bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine Receptor Signal Transduction Mechanisms in Immuno-Hematopoietic Cells
Authors: Chiarugi Vincenzo , Sbarba Persio Dello , Magnelli Lucia , Chiarugi Paola , Pacini Stefania , Ruggiero Marco
Published: April 2018

Novel aspects of cytokine receptor signal transduction are discussed and cytokine receptors classified based on ligand-dependent signalling. An introductory section presents an overview of the role of cytokines in hematopoiesis. A brief explanation of basic concepts, such as redundancy, pleiotropy, synergism, etc., important for the understanding of cell response to cytokines, is also included. Three of five classes of receptors show the involvement of tyrosine kinase activity as the key step in signal transduction. The importance of tyrosine phosphorylation in cellular response to cytokines is pointed out.
The Basement Membranes in Sarcomatoid Carcinomas. An Immunohistochemical Study
Authors: Guarino Marcello , Squillaci Salvatore , Reale Domenico , Micoli Giorgio
Published: April 2018

Aims

Eight sarcomatoid carcinomas from various anatomical locations were investigated by immunohistochemical staining to laminin, type IV collagen and heparan sulfate proteoglycan, to study the characteristics of basement membranes at the interface between carcinomatous and sarcomatous tissues.

Methods

Paraffin wax embedded tissue sections from representative tumor samples have been stained with specific antibodies, using the peroxidase-antiperoxidase technique.

Results

In all cases several interruptions or discontinuities of the basement membrane staining pattern were seen. In 4 cases, larger defects or complete loss of staining was also noted. At these places, the boundaries between carcinomatous and sarcomatous tissue were often blurred.

Conclusions

Disruption and loss of basement membranes at interface between carcinomatous and sarcomatous tissues is a frequent finding in sarcomatoid carcinomas. These changes could be consistent with an epithelial origin of the sarcomatous component in these tumors by means of an epithelial-mesenchymal conversion mechanism.
Radioendocrine Therapy of Brain Tumors with the Long Acting Opioid Antagonist Naltrexone in Association with Radiotherapy
Authors: Lissoni Paolo , Meregalli Sofia , Fossati Vittorio , Barni Sandro , Tancini Gabriele , Barigozzi Pierluigi , Frigerio Franco
Published: April 2018

Aims and Background

Malignant gliomas remain untreatable as the different therapeutic combinations are generally only palliative. Recent experimental evidence suggests that endogenous opioid peptides are involved in brain tumor growth. The aim of the present study was to evaluate the effect on survival of concomitant administration of the long-acting opioid antagonist naltrexone (NTX) in patients with malignant astrocytomas treated with radiotherapy (RT).

Methods

21 patients with high grade malignant gliomas were randomized to receive RT alone or RT plus NTX. The dose of RT was 60 Gy. NTX was given orally at a dose of 100 mg every other day without interruption until disease progression.

Results

The objective tumor regression rate in patients treated with RT plus NTX was higher than that of those treated with RT alone but not significantly so. On the contrary, the percentage of survivals at 1 year was significantly higher in patients treated with RT plus NTX than in those treated with RT alone (5/10 vs 1/11, P < 0.05). NTX therapy was substantially well tolerated in most patients.

Conclusions

The finding of longer survival in brain tumor patients treated with RT plus NTX than in those who received RT alone suggests in vivo involvement of endogenous opioid peptides in regulating the growth of malignant astrocytomas.
Prevention by L-Carnitine of Interleukin-2-Related Cardiac Toxicity during Cancer Immunotherapy
Authors: Lissoni Paolo , Galli Maria Albina , Tancini Gabriele , Barni Sandro
Published: April 2018

Aims and Background

Cardiac toxicity has been observed during IL-2 cancer immunotherapy. Because of its trophic action on the myocardial tissue, the use of L-carnitine has been evaluated during IL-2 therapy in advanced cancer patients with clinically important cardiac diseases.

Methods

The study included 30 cancer patients, who were randomized to treatment with IL-2 alone or IL-2 plus L-carnitine (1000 mg/day orally). IL-2 was injected subcutaneously at a daily dose of 6 million IU for 5 days/week for 4-6 weeks.

Results

The percentage of cardiac complications was significantly lower in patients concomitantly treated with L-carnitine than those receiving IL-2 alone (0/15 vs 4/15; P < 0.05), whereas no difference was seen in mean creatine phosphokinase levels on study.

Conclusions

The results would suggest that L-carnitine may be used successfully to prevent cardiac complications during IL-2 immunotherapy in cancer patients with clinically relevant cardiac disorders. Since cardiac metabolism depends mainly on fatty acid oxidation, the stimulatory role of L-carnitine on fatty acid oxidation could explain at least in part its ability to prevent heart disturbances in response to IL-2 administration.
Intestinal-Type Adenocarcinoma of the Sinonasal Tract: A Clinicopathologic Study of 18 Cases
Authors: Urso Carmelo , Ninu Maria Benedetta , Franchi Alessandro , Paglierani Milena , Bondi Roberto
Published: April 2018

Background

Intestinal-type adenocarcinoma (ITAC) of the nose and paranasal sinuses is a relatively rare tumor. It commonly affects subjects exposed to wood or leather dust.

Methods

The authors present the clinicopathologic findings of 18 cases of sinonasal ITACs and review the proposed histologic classifications.

