bluuebunny/crossref_metadata_2025 huggingface dataset:
Thyroid Metastases from a Ductal Carcinoma of the Breast. A Case Report
Authors: Ferrara Gerardo , Ianniello Giovanni Pietro , Nappi Oscar
Published: April 2018

A case of bilateral thyroid metastases from ductal carcinoma of the breast is presented with emphasis on some unusual clinical findings: presentation after a long disease-free interval; clinical signs mimicking an acute thyroiditis; cystic structure of the left-sided metastatic nodule. Fine needle aspiration cytology from both nodules showed highly atypical tumor cells, such as to warrant a differential diagnosis between metastatic breast cancer on the one hand and anaplastic and medullary carcinoma of the thyroid on the other. Immunophenotypic study of the neoplasm on a cell block preparation of the aspirated material showed negativity for both thyroglobulin and calcitonin; instead, the tumor cells were strongly stained with antibodies against the “breast-related” markers alpha-lactalbumin and gross cystic disease fluid protein-15. Therefore, immunochemistry allowed us to establish a definite diagnosis of metastatic breast disease of the thyroid, thereby avoiding surgical procedures.
Melanoma of the External Ear
Authors: Bono Aldo , Bartoli Cesare , Maurichi Andrea , Moglia Daniele , Tragni Gabrina
Published: April 2018

Aims and background

Melanoma of the external ear is a rare disease, and its management is controversial. To address this problem, we reviewed the data concerning the patients observed at our Institution.

Methods

We retrospectively reviewed the clinical records of the 20 patients bearing primary ear melanoma observed over a period of about 20 years at the Istituto Nazionale Tumori of Milan.

Results

Initial evaluation of the patients revealed 7 stage I, 12 stage II and 1 stage III. The thickness of the tumors varied from 0.39 to 6.62 mm. Fourteen patients underwent a wedge resection of the skin and cartilage with primary closure, and 6 patients had a partial amputation of the ear. In 8 cases the section was performed at about 1 cm from the border of the tumor, in 6 cases at about 0.5 cm, and in 6 cases at more than 1 cm. The average follow-up was 57 months (range, 1-18 years). Since there was no local recurrence, it could not be related to type and extent of the local resection performed. In contrast, the development of metastases was related to tumor thickness.

Conclusions

A conservative excision with margins of 1 cm can be a safe procedure for invasive ear melanoma, irrespective of tumor thickness. Like melanomas of other sites, the prognosis is linked to the thickness of the tumor.
A Dose-Finding Study of Ifosfamide by Three-Day Continuous Infusion in Pretreated, Advanced Breast Cancer Patients
Authors: Michelotti Andrea , Salvadori Barbara , Donati Sara , Tognoni Alessandra , Tibaldi Carmelo , Conte Pier Franco
Published: April 2018

The purpose of the study was to establish the maximum tolerated dose of ifosfamide, administered over 72 hr, in metastatic breast cancer patients, pretreated with chemotherapy. Ifosfamide and mesna were given at the same dose, in the same solution, using a portable Pharmacia CADD-1 pump connected to a central venous access, at three dose levels: 7.5 g/m2 (6 patients), 9 g/m2 (8 patients), 10.5 g/m2 (3 patients); the courses were repeated every 3 weeks. Seventeen patients with a median age of 55 years (range, 34-68) and median performance status of 0 (range, 0-2) were treated. The patients were pretreated with a median of 2 (range, 1-3) prior regimens including anthracyclines in 14 patients and paclitaxel in 9. Dose-limiting toxicity was defined as the occurrence of any of the following events in ≥ 2/6 patients: absolute neutrophil count <500/ml for >7 days or <100/ml for >3 days; febrile neutropenia; grade 4 thrombocytopenia; any grade ≥ 3 nonhematologic toxicity. The dose-limiting toxicities were febrile neutropenia and grade 4 thrombocytopenia in 2/3 patients treated at 10.5 g/m2. Seven patients achieved an objective response (response rate 41%; 95% CI, 18% to 67%). We conclude that 72-hr infusion of ifosfamide is feasible in ambulatory patients. The recommended dose for phase II studies is 9 g/m2, with courses repeated every 21 days.
A Randomized Trial of Chemotherapy with or without Estrogenic Recruitment in Locally Advanced Breast Cancer
Authors: Baldini Editta , Gardin Giovanni , Giannessi Piergiorgio , Brema Fulvio , Camorriano Alessandra , Carnino Flavio , Naso Cinzia , Pastorino Giuliana , Pronzato Paolo , Rosso Riccardo , Rubagotti Alessandra , Torretta Giorgio , Conte Pier Franco
Published: April 2018

