), while the percentage of asymptomatic patients diagnosed by chance was increased (not reported, and 14 vs. 34%). In the most recent series, a lower percentage of spontaneous bone pain (68 vs. 60 vs. 37%, P less than 0.001) paralleled a lower incidence of advanced bone disease (osteolyses and pathological fractures, 60 vs. 64 vs. 34%), and renal failure (serum creatinine greater than 1.2 mg/dl) was also less common (56 vs. 44 vs. 33%, P less than 0.01), at least partially due to a decreased incidence of both hypercalcemia (30 vs. 20 vs. 18%, P less than 0.001) and of hyperuricemia (serum uric acid greater than 7 mg/dl, 47 vs. 32 vs. 26%, P less than 0.01). Systemic symptoms (weakness, infections, fever or weight loss) were reported more seldom by recently diagnosed patients, due to a decreased frequency of anaemia (haemoglobin less than 12 g/dl), leukopenia and thrombocytopenia, as well as of the systemic effects of bone pain and of renal insufficiency. These data indicate that multiple myeloma is diagnosed earlier now than in the past, and this must be taken into account when comparing survival data in treated series.

Adult↗
PubMed1991

A plea to overcome the concept of "staging" and related inadequacy in multiple myeloma.

From a retrospective multivariate study on 107 multiple myeloma (MM) patients, serum beta 2-microglobulin (beta 2M) proved to be the best prognostic discriminator, better than each of the currently used staging systems (Durie and Salmon's [DS], Merlini, Waldenström and Jayakar's [MWJ] and the British Medical Research Council's [BMRC]). The predictive ability of each staging system is better improved by combining consideration of beta 2 M as a continuous rather than a binary variable (even at its best prognostic cut-off). The combination of BMRC with beta 2 M demonstrated the highest prognostic value, followed by those involving DS or MWJ. Ease and measurability of clinical parameters at diagnosis, parametric type of statistical model assumed for description of survival, and supply of direct estimate of expected survival are the characteristics of the MWJ system that suggest it is best able to integrate beta 2 M correctly in a prognostic index. The basic concepts and the clinical use of the available staging systems for MM are criticized along the following lines: a) the need to include new and homogeneously weighted parameters in future prognostic systems -b) the lack of direct correspondence between treatment requirements (according to stage) and available therapeutic resources -c) evidence of the rough stratification of the actual survival expectancy, as permitted by the current staging systems. A direct, and as accurate as possible estimate of prognosis--based on easy and measurable parameters evaluable at diagnosis--should replace the current classification of patients according to stages. This estimate should mark the clinical evaluation at diagnosis, should flexibly indicate treatment even according to different protocols or centers, and should allow very accurate statistical corrections for different survival expectancy at diagnosis when evaluating different treatments in clinical trials.

Adult↗
PubMed1991

[Spontaneous remission of visceral metastases of hypernephroma after nephrectomy. Description of a case and review of pathogenetic hypotheses].

We describe an absolutely spontaneous regression of visceral metastases from a renal carcinoma, following nephrectomy, in a 46 years old patient, who is at present in a complete uninterrupted remission for 39 months. After a literature review we point out the rarity of this event and emphasize its absolute spontaneity. Moreover, we suggest some considerations about the possible pathogenetic mechanisms of this unexpectedly positive outcome. Between these, because of the strongly positive psychologic attitude of the patient, the psycho-neuro-immunologic one is suggestive.

Bone Neoplasms↗
PubMed1990

The role of surgery in the multimodal treatment of primary gastric non-Hodgkin's lymphomas. A report of 76 cases and review of the literature.