Results

All patients, except one, were males; mean age was 60 years (range, 41-79); in 9 cases an occupational exposure to wood or leather dust was found. Common presenting symptoms were epistaxis, nasal obstruction and rhinorrhea. Histologically, tumors were divided into four groups: well-differentiated (G1) ITACs = 3 cases; moderately differentiated (G2) ITACs = 8 cases; poorly differentiated (G3) ITACs = 2 cases; mucinous (M) ITACs = 5 cases. Immunocytochemically, 16/17 cases were positive for carcinoembryonal antigen, 1/17 for somatostatin, and 0/16 cases for gastrin.

Conclusions

Sinonasal ITACs are aggressive tumors, often diagnosed in a relatively advanced stage. Owing the close similarity of the microscopic aspects, a histologic classification of ITACs analogous to that of colonic adenocarcinomas is proposed.
Predisposing Genes in Breast and Ovarian Cancer: An Overview
Authors: Smith Simon A. , Ponder Bruce A.J.
Published: April 2018

The isolation of genes that predispose to familial disease is an important goal in cancer research. The identification of such genes « opens up » the possibility of genetic diagnosis in families so that individuals who are at risk of cancer through inheriting a predisposing mutation can be Identified. Genes that are involved in familial cancer syndromes may also be important in the pathogenesis of sporadic forms of the disease, which are often more common. In the search for genes that predispose to familial breast and ovarian cancer much recent progress has been made. A locus on the long arm of chromosome 17, in the interval 17q12-21, has been identified by genetic linkage, and appears to be responsible for disease in approximately 40 % of breast cancer families and most families that contain breast and ovarian cancer. The region containing this locus, which has been called BRCA1, has been narrowed to a 3-4 cM interval defined by THRA1, the thyroid hormone receptor locus alpha, and D17S183, an anonymous microsatellite polymorphism. Loci other than BRCA1 that have been identified appear not only to predispose to breast and/or ovarian tumors, but to tumors at other sites too. A new locus has been identified on chromosome 2 which is linked to hereditary non-polyposis colorectal cancer (HNPCC). Families with HNPCC are also at risk of endometrial cancer and tumors of the ovary, amongst other cancer sites. Finally, mutations in the p53 gene are inherited in families with Li-Fraumeni syndrome, a rare cancer syndrome predisposing to breast tumors, sarcomas, leukemia and other cancers. Li-Fraumeni syndrome is also the only inherited cancer syndrome that predisposes at least in part to breast cancer where the actual predisposing gene is known. For the other cancer syndromes, the cloning of the predisposing genes is eagerly awaited.
Histological Evaluation of Thyroid Carcinomas: Reproducibility of the «Who» Classification
Authors: Fassina Ambrogio S. , Montesco Maria C. , Ninfo Vito , Denti Paolo , Masarotto Guido
Published: April 2018

Aims and Backgrounds

Thyroid carcinomas display several pathologic features, show different behavior and necessitate different treatment; thus correct classification is mandatory.

Methods

The kappa statistic was used as a measure of agreement in a panel of seven pathologists who reviewed 200 cases of thyroid tumors.

Results

Overall agreement was 83 % (k = 68). Good agreement was found for anaplastic (k = 0.85) and papillary carcinomas (k = 0.81); agreement for medullary carcinoma was acceptable (k = 0.80), suboptimal for other (k = 0.67), and poor for follicular carcinoma (k = 0.54).

Conclusions

Central pathology review of thyroid carcinomas is recommended when clinical and epidemiologic trials are planned.
Ductal Adenocarcinoma of the Pancreas: Clinicopathologic Features and Survival
Authors: Sperti Cosimo , Bonadimani Bruno , Pasquali Claudio , Piccoli Antonio , Cappellazzo Francesco , Rugge Massimo , Pedrazzoli Sergio
Published: April 2018

Aims and Background

The prognosis after surgical resection for pancreatic cancer has not been clearly defined because conflicting results have been reported.

Methods

Fifty-five patients who underwent surgical resection for pancreatic carcinoma between 1970 and 1987 were retrospectively reviewed to determine factors influencing long-term survival.

Results

The actuarial 5-year survival rate for all 55 patients was 12.5 %. Type of operation, tumor stage, direct extension into adjacent organs, grading and lymph node involvement were found to significantly influence survival. Age, sex, tumor site, size, invasion into peripancreatic tissue, invasion of lymphatic vessels and small veins, perineural Infiltration, tumor necrosis, round cell infiltrate at the tumor margin, associated chronic pancreatitis, and atypia of pancreatic ductal epithelium demonstrated no predictive capacity. No 5-year survival was observed among the patients who underwent vascular resection. Three of 9 patients who underwent left-sided pancreatectomy for cancer of the tail of the pancreas survived more than 5 years. Multivariate analysis confirmed that lymph node involvement, moderate-poor histologic tumor differentiation, and treatment with total pancreatectomy were signicantly associated with a worse prognosis.

Conclusions

Lymph node status, grading of the tumor and type of operation have a significant impact on prognosis in resected pancreatic cancer.
Immunotherapy with Low-Dose Subcutaneous Interleukin-2 plus Beta-Interferon as a Second-Line Therapy for Metastatic Colorectal Carcinoma
Authors: Barni Sandro , Lissoni Paolo , Ardizzola Antonio , Vigoré Luigi , Vezzo Roberto , Rescaldani Roberto , Tancini Gabriele
Published: April 2018

Aims and Background

Beta-interferon (β-IFN) has been proven to influence some IL-2-induced immune effects. On the basis of these experimental data, we evaluated the immunobiologic effects of an association between very low-dose IL-2 and β-IFN in advanced cancer patients.