The present phase III trial was carried out to verify whether a kinetic recruitment induced by low doses of diethylstilbes-trol (DES) could increase the killing efficacy of chemotherapy in patients with locally advanced breast cancer. One-hundred and seventeen untreated patients with locally advanced breast cancer (stage IIIA/IIIB) were randomized to receive 3 courses of primary chemotherapy consisting of cyclophosphamide (600 mg/m2 i.v.), doxorubicin (50 mg/m2 i.v.) and fluorouracil (600 mg/m2 i.v.) (CAF) on day 1, or DES-CAF (DES, 1 mg orally days 1-3, CAF on day 4). The courses were repeated every 3 weeks. The patients who achieved an objective response were submitted to mastectomy followed by 3 courses of CAF alternated with 3 courses of CMF (cyclophosphamide, 600 mg/m2 i.v.; methotrexate, 40 mg/m2 i.v.; fluorouracil, 600 mg/m2 i.v.), with or without DES. The two treatment arms were well balanced in terms of clinical and pathologic features. There was no significant difference in response rates to induction chemotherapy between the two treatment arms (objective response rate, 63.3% for CAF and 56.1% for DES-CAF). Median overall survival was 49 and 47 months and median progression-free survival was 24 and 21 months for CAF and DES-CAF patients, respectively. Toxicity was not significantly different in the two groups, with the exception of leukopenia: DES chemotherapy was significantly more myelotoxic than the standard treatment, which resulted in a significant reduction in the actual dose intensity. In spite of the attractive experimental evidence, we conclude that so far there is no clinical advantage in the combination of estrogen and chemotherapy. Further research is needed to investigate different schedules of chemotherapy and hor-mones, or to test the possibility of combining various mitogens.
Mitomycin C and Vinorelbine in Pretreated Breast Cancer
Authors: Colleoni Marco , Manente Paolo , Stocker Joan , Amor Herbert , Lamon Stefano , Nelli Patrizia , Vicario Giovanni , Sgarbossa Gigliola , Graiff Claudio
Published: April 2018

Aims and background

Vinorelbine, a new semi-synthetic vinca alkaloid, has demonstrated high activity as a single agent in pretreated metastatic breast cancer.

Patients and methods

To evaluate the activity of the combination vinorelbine-mitomycin C and to reduce the incidence of side effects, in particular myelotoxicity, patients with metastatic breast cancer pretreated with 1 or more chemotherapy regimens for metastatic disease were treated according to the following schedule: mitomycin C, 10 mg/m2 day 1, and vinorelbine, 25 mg/m2, days 1, 8 and 15, every 28 days.

Results

Twenty-seven patients were enrolled and were evaluable for activity and side effects. A total of 157 cycles were delivered (median 5 cycles per patient). There were 10 partial remissions (37%; 95% confidence interval 20-59%), 5 instances of stable disease and 12 of disease progression. Grade III-IV toxicity was mostly hematological and included thrombocytopenia (4%) and neutropenia (42%).

Conclusion

Our results indicate that the combination of mitomycin C and vinorelbine has moderate activity in pretreated breast cancer.
Abnormalities in Cell Cycle Control in Cancer and Their Clinical Implications
Authors: Sgambato Alessandro , Flamini Giovanna , Cittadini Achille , Weinstein I. Bernard
Published: April 2018

Recent studies indicate that the functions of several genes that control the cell cycle are altered during the carcinogenic process and that these changes perturb both cell proliferation and genomic stability, thus promoting cell transformation and enhancing the process of tumor progression. The purpose of this paper is to review current information on the role of cyclins and related genes in the control of the mammalian cell cycle, the types of abnormalities in these genes found in human tumors and the possible clinical implications of these findings.
Gallium-67 as a Tumor-seeking Agent in Lymphomas - a Review
Authors: Draisma Annelies , Maffioli Lorenzo , Gasparini Massimo , Savelli Giordano , Pauwels Ernest , Bombardieri Emilio
Published: April 2018

Background

At present 67Ga can be considered one of the most widely used viability radiotracers. There is general consensus in the literature that 67Ga has the highest clinical value in the management of lymphoma patients.

Methods

We critically discuss the role of gallium scintigraphy in lymphoma patients on the basis of the experience of the Nuclear Medicine Division at the National Cancer Institute of Milan.

Results and Conclusions

The sensitivity of gallium scan is very high (80-90%) in the staging and follow-up of Hodgkin's disease, and the method is also of great importance in the follow-up of lymphoma patients. We recommend scintigraphy to study the residual mediastinal mass after treatment. Our experiences during the follow-up of 189 lymphoma patients clearly showed the superior performance of gallium scan compared to MRI in the study of the mediastinal region after treatment. Sensitivity and specificity were both very high (90% and 96.9% vs 88.7% and 89.2%, respectively). Gallium scintigraphy can also be used to study the disease-free interval, posttreatment survival, early signs of recurrence and treatment response times. Comparison of the survival curves of 33 patients with diffuse large cell Non-Hodgkin's lymphoma examined at the National Cancer Institute showed a statistically significant difference (logrank test, P=0.0125) between patients with positive and those with negative gallium scan after 4-6 cycles of chemotherapy.
Interventional Radiology and Radiotherapy for Inoperable Cholangiocarcinoma of the Extrahepatic Bile Ducts
Authors: Milella Marco , Salvetti Monica , Cerrotta Annamaria , Cozzi Guido , Uslenghi Elisabetta , Tavola Anna , Gardani Gianstefano , Severini Aldo
Published: April 2018

Aims and background

To evaluate the effectiveness of external radiation therapy (ERT), alone or combined with endoluminal brachytherapy (BRT), following percutaneous transhepatic biliary drainage (PTBD) in the treatment of patients affected by inoperable cholangiocarcinoma.

Methods & study design

From September 1980 to June 1996, 130 jaundiced patients affected by inoperable cholangiocarcinoma were submitted to PTBD at the Division of Radiology C of the National Cancer Institute of Milan. Nineteen were excluded from the present analysis due to the short survival after PTBD (<30 days). The other 111 patients were divided into three groups according to the following therapy: no further treatment after palliative PTBD in 89 patients (80%, group 1); ERT in 10 patients (9%, group 2); ERT plus BRT in 12 patients (11%, group 3). All the ERT+BRT patients were enrolled after 1990 and were treated with high-energy photon beams followed by en-dobiliary insertion of one or two iridium-192 wires.

