bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening E-Cadherin Germline Mutations in Italian Patients with Familial Diffuse Gastric Cancer: An Analysis in the District of Urbino, Region Marche, Central Italy
Authors: Graziano Francesco , Ruzzo Anna Maria , Bearzi Italo , Testa Enrica , Lai Vittorio , Magnani Mauro 
Published: April 2018

Aims & Background Hereditary diffuse gastric cancer is a recently defined cancer syndrome caused by inactivating, heterozygous germline mutations in the E-cadherin gene (CDH1). To date, 16 truncating germline CDH1 mutations have been described in hereditary diffuse gastric cancer families in different ethnic groups, but so far, no investigation has been addressed to Italian patients. In the District of Urbino, Region Marche, Central Italy, gastric cancer is the most common tumor in men and it is the second in women after breast cancer. In this area, we investigated CDH1 mutations in patients who fulfilled the hereditary diffuse gastric cancer criteria. Material and Methods Consecutive patients with diffuse gastric cancer were considered eligible for the study. After pedigree analysis, patients who met the International Gastric Cancer Linkage Consortium criteria were studied for CDH1 mutations. After blood samples collection and DNA extraction, standard polymerase chain reaction and sequencing techniques were used for CDH1 analysis. Results In a study population of 98 patients with diffuse gastric cancer, 11 patients (11%) showed familial clustering and 3 of them met the International Gastric Cancer Linkage Consortium criteria for hereditary diffuse gastric cancer. None of the 3 patients showed inactivating germline mutation in CDH1. Conclusions According to recent studies, the frequency of CDH1 inactivating germline mutations in patients who fulfil the hereditary diffuse gastric cancer criteria may be lower than that reported in early investigations. The results of the present study in a population of Italian patients seem to confirm these data. It is likely that unidentified mutations in CDH1 or other involved genes contribute to diffuse gastric cancer susceptibility.
Coincidence of Thyroid Tumor and Thyroglossal Duct Remnants. Review of the Literature and Presentation of Three Cases
Authors: Astl Jaromír , Dušková Jaroslava , Kraus Jaroslav , Vlček Petr , Kodet Roman , Laštůvka Petr , Betka Jan 
Published: April 2018

Aims and Background The coincidence of benign or malignant thyroid tumors with thyroglossal duct remnant (TDR) cysts is rare. Although the precise etiology is still unclear, thyroid origin and spread from a primary site have been suggested and this obviously has important implications for the therapeutic approach. Three cases of thyroglossal duct carcinoma are presented and its management is discussed on the basis of the current rationale for treatment of thyroid cancer. The indication for surgery depends on positive findings in the thyroid gland (nodules, FNAB). The aim of this study was to review our experience in the management of papillary thyroid diseases associated with TDR. Materials and Methods The records of three patients with thyroid tumors associated with TDR treated at the Department of ENT and Head and Neck Surgery of the First Medical Faculty UK of Prague between January 1991 and January 2001 were analyzed. We searched for risk factors of thyroid carcinoma: history of ionizing radiation, history of thyroid diseases, age, tumor size, tumor spread and histopathological factors. Results We used a triple approach consisting of clinical and ultrasound examination and fine-needle aspiration biopsy for preoperative assessment. Our diagnostic and therapeutic procedures included TDR excision (Sistrunk or Schlange procedure) and total thyroidectomy. Although the therapeutic approach could be a matter of discussion, most patients agreed with our suggestion of relatively radical but non-mutilating treatment. Postoperative radiation or radioiodine ablation is considered in cases of TDR carcinoma or thyroid carcinoma associated with TDR. Oncological follow-up included clinical and ultrasound examination three times during the first year, twice in the second year, and once yearly thereafter. Tumor marker evaluation and/or scintigraphy were performed 6, 12 and/or 24 months following surgery.
Intraoperative Radiotherapy during Breast Conserving Surgery in Patients Previously Treated with Radiotherapy for Hodgkin's Disease
Authors: Intra Mattia , Leonardi Maria Cristina , Gatti Giovanna , Vento Anna Rita , Ciocca Mario , Veronesi Paolo , Bassani Guillermo , Santos Gabriela Rosali Dos , Rodriguez Julia , Luini Alberto , Orecchia Roberto , Veronesi Umberto 
Published: April 2018