Methods

The study was performed in 15 metastatic colon cancer patients, who progressed in response to a first-line chemotherapy with 5-FU plus folates. IL-2 was given subcutaneously at a daily dose of 3 million IU in the evening for 6 days/week for 4 weeks. β-IFN was injected subcutaneously at a dose of 3 million U/day for 7 days before the first IL-2 injection, then thrice/week until the end of IL-2 administration. In nonprogressed patients, a second cycle was given after a 14-day rest period.

Results

No objective tumor regression was seen. Stable disease was obtained only in 2/15 patients; the other 13 progressed. Toxicity was low in all cases. Natural killer cell and T-activated lymphocyte mean number significantly increased during the immunotherapy. Lymphocyte and eosinophil mean number also increased, without, however, significant differences. IL-2-induced suppressive events, consisting of an increase in T-suppressor cell number, and soluble IL-2 receptor levels were not blocked by β-IFN.

Conclusions

The study showed that the concomitant administration of β-IFN may determine an improvement in the immune performance in metastatic cancer patients treated with very low-dose IL-2, even though this biologic improvement does not seem to be associated to a control of tumor development. Further studies in patients with less advanced disease are needed to better define the impact of the immune improvement induced by low-dose IL-2 plus β-IFN on the clinical course of the neoplastic disease.
Clinical Significance of Serum Total and Heat-Stable Alkaline Phosphatase in Leukemia Patients
Authors: Patel Prabhudas S. , Adhvaryu Siddharth G. , Baiar Damodar B.
Published: April 2018

Aims and Background

Variations in serum alkaline phosphatase (ALP) and placental-like (heat stable) alkaline phosphatase (PLAP) are found to be clinically useful in cancer patients. The present study evaluated serum ALP and PLAP levels to establish a blood-based biochemical index for leukemia patients.

Study design

ALP and PLAP levels were determined in 145 untreated leukemia patients, 77 anemia patients, 150 healthy individuals (controls), 47 leukemic patients in remission and 23 patients with persistent leukemic activity/accelerated leukemic phase (P. Leu./A. Leu.). The enzymes were estimated with highly specific spectrophotometric methods.

Results

Serum ALP and PLAP levels were significantly elevated in anemia patients and leukemia patients compared to controls. Comparison between anemia patients and leukemia patients showed insignificant differences for ALP, whereas PLAP levels were significantly raised (p < 0.001) in leukemia patients. ALP showed insignificant difference between untreated leukemia patients, patients with P. Leu./A. Leu. and leukemia patients in remission. PLAP levels were comparable in patients with P. Leu./A. Leu. and were significantly lower (p < 0.02) in leukemia patients in remission than in untreated leukemia patients.

Conclusions

The results indicate that serum PLAP levels are a useful biochemical marker for diagnosis and treatment monitoring of leukemia patients. However, serum ALP levels have limited utility for leukemia patients.
Ultrasoundguided Fineneedle Aspiration of Impalpable Breast Nodules
Authors: Barbano Pier Remigio , Reali Gaetano
Published: April 2018

Aims

This study was designed in an attempt to improve the sensitivity of cytologic examination of fineneedle aspiration biopsies.

Methods and Results

A prospective study was carried out on 79 patients with breast lesions less than 1 cm in diameter and clinically impalpable who were referred to the Radiodiagnostics Section of the Ca’ Granda Hospital of Milan in 1990 and 1991 for mammographic and ultrasound verification. The examination was carried out using a high frequency (10 MHz) ultrasound probe to which an aspiration needle had been soldered. This made it possible to quickly and accurately reach the target nodule and thus gave a high sensitivity of the examination (93 %). However, attachment of the needle to the probe prevented sampling from other points of the nodule and was responsible for the slight Increase in number of inadequate samplesfi which in turn worsened the specificity of the test (86 %). To check the gold standard of the examination, all the patients with positive or doubtful aspirations underwent surgical biopsy, whereas strict radiologic controls were performed in the negative cases.

Conclusions

Ultrasound-guided fineneedle aspiration may have advantages over needle aspiration performed with the stereotactic radiologic technique. The needle can be monitored even if the patient moves; even deep, peripheral nodules as well as those near a prosthesis can be reached; repeated samples can be taken, and costs are limited.
Reversal of Methotrexate-Induced Folate Pool Depletion by Thymidine in a Human Leukemia Cell Line in Vitro
Authors: Sur Pratima , Matsuo Yoshinobu , Otanl Takeshi , Minowada Jun
Published: April 2018

In an In vitro study using a human monocytic leukemia cell line, U-937, the effects of interferon-γ (IFN-γ) in combination with the antifolate methotrexate and the role of thymidine introduced as a biochemical modulator were investigated. Methotrexate alone or in combination with INF-γ was found to enhance the induction of morphologic and functional monocytic differentiation in the U-937 cell line. Various cellular effects with the addition of thymidine to the medium with methotrexate and IFN-γ were studied. Enhanced inhibition of cell growth and perturbation of the cell cycle were noted when methotrexate and IFN-γ were used in combination, but not when methotrexate was used alone. The reduction of cellular folate by methotrexate was also enhanced in combination with IFN-γ. Cell cycle delay, resulting in cell growth inhibition of folate depletion, caused the induction of differentiation in U-937 cells, which was found to be greater with methotrexate + IFN-γ than with methotrexate alone. Cellular differentiation, as assessed by nitroblue tetrazolium reduction assay, indirect immunofluorescence and morphology, showed better effects towards the differentiation of U-937 cells when the agents were used in combination. However, addition of thymidine to the medium was found to cancel all the aforementioned effects. The addition of thymidine to the medium also caused reversal of the inhibitory effect of methotrexate and IFN-γ on cell growth and repletion of the endogenous folate level. Repletion of the folate level by exogenous thymidine is a new possibility for the role of the thymidine in cellular growth.
Down Regulation of Qa Gene Expression on Drug-Modified Tumor Cells
Authors: Leroy Elisabeth , Lattuada Donatella , Casnicl Claudia , Franco Paola , Marelli Ornella E.A.
Published: April 2018