Seventy-six patients with primary gastric non-Hodgkin's lymphomas (PGL) were diagnosed, and 75 were treated between 1975 and 1985. According to the Working Formulation 22 patients had low-grade malignant histologic subtypes, 27 intermediate-grade, and 27 high-grade. Twenty-four cases were diagnosed by endoscopic biopsies, 52 through laparotomy biopsies. Forty-five underwent subtotal or total gastric resection; seven were considered unresectable at laparotomy; 23 did not undergo surgery because of the high operative risk, mainly due to advanced age and coexisting diseases; and one died of myocardial infarction a few days after admission, before starting therapy. All patients who did not undergo laparotomy were staged with bipedal lymphangiography or abdominal ultrasonography and/or computed tomography. Stage, evaluated according to the criteria of Musshoff, was I or II1 in 16 cases, II2 in five, and IV in the remaining 55. Treatment modalities included surgery (S), chemotherapy (CT), radiotherapy (RT), and combinations thereof in the following proportions: only S in ten cases, S + CT in 32 cases, S + RT in one case, S + CT + RT in two cases, CT only in 25 cases, CT + RT in five cases. No substantial differences in response to therapy and in survival were found in relation to the different treatments. Ten-year survival was 43% in Stage I or II and 20% in Stage IV. Of the 45 resected patients, five postoperative deaths were recorded (11%). No bleeding or perforations were observed in the 30 unresected patients, and survival of such cases compared with that of the resected ones. These findings, together with data from the literature, suggest that some of the advantages claimed for surgery in PGL (debulking and abatement of the risk of perforation or hemorrhage during CT or RT) have been overestimated in relation to the intrinsic surgical risk and to the possibility of anticancer therapy. Gastric resection may still be unavoidable as a diagnostic procedure in a minority of cases and may represent the primary therapeutic procedure in clinically assessed early-stage and low-risk patients, but it cannot be considered mandatory whenever possible merely for debulking purposes or to obviate possible perforation or hemorrhage. The CT and/or RT can be effective in unresected and even bulky cases, providing minimal risk of severe hemorrhage or perforation.

Adolescent↗
PubMed1990

Night sweats in Hodgkin's disease. A manifestation of preceding minor febrile pulses.

The authors verified the hypothesis regarding an unawareness of possible febrile alterations during night sleep in patients with Hodgkin's disease who complain of night sweats as their only symptom. In these patients, body temperature was monitored by means of a 0.01 degrees C-sensitive linear transducer coupled with a digital multimeter. The palm of the hand (after it was passively closed in a fist by a full bandage) was the body site where temperature measurement was found to be most comfortable for a sleeping patient and independent of movements during sleep. A good correlation was found between the hand temperature taken with this technique and oral temperature. Of six patients with sweating as their only symptom, sweating recurred during the night in four and during the afternoon in the other two. In all patients sweating was preceded by a critical 0.5 to 1.5 degrees C increase in hand temperature, which took place no more than 30 minutes before sweating. Those with nocturnal sweats awakened during the subsequent sweating-related, rapid temperature decrease. These results are consistent with the occurrence of slight unperceived febrile pulses that precede sweating. The only peculiarity of night sweats consists in the higher probability that a preceding slight temperature rise may not be perceived by a sleeping patient, who is more likely to be awakened by the discomfort of the subsequent sweating. This would also explain the small prognostic significance of these sweats, which is the same as that of the preceding fever. These results are discussed in light of the increasing clinical evidence that patients with Hodgkin's disease are often affected by an instability of the thermoregulatory hypothalamic centers.

Adolescent↗
PubMed1989

Ploidy and proliferative activity measurement by flow cytometry in non-Hodgkin's lymphomas. Do speculative aspects prevail over clinical ones?

Paraffin-embedded lymph node biopsies from 107 patients with newly diagnosed non-Hodgkin's lymphomas were examined for cell DNA content and proliferative activity (as percentage of S-phase cells) by means of flow cytometry. Patients were diagnosed between 1975 and 1985 and were homogeneously treated according to the grade of histologic malignancy. Cytofluorimetric data were studied with regard to their correlation with histology (classified and reviewed according to both Kiel and Working Formulation criteria), clinical stage, presence of constitutional symptoms, presence of bulky disease, sex, age, and the following laboratory data measured at diagnosis: erythrocyte sedimentation rate, hemoglobin, serum lactic dehydrogenase and serum albumin concentration. Aneuploidy was more frequent in the high grade malignant subtypes and in the miscellaneous group but showed no correlations with the other clinical parameters studied. Proliferative activity demonstrated a wide variation of data but a trend was evident toward higher proliferative values in the more severe histologic subtypes. The survival discrimination allowed by high- and low-grade malignant histology is exactly reproduced when highly and slowly proliferating lymphomas are considered (greater than or less than or equal to 12% of S-phase cells). These results, analyzed with those in the literature, suggest that measurements of ploidy and proliferative activity add little independent information to what is already provided by current histologic classifications, mainly as far as clinical evaluation and prognosis are concerned. Cytokinetic-aided therapeutic choices can be usefully proposed in a restricted number of cases. Improvement of the available lymphoma classifications through a better integration of ploidy and cytokinetic data with immunologic, genetic and histologic findings is still an object to be pursued in cytometric studies.