Results

Median overall survival among the 111 assessable patients was 126 days; for groups 1, 2 and 3 it was 108, 345 and 428 days, respectively. The patients submitted to radiotherapy (ERT alone or ERT+BRT) were evaluated by radiologic examinations after the end of radiation. In group 2, a partial remission in 3 cases, a progression of disease in 1 case, and no change in 6 cases were observed. Among the patients of group 3, complete remission in 5 and partial remission in 7 patients were achieved. In all the patients achieving complete remission, the PTBD could be removed.

Conclusions

The combination of ERT plus BRT improves survival and quality of life of the patients submitted to PTBD for cholangiocarcinoma. Under the technical point of view, radiation treatment is easy to perform, but much caution is required in defining clinical and planning target volumes. Moreover, drainage during the radiation treatment has to be submitted to a very meticulous surveillance.
Local Impairment of Immunoreactivity in Hiv-infected Women with Hpv-related Squamous Intraepithelial Lesions of the Cervix
Authors: Barberis Massimo C. , Vago Luca , Cecchini Giancarlo , Bramerio Manuela , Banfi Giuseppe , D'Amico Maria , Cannone Maria
Published: April 2018

Aims and background

The aim of this study was to compare the local immune response in two groups of patients with high-grade cervical intraepithelial squamous lesions (SIL): one with HIV infection and the other with HPV infection alone.

Materials and methods

16 conization specimens (8 from HIV-infected and 8 from non-HIV-infected patients) of HPV-related, high-grade SIL were selected. The specimens from non-HIV patients were considered as controls. The total number of Langerhans cells, CD4 and CD8 cells present in 10 field areas (3.120 mm2) was recorded in each case. In HIV patients CD4 and CD8 peripheral counts were performed immediately before surgery.

Results

The CD4/CD8 ratio never exceeded 0.71, whereas the lowest ratio in controls was 0.81: this difference was statistically significant (P=0.0009). The mean number of Langerhans cells was markedly reduced in the high-grade SILs in the HIV patients in comparison with controls (P=0.001). The number of CD4 cells and the CD4/CD8 ratio correlated with the peripheral CD4 count (P=0.001 and 0.02).

Conclusions

In our study a marked local impairment of cervical immunoreactivity was observed, which may play a major role in the progression of these lesions in HIV-infected women.
Benign Breast Surgical Biopsies: Are They Always Justified?
Authors: Ciatto Stefano , Bonardi Rita , Ravaioli Alberto , Canuti Debora , Foglietta Flavia , Modena Stefano , Zanconati Fabrizio , Cressa Cristina , Ferrara Paola , Marrazzo Antonio
Published: April 2018

Aim of the study

To evaluate the indications for open surgical biopsy of breast lesions resulting in a benign histologic report.

Methods

A consecutive series of 754 benign breast biopsies was collected from six Italian centers previously participating in a multicenter study on the benign/malignant biopsy ratio. Histologic diagnosis, diagnostic tests performed, final clinical diagnosis and the indication for surgical biopsy were compared.

Results

Fibrocystic alterations represented the most frequent histologic type (43.2%), followed by fibroadenomas (34.5%). Atypical hyperplasia, phyllode tumors and cancerlike lesions (radial scar, sclerosing adenosis) accounted for a minority of cases. The diagnostic approach was different among centers, with mammography, ultrasonography or cytology being underused in some of them. Suspicion of cancer was an indication for surgical biopsy in 66.7% of cases. In the remaining cases the final report was negative or benign, but biopsy was advised for growing lesions (11.3%) or for cosmetic (3%) or psychological reasons (8.2%). In 4% of cases surgical biopsy was presumably advised for the concurrent influence of high-risk conditions such as previous breast cancer (0.7%), family history of breast cancer (2%) or contralateral synchronous breast cancer (1.3%). In 6.8% of the cases biopsy was advised elsewhere for unknown reasons. The indications for biopsy differed among centers, with one center having a low rate of suspicious cases (37%) and a high rate of reported “cosmetic” or “psychological” reasons (47%).

Conclusions

Leaving aside differences in diagnostic approach and aggressiveness, two thirds of all lesions were biopsied in order to exclude cancer. The routine use of a more complete diagnostic protocol and/or alternative methods to obtain a histologic diagnosis (e.g. core biopsy) might substantially reduce the need for open surgical biopsy.
Treatment of Malignant Gliomas: A New Approach
Authors: Paccapelo Alessandro , Piana Claudio , Rychlicki Franco , Recchioni Maria Antonietta , Salvolini Ugo , Ducati Alessandro , Bonsignori Maurizio
Published: April 2018

The aim of this study is to describe the authors’ experience with intra-arterial ACNU chemotherapy of malignant gliomas. The prognosis of cerebral malignant gliomas remains poor, whatever traditional therapy is applied. ACNU is a well tolerated nitrosourea with a strong antimitotic effect on neurogenic cells both in vitro and in vivo; this drug has enhanced efficacy when used at high concentrations, particularly as an intraarterial infusion. Seventy-six patients have been studied to date, 68 of whom are evaluable; these patients were treated by intraarterial infusion of ACNU (100 mg/m2) every 6 weeks, with a mean of 2.5 courses per patient. The objective response (OR) was 28% and analysis of pretreatment factors revealed that survival was influenced by histological grade, other types of therapy applied, and age. In general IAC is well tolerated and the response and survival appear to be better than with systemic chemotherapy.
Myeloprotective Effect of Early Primary Granulocyte-Colony Stimulating Factor during Six Courses of Intensified 5-Fluorouracil, Epirubicin and Cyclophosphamide (120FEC) Chemotherapy for Advanced Breast Cancer
Authors: Riccardi Alberto , Brugnatelli Silvia , Giordano Monica , Danova Marco , Pugliese Palma , Tinelli Carmine , Klersy Catherine , Richetti Antonella , Fava Sergio , Nastasi Giuseppe , Rinaldi Elena , Fregoni Vittorio , De Monte Andrea , Trotti Giovanni , Bovio Antonella , Ascari Edoardo ,   (Cooperative Group of Study and Treatment of Breast Cancer)
Published: April 2018

Aims and background

The neutropenia induced by six courses of an intensified FEC regimen is expected to be checked by early primary administration of G-CSF which is stopped eight days before the next chemotherapy course. Less information is available about megakaryocytic and erythroid toxicity over six courses.