Aims and background Women who have received radiotherapy for Hodgkin's disease have an increased risk of developing breast cancer. Breast-conserving surgery followed by breast irradiation is generally considered to be contraindicated in such patients owing to the high cumulative radiation dose to the breast. Mastectomy is therefore recommended as the preferred treatment option in these women. Methods We report 3 patients affected by breast cancer who had previously been treated with mantle radiation for Hodgkin's disease and on whom breast-conserving surgery and full-dose intraoperative radiotherapy with electrons (ELIOT) were performed. Results A total dose of 17 Gy (prescribed at 100% isodose) in one case and 21 Gy (at the 90% isodose) in two cases was delivered directly to the mammary gland without acute complications and with good cosmetic results. Conclusions In women previously irradiated for Hodgkin's disease, ELIOT could avoid repeat irradiation of the whole breast, thereby permitting conservative surgical treatment.
Efficacy and Safety of Trastuzumab as a Single Agent in Heavily Pretreated Patients with Her-2/NEU-Overexpressing Metastatic Breast Cancer
Authors: Sawaki Masataka , Ito Yoshinori , Tada Keiichiro , Mizunuma Nobuyuki , Takahashi Shunji , Horikoshi Noboru , Kasumi Fujio , Akiyama Futoshi , Sakamoto Goi , Imai Tsuneo , Nakao Akimasa , Hatake Kiyohiko 
Published: April 2018

Aims and background The human epidermal growth factor receptor 2 (HER2) protein is a unique and useful target for antibody therapy against breast cancers that overexpress the HER-2/neu gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab, was approved for clinical use in the United States in 1998. It became available in Japan in June 2001. This study focuses on the efficacy and safety of trastuzumab as a single agent in second-third line treatment of HER2/neu-overexpressing metastatic breast cancer. Study design Between June 2001 and May 2002, we treated 62 patients with trastuzumab, as a single agent or in combination chemotherapy, for second-third line treatment of HER2-overexpressing metastatic breast cancer. Twenty-seven of 62 patients were treated with trastuzumab as a single agent. We reviewed retrospectively the efficacy and safety of the drug given as a single agent. The expression of HER2 was determined by immunohistochemical staining. All patients received a standard loading dose of 4 mg/kg followed by 2 mg/kg weekly. Results Patients received a median of 16.7 weekly infusions (range, 1–66 infusions). Trastuzumab therapy was generally well tolerated. Clinically severe adverse events (grade 3 or 4) included hypotension (7.4%), and hypoxia (3.7%). Grade 1 to 2 toxicity included fever (11.1%) and diarrhea (3.7%). Infusion-related reactions were infrequent, as were serious hematologic complications. Cardiotoxicity did not occur in the study. Three patients had a complete and 3 a partial response, 3 had no change, 17 had progressive disease, and one was not evaluated. The overall response rate in the 26 patients with available data was 23.1% (95% confidence interval, 5.7–40.4). The median duration of response was 6.4 months (range, 2.5–14.0). The median time to progression was 3.1 months (range, 0.2–16.7). Response rates differed by metastatic site as follows: lung 0% (0/12), bone 10.0% (1/10), liver 0% (0/8), skin 50.0% (4/8), lymph nodes 42.9% (3/7), brain 0% (0/2). Conclusions Molecular target therapy with trastuzumab appears safe and is generally well tolerated. For treatment of metastatic breast cancer, single agent therapy produces a durable response in some patients but lacks sufficient efficacy. Single agent use of trastuzumab is a viable option for treatment in cases with non-life-threatening disease without visceral metastasis.
Weekly Docetaxel as Second-Line Therapy in Non-Small Cell Lung Cancer: A Phase II Study
Authors: Rossi David , Graziano Francesco , Ugolini Marcello , Dennetta Donatella , Alessandroni Paolo , Catalano Vincenzo , Giordani Paolo , Fedeli Stefano Luzi , Fedeli Anna , Catalano Giuseppina 
Published: April 2018