Adolescent↗
PubMed1989

Increasing interdependency of prognosis- and therapy-related factors in Hodgkin's disease.

Two subsequent series of patients with Hodgkin's disease (HD) treated according to different therapeutic plans were compared: the study made it possible to analyze the role played by therapy in influencing the individual importance of a group of well-known prognostic factors. Study 1 concerned 667 patients treated in the period 1971-1979 without special measures for mediastinal bulky disease and with four-drug chemotherapy regimens (MOPP, COPP, ABVD) for stage B or IV. Study 2 included 220 patients treated between 1980 and 1984 with combined sandwich chemoradiotherapy when mediastinal bulk was present, and with eight-drug alternating chemotherapy regimens for stages B or IV (MOPP/ABVD, CcVPP/ABVD). Distribution of epidemiologic and clinical characteristics as well as staging accuracy were comparable in the two series. Only sex, serum albumin at onset and success or failure in achieving complete remission showed the same ability to discriminate survival in both studies. Age, stage and histology retained a reduced role in Study 2, where it was found they could be handled as binary variables, i.e. more or less than 50 years of age, stage IV or other stages, lymphocyte depletion histotype or other types. The influence of B symptoms on survival was sharply decreased in patients treated with alternating chemotherapy regimens, whereas combined sandwich therapy showed a truly leveling effect on the role of mediastinal bulk, which has to be considered a very unfavorable factor with other treatments. In HD the evaluation of clinical findings with respect to their impact on prognosis is crucial for validating and graduating the staging process, and for matching the intensity of the therapy to the needs of the patient. The ongoing evolution in the roles of single prognostic factors due to therapy needs periodic reevaluation for proper adjustments of therapeutic strategies.

Adolescent↗
PubMed1988

Hodgkin's disease prognosis: a directly predictive equation.

586 patients with Hodgkin's disease diagnosed between 1970 and 1979 were staged and treated in the same way. Multivariate analysis was used to delineate the prognostic roles of several clinical features at diagnosis. A multiple regression analysis was applied to an exponential model for survival-time distribution, which proved to fit the data accurately. Several clinical characteristics were studied and those that could singly discriminate survival significantly were chosen as predictive variables for the multiple regression. These were: sex, age, stage, histological subtype, presence of constitutional symptoms, mediastinal mass, and erythrocyte sedimentation rate (ESR), and haemoglobin and serum albumin concentrations. ESR, stage, histological subtype, and age proved to be the best prognostic factors, while sex and albumin had minor value. The presence of symptoms, mediastinal bulk, and haemoglobin were not so important. A linear equation for the six variables was derived to calculate the estimated median survival time for any given patient. This equation was validated on an external group of 179 similar patients.

Actuarial Analysis↗
PubMedDate not supplied

[ProMACE-MOPP vs. ProMACE-CytaBOM polychemotherapies in the treatment of large-cell and unclassifiable non-Hodgkin's lymphomas].

The results of two distinct and successive clinical pilot studies investigating feasibility of aggressive chemotherapy in large cell and unclassified non-Hodgkin's lymphomas are reported. In the first study (1986-87) the ProMACE-MOPP chemotherapy (P-M), a 2nd generation regimen, was administered to 10 patients, whereas in the second study (1987-88) the ProMACE-CytaBOM schedule (P-C), a 3rd generation regimen, was administered to 13 patients. The clinical and prognostic features of the two groups of patients were quite comparable, the only difference being the different follow-up times (median: 43 vs 26 months). The number of complete remissions, freedom from relapse and overall survival were slightly better in the P-M group, with-out a statistically significant difference, despite the longer follow-up time. Hematological toxicity was higher in the P-M study, while gastrointestinal (mucositis, hepatic transitory damage) and neurological toxicity (peripheral neuritis) were somewhat lower. In conclusion, the P-M regimen is worth considering for the treatment of high grade malignant lymphomas, although it was not recently designed and is not widely used at present.

Adolescent↗
PubMedDate not supplied

MOPP/ABV/CAD chemotherapy with and without recombinant human granulocyte-macrophage colony stimulating factor in untreated, unfavorable prognosis Hodgkin's disease.