Methods and study design

Sixty-six consecutive patients with metastatic breast cancer completed six courses of a randomized treatment with two FEC regimens adminstered every 21 days, in which 600 mg/m2 of cyclophosphamide and 5-FU was associated with 60 or 120 mg/m2 of epirubicin (60FEC, 35 patients, vs 120FEC, 31 patients). 120FEC was supported by early primary G-CSF (days 4 to 13). Blood counts were obtained seven times during each course.

Results

The non-hematologic toxicity over 364 courses was similar in 60FEC and 120FEC. No cumulative hematologic toxicity was observed for white blood cells (WBC) and platelets (PLT), while for hemoglobin (Hb) a somewhat higher cumulative toxicity was observed with 120FEC than with 60FEC. WBC, PLT and Hb grade III-IV toxicity occurred in 40.1% and 45.6% (P=ns), in 23.1% and 0.8% (P <.0001) and in 15.6% and 3.0% (P <.005) of the two regimens, respectively. There were no febrile or hemorrhagic episodes. The epirubicin relative dose intensity delivered was 1.95 in 120FEC with respect to 60FEC.

Conclusions

Our G-CSF schedule permitted to deliver six courses of 120FEC without any clinically relevant side effects. Grade III-IV leukopenia was similar with 120FEC and 60FEC, while grade III-IV thrombocytopenia and anemia occurred more often with 120FEC than with 60FEC.
Combined Epirubicin and Interleukin-2 Regimen in the Treatment of Malignant Mesothelioma: A Multicenter Phase II Study of the Italian Group on Rare Tumors
Authors: Bretti Sergio , Berruti Alfredo , Dogliotti Luigi , Castagneto Bruno , Bertulli Rossella , Spadaro Pietro , Toscano Giuseppe , Astorre Paolo , Verusio Claudio , Lionetto Rita , Bruzzi Paolo , Santoro Armando
Published: April 2018

The Italian Group on Rare Tumors undertook a phase II study of a combination of epirubicin and interleukin-2 in 21 chemotherapy-naive patients with malignant mesothelioma. All patients had bidimensionally measurable disease at CT scan. Treatment included intravenous administration of epirubicin at a dose of 110 mg/m2 i.v. on day 1, and interleukin-2 at a dose of 9 MU subcutaneously from day 8 to day 12 and from day 15 to day 19. Cycles were repeated every three weeks, up to six times in the absence of progressive disease. Treatment response was evaluated after two cycles of therapy. Only one patient achieved a partial response, resulting in an overall response rate of 5% (1/21) with a median progression-free and overall survival of 5 and 10 months, respectively. Toxicity was relevant and caused treatment discontinuation in many patients. These results do not support the use of such a combination in the management of malignant mesothelioma.
Limited Role of TP53 and TP53-Related Genes in Myxoid Liposarcoma
Authors: Pilotti Silvana , Lavarino Cinzia , Mezzelani Alessandra , Torre Gabriella Della , Minoletti Fabiola , Sozzi Gabriella , Azzarelli Alberto , Rilke Franco , Pierotti Marco A.
Published: April 2018

Aims

Circumstantial evidence suggests that genetic changes may lead to tumor progression within the myxoid liposarcoma tumors (MLTs) carrying non-random chromosomal translocation t(12;16).

Methods

To address this subject an immunophenotypic analysis, applying antibodies against proteins encoded by TP53, MDM2 and CDK4 genes, complemented by molecular analysis of eight suitable cases, was performed on 104 consecutive cases. Chromosomal translocations were assessed either by cytogenetic analysis or by RT-PCR in 9 suitable cases and chimeric transcripts were found in all cases but two pleomorphic liposarcomas.

Results

Based on immunophenotyping and tumor site, the case material consisted of three groups. The first one was made up of 92 non-retroperitoneal cases carrying a null p53, mdm2, cdk4 immunophenotype, which remained unchanged over the time of recurrences and along the gamut of histologic subtypes. The second group was represented by five p53+, mdm2-, cdk4- non-retroperitoneal cases, 4 of which were further analysed by PCR-SSCP for p53 mutation. The im-munophenotipic profile of these cases, complemented by the molecular findings, supported a role of TP53 in tumor progression in three high-grade MLTs. The third group, consisting of 7 retroperitoneal cases, showed a heterogeneous immunophenotype, sharing immunophenotypic and molecular features with the well-differentiated/evoluted (dedifferentiated) liposarcoma group.