Background

Mouse leukemia, L1210, strongly enhances its immunogenicity following in vivo treatment with 5-(3-3′-dimethyl-1-triazeno) imidazole-4-carboxamide (DTIC). Previous experiments have shown that transformed cells elicit a cell-mediated response accountable for rejection and resistance to a subsequent injection of parental tumor into a syngeneic host. L1210 expresses classical H-2 class I molecules, and since it has been shown that DTIC treatment does not modify the expression of these molecules, this is a suitable model to study nonclassical class I antigens, such as Qa2 glycoproteins, and their potential role in tumoregenicity.

Methods

Cloned cells from L1210 were treated with DTIC and then H-2D, and Qa antigen expression was studied on four clones, before and after xenogenization with DTIC.

Results and conclusions

a strong decrease of Qa2 molecule expression was demonstrated by radioimmunoassay and immunofluorescent staining and was confirmed by FACS and 2D-gel analysis. The presence or the absence of Qa antigens on tumor cells could thus be involved in tolerance or rejection of tumor cells in syngeneic animals.
Urinoma Formation Secondary to Ureteral Obstruction by Metastatic Squamous Cell Carcinoma of the Appendix. Case Report
Authors: Angulo Javier C. , Lopez Jose I. , Lopez-Arregui Eduardo , Flores Nicolas
Published: April 2018

We report a case of secondary squamous cell carcinoma of the appendix causing spontaneous extravasation of urine and urinoma formation. On the basis of clinical findings, we interpret this rare lesion as metastatic from a cervical carcinoma surgically resected 8 years earlier. Ureteral continuity was restored by retrograde catheterization and the urinoma was drained percutaneously. The final diagnosis was made at laparotomy.
Teratoid Wilms’ Tumor. A Unilateral Case
Authors: Kotiloğlu Esin , Kale Gülsev , Sevinir Betül , Hiçsönmez Akgün , Akçören Zuhal
Published: April 2018

A unilateral teratoid Wilms’ tumor in a 3-year-old girl is presented. Histopathologic features of this rare variety, differential diagnosis and effects of chemotherapy are discussed in light of other reports in the literature.
Recent Advances in the Development of Anticancer Drugs that Act against Signalling Pathways
Authors: Powis Garth
Published: April 2018

Cancer can be considered a disease of deranged intracellular signalling. The intracellular signalling pathways that mediate the effects of oncogenes on cell growth and transformation present attractive targets for the development of new classes of drugs for the prevention and treatment of cancer. This is a new approach to developing anticancer drugs and the potential, as well as some of the problems, inherent in the approach are discussed. Anticancer drugs that produce their effects by disrupting signalling pathways are already in clinical trial. Some properties of these drugs, as well as other inhibitors of signalling pathways under development as potential anticancer drugs, are reviewed.
Primary Site as Predictive Factor of Local Control in Advanced Head and Neck Tumors Treated by Concomitant Boost Accelerated Radiotherapy
Authors: Corvò Renzo , Sanguineti Giuseppe , Scala Marco , Garaventa Giacomo , Santelli Alida , Barbieri Marco , Vitale Vito
Published: April 2018

Aims and background

The purpose of this phase II study was to assess the efficacy and toxicity of an accelerated radiotheraphy schedule with the concomitant boost technique in the management of patients with advanced head and neck squamous cell carcinomas (HN-SCC) of various primary sites.

Methods

From May 1989 to December 1992 45 patients were scheduled to receive a total dose of 75 Gy in 40 fractions over 40 days. The boost encompassing the macroscopic disease was given as a second daily dose during the last 2 weeks of the basic treatment.

Results

Severe mucositis was recorded in 27 (60%) patients. Late side effect occurred in 2. As regards local control the primary tumor site was the most significant prognostic factor: at a median follow-up of 24 months (range 12-52 months) the actuarial local control rate was 79%, 48% and 15% for oronasopharyngeal, laryngohypopharyngeal and oral cavity primary sites, respectively (p=0.004).

Conclusions

This high dose concomitant boost regimen appears feasible in advanced HN-SCC. However, our results indicate the primary tumor site as a major prognostic factor even with an accelerated treatment schedule.
First Recurrence Analysis of 840 Cutaneous Melanomas: A Proposal for a Follow-Up Schedule
Authors: Martini Laura , Brandani Paola , Chiarugi Cristina , Reali Umberto M.
Published: April 2018

Aims and background

A correct follow-up schedule for patients who underwent an excision for stage I cutaneous melanoma might allow the early detection of local and distant metastases. At present, there is no general agreement on follow-up protocols. In order to work out a follow-up guide, we have retrospectively evaluated the records of 840 stage I cutaneous melanoma patients surgically treated and followed during the postoperative period in the Division of Plastic Surgery of the University of Florence from 1975 to 1992.

Methods

We evaluated the patients’ records by analyzing time, pathway and site of any first recurrence in relation to the main prognostic factors such as patient sex, site, histological type and depth of invasion of each primary melanoma. A statistical analysis was performed.