Seventeen consecutive patients with previously untreated poor prognosis Hodgkin's disease (clinical stage II and III with systemic symptoms, and stage IV) received 6 courses of aggressive chemotherapy, with (9 patients) and without (8 patients) the addition of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF). Chemotherapy (MOPP/ABV/CAD regimen) included full doses of nitrogen mustard, lomustine (CCNU), vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine and bleomycin, and was administered between days 1 and 15 of each course. Course were planned for 28-day intervals. rhGM-CSF was given at a dose of 5 micrograms/kg/day subcutaneously from day 16 to 26 of each course. With cytopenia (i.e. white blood cell, WBC, count < 3.0 x 10(9)/L and/or platelet count < 100 x 10(9)/L) delaying courses was preferred to administering reduced drug dosages. Substantial delays (ranging from 7 to 28 days) in delivering cytostatics were necessary between 70% of courses. The cumulative mean number of days for which the courses had to be delayed before completing the 6 MOPP/ABV/CAD courses was 57. The percentage of planned doses of cytotoxic drugs (nitrogen mustard, melphalan, epidoxorubicin, procarbazine) actually administered was 92%. Causes of treatment delay were presented by leucopenia in 82% and by leuco-thrombocytopenia in 23% of the courses. The WBC nadir was constantly encountered at day 20-21 following completion of courses, and slightly worsened with subsequent courses. The decrease in platelet values was milder than that in WBC counts. There were no differences in any of the above parameters between patients treated with MOPP/ABV/CAD alone or followed by rhGM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Estimate of expected survival at diagnosis in Hodgkin's disease: a means of weighting prognostic factors and a tool for treatment choice and clinical research. A report from the International Database on Hodgkin's Disease (IDHD).

PURPOSE: The aim was to identify a mathematical model that, when fitted with the survival time distribution of a Hodgkin's disease population, would provide a reliable estimate of expected survival at diagnosis for any new Hodgkin patient. This model would be based upon a multivariable selection of the best prognostic factors evaluable at diagnosis and its forecast could be of assistance in the choice of treatment. METHODS: The study sample consisted of the 5,023 patients whose basic clinical information was collected into the IDHD. These were people treated with standard protocols over the last two decades in 18 institutions. Several survival time distributions (exponential, Weibull, Gompertz, log-logistic and log-normal) were investigated to find the one that best fit the data and to relate its parameters to patient prognostic characteristics. RESULTS: The log-normal model provided the best fit for the data. The most statistically significant prognostic covariates were stage, age, histotype, B symptoms, serum albumin, sex and involved area distribution. Mediastinal, extranodal or bone marrow involvement, erythrocyte sedimentation rate, hemoglobin, serum alkaline phosphatase and lactate dehydrogenase did not add significant information. An equation containing these seven variables was derived to estimate median survival. Five distinct prognostic classes were identified by four cut-off values for this estimate. CONCLUSIONS: Direct use of estimated median survival or allocating each patient into one of the five prognostic classes allows better tailoring of clinical strategies according to prognostic characteristics, more accurate patient stratification and evaluation of results in clinical trials and metaanalyses. Instructions are given for using this tool for both clinical and investigational purposes.

Adolescent↗
PubMedDate not supplied

Primary splenic lymphoma: does it exist?

The number of primary splenic lymphomas being reported is increasing despite the rarity of this malignancy, but what really constitutes a lymphoma arising primarily in the spleen is still a matter of discussion. The authors choose the "restrictive" definition of a lymphoma involving the spleen and the splenic hilar lymph nodes only. In this way, the risk of epidemiologic or clinical overestimation is avoided. The clinical features of this condition are characterized by non specific symptoms and signs, while the prevailing histology is that of a low-grade or intermediate-type lymphoma. Disease spreading outside of the spleen and its hilar lymph nodes is the single most important factor associated with an unfavorable prognosis. From this usual clinical picture, two distinct nosologic entities can be outlined on the basis of histologic and immunologic peculiarities: splenic lymphoma with circulating villous lymphocytes and marginal-zone splenic lymphoma. The former arises from follicular center cells and is characterized by hypersplenism, variable percentages of circulating villous lymphocytes and, frequently, a monoclonal gammopathy. The latter originates from a peculiar splenic B-cell structure separated by the mantle zone. The proliferating cells are medium-sized KiB3-positive lymphocytes with round or cleaved nuclei and pale cytoplasm, which surround follicular centers and infiltrate the mantle zone. It is interesting that marginal-zone lymphoma cells share some of the characteristics of the lymphocytes involved in both lymphomas of mucosa-associated lymphoid tissue and the B-monocytoid lymphomas. Splenectomy is still the most effective therapy for all primary splenic lymphomas.

Humans↗