Conclusions

TP53 mutations seem to play a role in tumor progression in a few cases of MLTs (2.8%) showing more aggressive histologic characteristics. The unexpected finding that a number of retroperitoneal LMTs display the immunophenotypic profile of the well differentiated/evoluted (dedifferentiated) liposarcomas, deserves further investigation.
Characterization of a Murine Monoclonal Antibody against Human Esophageal Squamous Cell Carcinoma-Associated Antigen
Authors: Nadkarni Jagdish S. , Bhadsavle Pushpalaxmi R. , Chitnis Vivek S. , Nadkarni Jayshree J. , Vyas Jitendra S. , Desai Praful B.
Published: April 2018

A murine monoclonal antibody (MAb) 2G3 of the lgG1 type was raised using the human esophageal squamous cell carcinoma (SCC) cell line TE-2. Immunoblotting with 2G3 indicated that the antigen recognized by 2G3 has a molecular weight of 34 kD. Its activity was evaluated by immunoperoxidase and immunofluorescence on frozen and paraffin sections of various normal tissues, normal and benign tumors as well as various established cell lines. The pattern of reactivity revealed that the antigen recognized by 2G3 was expressed mainly by esophageal SCC. The only exception was represented by malignant breast tumors, where it reacted weakly. Scatchard analysis using 125I-labelled 2G3 showed that TE-2 has approximately 7.5 times more binding sites than the MCF-7 breast cancer cell line. The use of this new MAb is therefore proposed for the histopathological diagnosis of esophageal SCC.
Ras and C-Myc Oncoproteins during Tumor Progression in the Uterine Cervix
Authors: Nair Sivakumari Asha , Nair Madhavan Balaraman , Jayaprakash Puthuveetil Govindan , Rajalekshmy Thayyullathil Nellika , Nair Madhavan Krishnan , Pillai Madhavan Radhakrishna
Published: April 2018

Aims and background

Altered oncogenic activity is a feature associated with many malignant and premalignant conditions. Among the many oncogenes, ras and myc are commonly altered in many tumors. This study aims to evaluate the expression of ras and c-myc oncoproteins in a total of 204 cervical tissue samples, including premalignant and malignant lesions as well as apparently normal cervical tissue.

Methods and study design

Mouse monoclonal antibodies against the three mammalian ras gene products (c-H-ras, c-K-ras, c-N-ras) and the c-myc protein were used to evaluate oncoprotein expression by immunocytochemistry.

Results

None of the samples analyzed displayed immunoreactivity for H-ras and K-ras. Normal cervical epithelium showed minimal immunoreactivity for N-ras with about 33% of the samples expressing the protein. More conspicuous expression in normal tissue was displayed by c-myc, with about 90% of the samples expressing the protein (mean value of cells positive = 34%). The immunoreactivity for N-ras increased with increasing histological abnormality from low-grade squamous intraepithelial lesions (SIL) to invasive carcinoma. Increased immunoreactivity for N-ras was evident in the basaloid cells of malignant lesions, with the maximum value of 66% found in poorly differentiated squamous cell carcinoma (PDSCC). The percentage of nuclei positive for c-myc also showed a gradual increase from low-grade SIL onwards, the highest positivity being found in PDSCC, where the mean value was 85%. Statistical analysis revealed a good correlation between the expression of N-ras (r = 0.8922, P = 0.001) and c-myc (r = 0.8856, P =0.001) and various histological stages of tumor progression in the cervical epithelium.

Conclusions

These results therefore suggest that c-myc and N-ras oncoproteins are important during tumor progression in the uterine cervix.
Expression of Cell Surface Glycoprotein CD44 and Integrins in Breast Cancers among Indian Women
Authors: Menon Malini M. , Thakur Rashmi , Simha Mangala R. , Kurkure Arun P. , Kenkare Umakant W. , Doctor Vatsala M.
Published: April 2018

Parsis, the sole surviving group of followers of Zoroaster who are settled in Bombay, have a fourfold higher incidence of breast cancer than the general population of Greater Bombay. CD44 expression was studied by immunohistochemistry in breast cancers of 50 non-Parsi and 35 Parsi women, 10 normal breast tissues, 10 proliferative lesions and 49 tissues adjoining a tumor mass. α2 and β1 integrins could be studied in only 42 malignant cases and five normal tissues. The immunohistochemistry results were correlated with other parameters including tumor grade and size, estrogen and progesterone receptor status, lymph node involvement and mitotic index. CD44 was not expressed in normal areas. Benign areas and tissues adjacent to tumor masses showed increased staining. Both Parsi and non-Parsi women showed significantly high CD44 expression. All Parsi ILCs were strongly positive for CD44. In both groups ER negativity was associated with strong CD44 positivity, while mitotic counts correlated with decreased CD44 expression in Parsis but not in non-Par-sis. α2 and β1 integrins were strongly expressed on the baso-lateral surface of normal epithelium. However, they were downregulated in tumors. In general breast tumor tissues from Parsi and non-Parsi patients did not differ significantly with respect to most parameters. However, among Parsis lymph node involvement and CD44 correlated weakly whereas the mitotic index was inversely correlated with CD44. The reverse was true for non-Parsis. The deviation from the general pattern needs further study based on a large number of samples and appropriate use of splice variants.
Second Primary Renal Cell Carcinomas following Solid Tumors. Four Case Reports and Review of the Literature
Authors: Koumarianou Anna A. , Vernon Clare C.
Published: April 2018

We report multiple malignancies in four patients with metachronous renal adenocarcinomas. The group of patients includes two women treated for primary breast and ovarian cancer and two men with prostate and colon cancer respectively. The occurrence of renal cancer following these primary solid tumors was not associated with previous treatments. The authors review the literature and discuss pathogenic mechanisms underlying renal cell carcinoma.
Accessory Breast Cancer: A Case Report and Review of the Japanese Literature
Authors: Hatada Takuya , Ishii Hiromitsu , Sai Katsunari , Ichii Shigetoshi , Okada Kaoru , Utsunomiya Joji
Published: April 2018