Results

To summarize, the salient results were the following: 80% of relapses occurred in the first 3 years and they occurred significantly earlier when the primary melanoma was localized in the trunk and significantly later when the melanoma was localized in the lower limbs and for < 1.5 mm lesions. The first recurrence occurred earlier by the lymphatic than by the hematic pathway regarding the overall number of patients. The hematic pathway was the most frequent (with respect to the overall percentage of hematic metastases) for the melanomas localized in the head and neck region and for lentigo malignant melanomas, whereas the lymphatic pathway was most frequent for melanomas of the lower limbs and > 3 mm in thickness.

Conclusions

We suggest a follow-up schedule taking into consideration the postoperative behavior of stage I cutaneous melanoma patients (in terms of time and pathway of the first recurrence) in relation to the site and depth of invasion of the tumor.
Granular Cell Tumor: An Immunohistochemical Study
Authors: Cavaliere Antonio , Sidoni Angelo , Ferri Ivana , Falini Brunangelo
Published: April 2018

Aims and background

Granular cell tumor, usually a benign neoplasm, has been the object of many studies because of its uncertain histogenesis and based on many immunohistochemical and ultrastructural studies it has been suggested that it originates from the Schwann cell. Our recent observation that granular cell tumor is positive with PG-M1, a new anti-macrophage monoclonal antibody, led us to further investigate the immunophenotypic profile of the tumor.

Study design

We studied 11 granular cell tumors using a panel of 20 antibodies, 13 monoclonal and 7 polyclonal.

Results

The immunohistochemical study showed in all cases a constant diffuse positivity for S-100 protein, neuron-specific enolase, vimentin, KP1 and PG-M1, as well as occasional and focal positivity for alpha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme.

Conclusions

The immunophenotypic profile constantly observed could be the expression, on one hand, of the neuroectodermic nature of the neoplasm, proven by positivity for S-100 protein, neuron specific enolase and vimentin, and on the other could be the expression of the phagocytic activity of the tumor cell, proven by positivity for KP1 and PG-M1 antibodies and also by the presence of numerous phagolysosomes.
Smooth Muscle Tumors of the Breast: Clinicopathologic Features of Two Cases
Authors: Boscaino Amedeo , Ferrara Gerardo , Orabona Pasquale , Donofrio Vittoria , Staibano Stefania , De Rosa Gaetano
Published: April 2018

Two cases of smooth muscle tumor of the breast with high tendency to local relapses are reported. The common cytohistologic feature of these infrequent neoplasms is interfacing bundles with spindle-shaped cells showing eosinophilic cytoplasm and blunt-ended nuclei. In estimating the prognosis of these lesions, the mitotic index must be evaluated together with evidence of necrosis and hypercellularity. The present cases suggest that, in the absence of the ancillary features, a mitotic rate of 1-3 × 10 HPF might define a “grey zone” in the spectrum of lesions between leiomyomas and leiomyosarcomas: the smooth muscle tumors of indeterminate prognosis (low risk lesions).
Mortality from Skin Melanoma in Italy and Friuli-Venezia Giulia Region, 1970-1989
Authors: Franceschi Silvia , Bidoli Ettore , Prati Sabrina , Fascioli Silvia , La Vecchia Carlo
Published: April 2018

Aims and background

Substantial upward trends for skin cancer mortality have been observed in most European countries in the last two decades. The distinction, however, between cutaneous malignant melanoma (CMM) and non-melanomatous skin cancers on the basis of death certification is unreliable

Methods

In order to assess the trends of CMM, analysis of the specific code for CMM (International Classification of Disease VIII and IX:172) was coupled with analysis of total skin cancer mortality rates, standardized on the 1981 Italian Census population, at all ages and in selected age groups (15-44, 45-64 and 65-84 years). The analyses were carried out for the whole of Italy and for Friuli-Venezia Giulia (FVG), a region in North-East Italy with a high proportion of fair-complexioned individuals, elevated frequency of sunbathing, and especially good diagnostic standards.

Results

In 1985-89 skin cancer mortality rates in men at all ages, as compared to 1970-74, were 33% higher in Italy and 46% higher in FVG. In women, there was a rise of 22% in Italy and 94% in FVG. More marked upward trends were observed in young and middle aged adults, especially among women in FVG (over 300% increase). In absolute terms, approximately 3000 more Italians died from skin cancers in 1985-89 as compared to 1970-74, about half of them prematurely (i.e., < 65 years). CMM was mentioned in death certifications for skin cancer increasingly often in all age groups, particularly in FVG.

Conclusions

The analysis of mortality trends from skin cancer is consistent with a substantial rise of CMM-related deaths. The sensitivity of death certification with respect to CMM diagnosis is also increasing, especially in FVG. A public health strategy with the aim of reducing intermittent intense exposure to ultraviolet light, especially in children, is urgent in Italy as CMM represents one of the few causes of premature death with unfavorable trends.
Volunteers in Hospital and Home Care: A Precious Resource
Authors: Fusco-Karmann Claude , Tamburini Marcello
Published: April 2018

Aims and background

Ten years ago, a program o intervention by volunteers in cancer hospitals and at home was started. Home care is accomplished by teams of palliative care givers, in which volunteers are included. After a selective interview, all voluntary candidates with the necessary qualifications are trained and specific apprenticeship is done. Hence, their professional training is carried out through regular groups of supervision followed by a psychologist and a coordinator. A study was carried out to evaluate the activity of volunteers, in the hospital and at home, as judged by patients, nurses and the volunteers themselves.

Methods

On the whole, the data analyzed concerned 216 patients, 163 nurses and 92 volunteers in the hospital and 30 patients, 16 nurses and 35 volunteers at home. The questionnaires used for the study had four possible answers (no, a little, much, very much) or required an answer on a scale of 0 to 10.