The case of a 31-year-old woman with accessory breast cancer in the left axilla is described. She had noticed a swelling in the left axilla during her three pregnancies. The preoperative diagnosis of accessory breast cancer was made on the basis of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) and clinical history. She was treated by wide local resection and regional lymph node dissection. Although cancer originating from accessory breast tissue has been reported very rarely, knowledge of this disorder may facilitate the correct diagnosis of axillary tumors. US-FNAB is a useful and simple technique for the tissue diagnosis of axillary tumors.
Splenic Mucinous Cystadenocarcinoma Arising in Heterotopic Pancreatic Tissue
Authors: Zanetti Gianfranco , Riccioni Luca , Gallo Carmine , Salfi Nunzio , Martinelli Giuseppe Nicola
Published: April 2018

A mucinous cystadenocarcinoma along with remnants of normal pancreatic tissue was discovered in the spleen of a 21-year-old woman. Extensive clinical, radiological, ultrasound and computed tomography investigation revealed that the patient's pancreas and ovaries were unremarkable. We presume an origin from heterotopic pancreatic tissue for this neoplasm and present a review of the literature in this regard.
Does the Information Level of Cancer Patients Correlate with Quality of Life? A Prospective Study
Authors: Annunziata Maria Antonietta , Foladore Silva , Magri Maria Donatella , Crivellari Diana , Feltrin Alessandra , Bidoli Ettore , Veronesi Andrea ,   Within the framework of the North-Eastern Italian Oncology Group
Published: April 2018

Aims and background

The aim of the study was to evaluate the impact of information level on quality of life in cancer patients previously studied for their information level.

Patients and methods

The information level was determined by means of a questionnaire that explored the degree of information on diagnosis and status of disease, the patient's interpretation of his/her disease status, and his/her satisfaction with the information received. Quality of life was evaluated, some months after evaluation of the information level, by means of the Functional Living Index for Cancer (FLIC) and the State-Trait Anxiety Inventory (STAI 1-2).

Results

A total of 175 patients were studied. Information was adequate in 53.7% of patients. An adequate level of information was present more frequently among patients aged ≤65 years and in those patients followed at a cancer institute. There was no difference in the quality of life of adequately versus inadequately informed patients. Satisfaction with the information received influenced quality of life in both age groups. Objective clinical variables (active disease present and ongoing treatment) negatively affected quality of life in patients <65 years, whereas the subjective perception of the presence of disease was associated with a worse quality of life in older patients.

Conclusions

In the study, although the level of information did not affect the quality of life, satisfaction with the information was associated with a better quality of life. The finding stresses the importance of a sensible disclosure of diagnosis and prognosis.
A First Survey of Organized Cervical Cancer Screening Programs in Italy
Authors: Ronco Guglielmo , Iossa Anna , Naldoni Carlo , Pilutti Silvia , Anghinoni Emanuela , Zappa Marco , Palma Paolo Dalla , Ciatto Stefano , Segnan Nereo ,   The GISCi working group on organization and evaluation, Schincaglia A. Patrizia , Davi Dino , Garutti A. Paola , Prandi A. Sonia , Canuti A. Debora , Falcini Fabio , Borsari A. Silvana , Cristiani Paolo , Fattorini Gianni , Collina A. Natalina , Dataro Pier Giorgio , Bondi Arrigo , Ronco Guglielmo , Vineis Clemente , Giudici Mauro , Penna Angelo , Anghinoni A. Manuela , Peasso Riccardo , Pinarello A. Antonella , Colle Giuseppe , Palma Paolo Dalla , Vannuccini Luca , Martini A. Alda , Ninci Giorgio , Giraldi Mauro , Giraldi Mauro , Berti Franco , Ballantini Maurizio , Mirri Francesco , Iossa A. Anna , Branca A. Margherita , di Giacomo Carlo , Principe Cesare , Brezzi A. Silvia , Sabbadini A. Franca , Zatelli A. Marella
Published: April 2018

In Italy, where no national screening program for cervical cancer exists, organized programs have developed on a local basis. We performed the first survey of existing organized programs by mailing a standard questionnaire to a large network of possibly involved services. For the present survey, a program was defined as organized if personal invitations were sent. We identified 29 already active organized programs and 4 others in a starting phase. The target population of active programs included 2,074,820 women in the age range 25-64 years, corresponding to 13.5% of the Italian female population of the same age. The situation is rapidly evolving since many regional programs are being implemented. Most programs followed Italian and European recommendations as regards the age limits, interval between screening rounds, presence of a fail-safe system for women referred for colposcopy, presence of protocols for diagnostic workup and treatment, and presence of referral centers for such phases. However, many programs did not meet national guidelines as regards the size of laboratories interpreting smears, which were frequently small. Second-level referral centers also frequently had a very small activity. The average (weighted for size of the invited population) compliance to invitation and coverage (proportion of women with at least one test in the last 3 years) was 32.6% and 66.0%, respectively, therefore needing to be improved. Compliance to colposcopy (weighted for number of referred women) was 81.4%. We found a very high variability in the proportion of women referred for colposcopy that could only be partly explained by different referral protocols and could depend on different criteria of smear interpretation: the average (weighted for number of tested women) was 2.01%. A need for improvement in the process of evaluation and for homogenization of criteria of cytology interpretation was identified: work in this regard is ongoing.
Postmastectomy Radiotherapy and Concomitant Adjuvant Chemotherapy Versus Adjuvant Chemotherapy Alone in Premenopausal Breast Cancer Patients with Positive Axillary Nodes
Authors: Micheletti Enrico , La Face Beniamino , Huscher Alessandra , Catalano Gianpiero , Ambrosi Enrica , Marini Giovanni , Simoncini Edda
Published: April 2018

Aims

To evaluate the efficacy of postmastectomy radiotherapy (RT) combined with adjuvant chemotherapy compared to adjuvant chemotherapy alone as regards overall survival (OS), overall disease-free survival (ODFS), local disease-free survival (LDFS) and distant disease-free survival (DDFS).

Methods

We reviewed retrospectively two non-randomized groups of premenopausal high-risk breast cancer patients treated from 1985 to 1990 in the following Institutions: Department of Radiation Oncology of Brescia University, “Istituto del Radio O. Alberti” (IRA), and Department of Oncology of Brescia Hospital “Beretta Foundation” (BF). A total of 163 patients was found to satisfy the criteria of the current analysis: 81 patients received adjuvant chemotherapy alone [6 cycles CMF(1-8)] at BF and 82 patients received postoperative radiotherapy and chemotherapy [8 cycles CMF(1-21)] at IRA. A modified CMF schedule was chosen at IRA to avoid the feared increase in toxicity due to the association with RT. Primary surgical treatment was modified radical mastectomy with axillary node dissection in both cases.

Results

A statistically significant improvement in OS was found in systemic adjuvant therapy patients compared to those also given RT (77.6% vs 59%; P = 0.0025). No statistically significant improvement in ODFS was found in the CMF(1-8) arm compared to the RT and CMF(1-21) stm: 51.6% vs 43.6%; P = 0.46. A statistically significant improvement in LDFS at 5 years was found in irradiated patients (89.3% vs 76.2%; P <0.05). The DDFS was also improved, although without evidence of statistical significance, in the CMF(1-8) group: at 5 years 65% vs 44% ( P = 0.059).

Conclusions

The study confirmed that RT reduces the risk of local recurrence but without a statistically significant reduction in mortality. The lack of a survival benefit may somehow reflect the dose reduction in CMF(1-21). The evidence that CMF(1-8) offers undoubtable advantages over the CMF(1-21) regimen in OS and, perhaps, in distant control suggests that the dose intensity of CMF in this setting may also be important. In fact, although many CMF(1-8) patients received a dose intensity lower than 100%, 95% of them received a dose intensity higher than the maximum one of the CMF(1-21) patients. Although our results should be interpreted with caution, they seem to provide further rationale for testing the association of postoperative radiotherapy and the CMF(1-8) regimen in stage II breast cancer with positive nodes and treated with demolitive surgery, as already done in the conservative management of breast cancer, also in view of the new support therapies now available (i.e. hematologic growth factors).
Increasing Doses of 5-Fluorouracil and High-Dose Folinic ACID in the Treatment of Metastatic Colorectal Cancer
Authors: Meregalli Maurizio , Martignoni Giancarlo , Frontini Luciano , Zonato Sabrina , Pavia Gianfranco , Beretta Giovanni
Published: April 2018

Aims and background

Combined 5-fluorouracil (5FU) and folinic acid (FA) is the first-line treatment of metastatic colorectal cancer. The aims of this study were to individualize the dose of 5FU in a weekly schedule in which the maximum tolerated dose of 5FU is administered to each patient, and to evaluate the impact of increasing 5FU doses on response and survival.

Methods

Thirty-two patients (30 evaluable for response) with metastatic colorectal cancer were treated with weekly intravenous doses of FA 150 mg/m2 and a fast infusion of 5FU, at an initial dose of 600 mg/m2 which was increased by 60 mg/m2 every week until the appearance of a side effect, in order to determine the maximum tolerated dose for the patient.

Results

We obtained 11 objective responses (36.7%, median survival 22 months) and 15 disease stabilizations (50%, median survival 15 months); there were four cases of progressive disease (13.3%, median survival 4 months). The overall survival was 15 months. Twenty-eight patients (87.5%) tolerated 5FU doses of 720 mg/m2 or more.

Conclusions

Weekly 5FU with high-dose FA modulation can be individualized by dose escalation. A 5FU dose of 720 mg/m2 per week seems to be critical, as higher doses are no more effective and lead to severe side effects. This schedule gives good results in terms of response, even though the complete response rate remains low.
Suramin in Combination with 5-Fluorouracil (5-FU) and Leucovorin (LV) in Metastatic Colorectal Cancer Patients Resistant to 5-FU+LV-Based Chemotherapy
Authors: Falcone Alfredo , Pfanner Elisabetta , Brunetti Isa , Ailegrini Giacomo , Lencioni Monica , Galli Costanza , Masi Gianluca , Danesi Romano , Antonuzzo Andrea , Del Tacca Mario , Conte Pier Franco
Published: April 2018

Aims and background

Suramin has been shown to be of interest as a potential new anticancer agent because of its capacity to inhibit the binding of several growth factors to their receptors and to inhibit the growth of cancer cells in vitro. Since multi-autocrine loops involving growth factors which are antagonized by suramin have been demonstrated in colorectal cancer, we previously evaluated the activity of suramin in patients with advanced colorectal cancer. Interestingly, in this study three patients who had received 5-FU+LV after suramin, although heavily pretreated with fluoropyrimidines, obtained an objective response. This observation was intriguing as it might have been that suramin had changed the biology of the tumor, making it sensitive to 5-FU+LV. We therefore conducted the present study to investigate the possibility that suramin might overcome the resistance to 5-FU+LV.