Results

A high quota of patients gave a very positive opinion (“much” or “very much”) on the importance of the presence of volunteers in the hospital (76%) and at home (90%). In the second case, volunteers were particularly useful to improve a patient's mood (80%) and to solve practical problems (47%). General agreement was noted among nurses and volunteers on the activity of the latter. The main form of intervention of all volunteers is to give psychosocial support to patients. A score of 7 to 10 was given to this item by 60% of the nurses and by 82% of the hospital volunteers. At home, respectively 80% and 89% gave such a score for the same item. Other activities of the volunteer were support for the family, assistance in social activities, and to give information.

Conclusions

The presence of the volunteer in the hospital and at home appears to be helpful to the patient and the family by becoming part of the team without becoming involved directly in its clinical activity.
Growth Inhibition of Human Endothelial Cells by Human Recombinant Tumor Necrosis Factor Alpha and Interferon-Gamma
Authors: Mauerhoff Thekla , Belfiore Antonino , Pujol-Borrell Ricardo , Bottazzo Gian Franco
Published: April 2018

We investigated the effect of recombinant tumor necrosis factor-alpha (rTNF- α) on the proliferative response of human umbilical vein endothelial cells (HUVEC) to normal human serum (NHS), in the absence or the presence of interferon (IFN)- γ. rTNF- α significantly impaired NHS-stimulated HUVEC growth at a dose as low as 0.1 U/ml. The inhibitory effect of rTNF- α was dose-dependent up to 50-100 U/ml and was already evident after 2 h of incubation. Doses of rTNF- α in the range of 10 U/ml completely suppressed 3H-thymidine uptake stimulated by 7.5% NHS, and the effect was partially overcome by 10-20% NHS. rTNF- α was not cytotoxic at doses up to 1000 U/ml. rIFN- γ was also effective in suppressing NHS-stimulated3H-thymidine incorporation, and at low doses (0.1 U/ml) rIFN- γ and rTFN- α showed an additive effect. The effect of TFN- α and IFN- γ in antagonizing the proliferative response of vascular endothelium to the variety of growth factors contained in human serum could be relevant in a variety of pathologic conditions involving endothelium damage and proliferation.
Medical Treatment of Hepatocellular Carcinoma: Any Progress?
Authors: Colleoni Marco , Gaion Fernando , Liessi Guido , Mastropasqua Giorgio , Nelli Patrizia , Manente Paolo
Published: April 2018

Background

Hepatocellular carcinoma (HCC) remains one of the most common neoplasms worldwide. Curative treatment options include liver transplantation or resection. Unfortunately, most patients still have unresectable or untransplantable HCC due to disease extension or comorbid factors and are therefore candidate only for palliative treatments.

Methods

In this review we have analyzed the different medical approaches employed in the treatment of HCC in an attempt to better define their roles.

Results

Palliative medical treatments including systemic chemotherapy, immunotherapy or hormonal manipulation rarely influence survival of the patients. Although a high response rate is often reported with new local therapies such as transcatheter arterial embolization, intraarterial chemotherapy or percutaneous ethanol injection, the real impact of these treatment modalities on patient survival remains to be determined.

Conclusion

One way to improve the diagnosis of HCC patients would be an appropriate approach to evaluate new drugs or treatment modalities. To answer all the open questions, further trials, possibly randomized, should be conducted on a substantial number of patients with homogeneous prognostic factors.
A Pilot Clinical Trial of Surgical Adjuvant Treatment with High-Dose 6S-Leucovorin/5-Fluorouracil and Radiation Therapy for High-Risk Rectal Carcinoma
Authors: Cascinu Stefano , Veraldi Antonio , Foglietti Gian Paolo , Ghiselli Roberto , Saba Vittorio , Lungarotti Ferdinando , Babini Lucio , Catalano Giuseppina
Published: April 2018

Aims and background

The study was performed to evaluate the feasibility of combining leucovorin (LV) with 5-fluorouracil (5FU) and radiation therapy as adjuvant treatment for high-risk rectal carcinoma.

Methods

Twenty-five patients with histologically proven adenocarcinoma of the rectum, at high-risk of recurrence after potentially curative resection (T3 NO, T any N1-2; MO), received 5FU (370 mg/m2) and 6S-LV (100 mg/m2) on days 1-5, 4 and 8 weeks after surgery. On treatment day 64, radiotherapy on the pelvis (50 Gy) was initiated. Finally, three further courses of 5FU/LV were given at intervals of 4 weeks beginning 28 days after the completion of radiotherapy.

Results

The treatment was generally well tolerated. We observed only 2 cases of grade III toxicity (diarrhea) during the third cycle of chemotherapy. No severe complications were recorded following the use of radiotherapy. The mean overall 5FU dose intensity was 92%. After a median follow-up of 24 months, 4 patients had relapsed (liver, lung, and pelvis, 2 cases).

Conclusions

The association of LV to 5FU and radiation therapy seems to be feasible, with acceptable toxicity. The advantage of this combination, in terms of recurrence rate and survival with respect to 5FU/radiotherapy alone, will have to be evaluated in randomized trials.
Radiation Therapy of Spinal Metastases: Results with Different Fractionations
Authors: Tombolini Vincenzo , Zurlo Alfredo , Montagna Antonietta , Notarianni Ermanno , Osti Mattia Falchette , Enrici Riccardo Maurizi , Pirolli Carlo
Published: April 2018

Aims and background

Local radiotherapy plays an important role in the palliative treatment of all skeletal metastases, particularly those of the spine, with the purpose to obtain pain relief and prevent pathologic fractures or vertebral collapse.