Methods and study design

Only colorectal cancer patients with metastatic and progressive disease during 5-FU+LV-based chemotherapy were eligible for this study. Suramin was administered for eight weeks at doses determined by means of a computer-assisted dosing algorithm that used Bayesian pharmacokinetics to maintain suramin plasma concentrations of 200-250 μg/ml. 5-FU was administered weekly at a dosis of 450 mg/m2 halfway through a two-hour infusion of I-LV 250 mg/m2 starting one week after the initiation of suramin for a maximum of 26 weeks.

Results

Treatment was relatively well tolerated, but no objective responses were observed after the accrual of 13 patients in the first stage of the trial. Consequently, the trial was interrupted according to the initial two-stage sampling design.

Conclusions

The present study does not support the hypothesis that suramin might overcome resistance to 5-FU+LV and its use in colorectal cancer is not recommended.
Phase II Study of the Activity and Tolerability of a Combined Regimen of High-Dose Epirubicin and Cisplatin in Stage IIIb and IV Non-Small Cell Lung Cancer
Authors: Clerici Maurizia , De Marinis Filippo , Piazza Elena , Frontini Luciano , Tucci Enrico , Barni Sandro , Bretti Sergio , Luporini Gino , Intini Claudio
Published: April 2018

Aim

To explore the feasibility and activity of a combined regimen of high-dose epirubicin and cisplatin as an alternative to current treatments for non-small cell lung cancer (NSCLC).

Method

Forty-four patients with stage IIIb or IV NSCLC, median Karnofsky index 90, were enrolled. Epirubicin (60 mg/m2) was administered on days 1 and 2 and cisplatin (100 mg/m2) on day 1. Treatment was repeated every 21 days for a maximum of six cycles. A hematopoietic growth factor (G-CSF) was used only for patients reaching codified nadir count values.

Results

A total of 130 cycles were administered with a mean of 2.9 cycles per patient. Of 41 assessable patients one showed a complete response and 15 had partial responses (overall response rate, 39%). Grade 3 or 4 leukopenia and grade 3 hemoglobin toxicity were seen in 40% and 14%, respectively, of the administered cycles. The most common nonhematologic toxic events were nausea and vomiting, mucositis, anorexia, and asthenia.

Conclusions

This epirubicin-cisplatin regimen seemed effective and was generally well tolerated, and therefore suitable for use in an outpatient setting.
Nutritional Support in Patients with Cancer of the Esophagus: Impact on Nutritional Status, Patient Compliance to Therapy, and Survival
Authors: Bozzetti Federico , Cozzaglio Luca , Gavazzi Cecilia , Bidoli Paolo , Bonfanti Giuliano , Montalto Fabrizio , Parra Hector Soto , Valente Maurizio , Zucali Roberto
Published: April 2018

Aims and background

The multimodal approach to patients with esophageal squamous cell carcinoma often includes poly-chemotherapy combined with radiation therapy. Cancer dysphagia and drug-related anorexia, mucositis and vomiting can all lead to malnutrition. The aim of this study was to analyze the impact of the administration of enteral nutrition (EN) on the patient's nutritional status, tolerance of chemotherapy and radiotherapy, and final oncological outcome.

Methods

Fifty esophageal cancer patients who were to be submitted to chemotherapy (days 1-4 5-fluorouracil (FU) 1 g/m2/day and cisplatin (CDDP) 100 mg/m2/day 1) for two cycles plus radiotherapy (31 Gy) were referred to the Nutrition Support Unit prior to any therapy due to their malnourished status. Twenty-nine dysphagic patients received nutrition via tube (37 kcal/kg/day + 2.0 g proteins/kg/day for 34 days), while 21 others who were not dysphagic were given a standard oral diet (SD). The patients who received EN had a more severe weight loss than the SD patients (16.8% vs 12.8%, P <0.02).

Results

The dose of administered EN represented 86% of the planned support, and 70% of the nutritional therapy was administered in the home setting. Administration of EN support resulted in stable body weight and unchanged levels of visceral proteins, while SD patients had a decrease in body weight, total proteins and serum albumin ( P <0.01). There was no difference between the two groups in terms of tolerance and response to cancer therapy, suitability for radical resection and median survival (9.5 months).

Conclusions

EN in patients with cancer of the esophagus undergoing chemotherapy and radiotherapy is well tolerated, feasible even in the home setting, prevents further nutritional deterioration and achieves the same oncological results in dysphagic patients as those achieved in non-dysphagic patients.
Changes in Serum Lipid and Lipoprotein Levels in Postmenopausal Patients with Node-Positive Breast Cancer Treated with Tamoxifen
Authors: Vrbanec Damir , Reiner Željko , Belev Borislav , Pleština Stjepko
Published: April 2018

Tamoxifen has been used for a long time as an adjuvant hormonal treatment in breast cancer patients. We studied 62 newly diagnosed postmenopausal women, aged 50-79 years, with node-positive breast cancer and receiving adjuvant tamoxifen (20 mg per day). Total serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, apo AI, apo AII, apo B and Lp(a) were determined before the surgery and 3, 6, 9, 12 and 24 months after starting tamoxifen treatment. Tamoxifen significantly reduced total serum cholesterol (6.13 ± 1.20 mmol/L vs 5.21 ± 1.05 mmol/L) ( P <0.01), LDL-cholesterol (3.72 ± 0.70 mmol/L vs 2.93 ± 0.51) ( P <0.01) and Lp(a) (0.11 ± 0.07 g/L vs 0.02 ± 0.01 g/L) ( P <0.01). There were no changes in triglycerides or HDL-cholesterol serum levels during tamoxifen treatment. The results indicate that an additional beneficial effect of adjuvant tamoxifen therapy may be that it decreases cardiovascular risk in such patients.