Methods

From June 1991 to October 1993, 95 patients with a total of 103 sites of spinal metastases were treated at the Institute of Radiology of the University of Rome “La Sapienza”. Fractionations and total doses were divided as single fractions of 800 cGy, hypofractionated multiple fractions for a total dose of 20 Gy administered in 4-5 days, and conventional multiple fractions for a total dose of 30-40 Gy in 2-4 weeks. An evaluation of the efficacy of the different radiation treatments was performed with the use of a simplified descriptive pain scale.

Results

Seventy-three (70.9%) of 103 treatments were evaluables. An overall response rate of 82.2% was obtained: complete in 38.3% and partial in 43.8%, irrespective of total dose, fractionation and location of irradiated spinal metameres. The analysis of results did not show significant differences between the treatment courses.

Conclusions

We confirm that radiation therapy has a major role in the management of pain control and prevention of fractures in patients with spinal metastases. Hypofractionated and single fraction treatments showed equal efficacy compared to more prolonged therapy, with an advantage for the patient and the radiation therapy institution.
Congenital-Infantile Fibrosarcoma: Study of Two Cases and Review of the Literature
Authors: Corsi Alessandro , Boidrini Renata , Bosnian Cesare
Published: April 2018

Background

Congenital-infantile fibrosarcoma is a rare tumor of the pediatric age. It involves subjects under 5 years of age, and more than 200 cases have been reported in the literature.

Methods

The authors present the clinicopathologic findings of 2 cases and review the literature.

Results

Of our 2 patients, the first was a 2-years and 6-months-old female and the second a newborn male. The female presented a tumor in the retroperitoneum without recurrences or metastasis after 17 months, and the male on left foor with a recurrence after 3 months. Histologically, the tumors were mainly composed of spindle-shaped cells. Immunohistochemically, in both cases, neoplastic cells were positive for vimentin; focal positivity for muscular specific actin was present in the tumor of the female. Ultrastructurally, tumors were composed of mesenchymal cells with fibroblastic and myofibroblastic features. Flow cytometric analysis of the retroperitoneal tumor showed an aneuploid population of neoplastic cells.

Conclusions

Congenital-infantile fibrosarcoma should be considered a borderline tumor; its biologic behavior is better than that of adult fibrosarcoma. Histologic diagnosis is not easy; the microscopic picture may be confused with fibromatosis or with malignant mesenchymal neoplasms. Only a follow-up of many years can confirm the benignancy or malignancy of any individual tumor, even though clinico-pathologic features may be distinctive enough to permit its recognition.
Role of Granulocyte Colony-Stimulating Factor in Relapsed/Resistant Intermediate and High-Grade Non-Hodgkin's Lymphoma Patients Treated with the E-Shap Regimen
Authors: Mangiagalli Monica , Miccolis Isabella , Maffé Pierfranco , Pogliani Enrico Maria , Corneo Gianmarco
Published: April 2018

Aims and background

The study assessed the role and potential benefit of rhG-CSF in reducing the frequency, duration and severity of neutropenia following cytotoxic chemotherapy according to the E-SHAP protocol and, at the same time in improving the response rate.

Methods

Twenty patients with resistant/relapsed intermediate or high-grade non-Hodgkin's lymphoma were treated with the E-SHAP regimen (etoposide + methyl prednisolone + high dose cytosine arabinoside and cisplatin), and in 15 of them, we administered rhG-CSF between chemotherapeutic courses.

Results

The 15 patients who received G-CSF after E-SHAP were neutropenic for a short time and experienced no febrile episodes or infective complications. In contrast, in the group (5 patients) who did not receive G-CSF, the WBC nadir was lower and the number of days with a neutrophil count below 1.0 × 109/L was longer, with a greater risk of inferctious complications. Of the 15 patients, only one had a delay in chemotherapy administration, and the RDI was 95% in the 65% of patients who received G-CSF. Of 5 patients treated with chemotherapy alone, 4 had a delay and the RDI was over 95% in only one patient. We obtained a good overall response rate (70%) in the group who received G-CSF. In the historical group of 5 non-Hodgkin lymphoma patients, we observed only 1 partial response and 4 had progression of disease.

Conclusions

Administration of G-CSF is associated with an acceleration of neutrophil recovery, indicating its potential to reduce the risk of infection. The use of G-CSF permitted us to administer intensive chemotherapy without delay and according to standard dosage, with an improved response rate.
The Feasibility of Repetitive Courses of High-Dose Continuous Intravenous Infusion Interleukin-2 and Subcutaneous Alpha-Interferon with Polychemotherapy in Advanced Malignant Melanoma
Authors: Foppoli Marco , Citterio Giovanni , Polastri Daniela , Guerrieri Rossella
Published: April 2018

Aims and background

A Phase I study of repetitive courses of chemotherapy (carmustine, cis-platinum, dacarbazine) and immunotherapy (continuous intravenous infusion recombinant interleukin-2 (rIL-2) and subcutaneous (sc) alpha-interferon 2b) plus tamoxifen was performed in order to establish a more efficaciuous way to sequence this kind of treatment for advanced malignant melanoma.

Study design

Patients who had measurable metastatic melanoma, a Karnofsky performance status ≥ 80, and no clinically significant hematologic or cardiac disfunction were considered eligible. Treatment consisted of BCNU, 150 mg/m2 i.v. day 1 in alternating cycles; DTIC, 220 mg/m2 i.v. days 1, 2 and 3; CDDP, 25 mg/m2 i.v. days 1, 2 and 3; tamoxifen 10 mg twice/day per os continuously; rIL-2, 18 × 106 IU/m2/day continuous i.v. infusion days 5-8 (96 h) and days 19-22 (96 h); alpha-interferon (IFN) s.c. 3 × 106 U day 12, 6 × 106 U day 14, 9 × 106 U days 16, 19, 21, 23, 26, and 28 (from cycle 2, 9 × 106 U days 2, 5, 7, 9, 12, 14, 16, 19, 21, 23, 26, and 28). Two consecutive cycles were planned until response evaluation.

Results

Three patients were treated according with the protocol; none of them was able to respect the planned dose-intensity schedule. The given dose intensity/planned dose intensity ratios were as follows: DTIC, 0.74 (range, 0.70-0.80); CDDP, 0.77 (0.72-0.80); BCNU, 0.77 (0.72-0.80); rIL-2, 0.65 (0.36-0.80); alpha-IFN, 0.01 (0-0.03); tamoxifen, 1.0. Systemic side effects of rIL-2 and myelotoxicity were the main reasons for treatment delay and/or dose-reduction, and for the long period of hospital care.

Conclusions

We conclude that the treatment schedule is not feasible. However, since we believe that combined chemo-immunotherapy is a potentially active treatment in metastatic malignant melanoma, we have modified it in order to make it more feasible and consequently efficacious.
Efficacy and Toxicity of Vinorelbine-Carboplatin Combination in the Treatment of Advanced Adenocarcinoma or Large-Cell Carcinoma of the Lung
Authors: Masotti Alessandro , Borzellino Giuseppe , Zannini Guido , Laterza Ernesto , Ricci Francesco , Morandini Giancarlo
Published: April 2018

Aims and background

The aim of the study was to assess the activity and toxicity of the vinorelbine-carboplatin combination in advanced adenocarcinoma or large-cell carcinoma of the lung. The new vinca derivative, vinorelbine, shows promising activity when combined with cisplatin, but toxicity of the combination is substantial.

Methods

Accordingly, we substituted carboplatin for cisplatin in the combination in order to improve the therapeutic index. From March 1992 to March 1994, 55 untreated patients with undifferentiated unresectable or metastatic adenocarcinoma or large-cell carcinoma of the lung were recruited. The treatment consisted of a course of carboplatin (300 mg/m2) and vinorelbine (25 mg/m2) repeated every 4 weeks. The only grade 3 toxicity observed was 16 cases of grade 3 vomiting and 2 cases of grade 3 stomatitis.

Results

The positive response rate was 40% (partial response, 22 patients). In conclusion, the vinorelbine-carboplatin combination may be regarded as an active, safe regimen for the palliative treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.
Immunoglobulin Heavy Chain Gene Rearrangement in B-Cell Non-Hodgkin's Lymphomas Detected by the Polymerase Chain Reaction
Authors: Alaibac Mauro , Paradiso Angelo , Giannella Caterina , Labriola Angela , Marzullo Francesco , Lorusso Vito , De Lena Mario
Published: April 2018

Aims and background

Immunoglobulin heavy chain gene rearrangement serves as a marker of clonality and cell lineage in B-cell lymphoproliferative disorders. In this study we used the polymerase chain reaction (PCR) to detect clonal rearrangements of the immunoglobulin heavy chain gene in a group of patients with B-cell lymphomas.

Methods

DNA was extracted from frozen tissue of 40 B-cell non-Hodgkin's lymphomas and subjected to PCR amplification using primers that recognize conserved sequences of the variable and joining regions of the immunoglobulin heavy chain gene.

Results

Monoclonal rearrangements were detected in 23 of 40 malignant B-cell lymphomas. No clonal rearrangements were detected in the 10 control cases.

Conclusions

We conclude that this PCR-based technique may provide a simplified and rapid approach for the detection of clonal immunoglobulin heavy chain gene rearrangements in B-cell lymphomas without recourse to Southern blotting, which can be reserved for cases in which PCR is negative.
Time Trends in Survival of Children with Acute Lymphocytic Leukemia in Piedmont, Italy: A Report from the Population-Based Cancer Registry
Authors: Magnani Corrado , Pazè Enrica , Terracini Benedetto , Pastore Guido , Mosso Maria Luisa
Published: April 2018

Aims and Background

The Childhood Cancer Registry of Piedmont (RTI) periodically updates the life status of each registered child. Given its size, the RTI is the major (albeit geographically limited) Italian source of population-based survival rates of cancer in children. The present report describes time trends in survival of children with acute lymphocytic leukemia (ALL).

Methods

During 1970-87, 429 residents in Piedmont aged 0-14 were diagnosed as having ALL: they have been followed up until 1991.

Results

Five-year survival rates increased from 21% to 72% for children diagnosed ALL respectively in 1970-72 and 1985-87. Major improvements occurred up to the mid-seventies and again between cases diagnosed in the early and late eighties. Improvement in survival was statistically significant for children belonging to classes comprised between 2 and 10 years of age at diagnosis. Period of diagnosis was unrelated to probability of survival among the 13 cases diagnosed ALL at age 0. Survival was unrelated to sex, even in the early seventies and even after consideration of children dying more than 5 years after diagnosis. Between 1976-81 and 1982-87, an improvement in survival was found in all categories of WBC count at diagnosis: the ratio between the two estimates was somewhat higher for children with more than 50,000 WBC/mm3 at diagnosis than for other children.

Conclusions

Present data are compared with those resulting from other population-based series: this exercise can be useful for an overall evaluation of delivery of cancer therapy at the population basis.