Introduction Single-agent docetaxel is active as second-line chemotherapy in non-small cell lung cancer (NSCLC) pretreated patients; seven phase II studies have shown response rates of about 20% and 9 months of median survival. Two phase III studies documented a survival benefit at 1 year compared to BSC and vinorelbine or ifosfamide. Recent trials indicate acceptable activity and a good safety profile of weekly docetaxel with doses of 25–43 mg/m2. The aim of our study was to confirm this evidence and to evaluate activity and toxicity of weekly docetaxel at the dose of 40 mg/m2. Patients and methods Twenty-one patients with NSCLC entered the study (7 stage NIB and 14 stage IV): 13 males and 8 females. Median age was 66 years (range, 53–75). ECOG was O in 6, 1 in 9 and 2 in 6 patients. All patients were pretreated with a first-line chemotherapy (13 patients progressed soon after the first line); 6 of them received palliative radiotherapy on the chest. The treatment consisted of weekly docetaxel, 40 mg/m2 in 1 hr for six weeks with two weeks of rest (1 cycle). A total of 87 administrations was delivered (median, 4; range, 1–12). Responses All patients were assessable for response (according to the “intent-to-treat principle”) and for toxicity. No complete or partial remission was observed; 2 minor responses (9.5%), 1 stable disease (5%), 8 progressive diseases (38%) were documented. Seven patients dropped out the study due to severe toxicity (33.5%) and 3 due to early death (14%). Median survival was 3 months (range, 1–17), and 1-year survival was 9.5%. Toxicity was as follows: grade 4 diarrhea in 1; grade 3 asthenia in 8 (38%), grade 3 stomatitis in 2; grade 3 neutropenia in 1; allergic reactions in 2. No treatment-related death was recorded. Conclusions The trial showed only very modest activity of weekly docetaxel, with severe side effects that induced us to stop the accrual in order to prevent other worse toxicities. We therefore concluded that a dose of 40 mg/m2 of weekly docetaxel is not manageable and does not seem to provide a real benefit in terms of response and quality of life.
Regionally Advanced Nasopharyngeal Carcinoma: Long-Term Outcome after Sequential Chemotherapy and Radiotherapy
Authors: Palazzi Mauro , Guzzo Marco , Bossi Paolo , Tomatis Stefano , Cerrotta Annamaria , Cantú Giulio , Locati Laura D , Licitra Lisa 
Published: April 2018

Aims and background To evaluate the long-term clinical outcome of 61 patients with regionally advanced nasopharyngeal carcinoma treated with sequential chemotherapy and radiotherapy within a phase II trial. Methods The trial evaluated a combined modality regimen including 3 cycles of induction polychemotherapy (epirubicin 70 mg/m2 d1, and cisplatin 100 mg/m2 d1, both recycled every 3 weeks) followed by definitive radiotherapy to the primary site (64–70 Gy) and the neck (50–70 Gy). Patients included in the trial had pathologically confirmed nasopharyngeal carcinoma; stage (UICC 1987) T-any, N2-3, M0; ECOG performance status 0–1. Sixty-one patients were enrolled between 1990 and 1996; stage according to UICC 1997 was IIb in 8%, III in 36% and IV in 56% of the patients; histology was WHO type 1–2 in 11% and WHO type 3 in 89% of cases. Minimum follow-up of 33 surviving patients is 5.2 years. Results Clinical failure has been observed in 30 patients (49%): initial failure, observed within the third year of follow-up in all but one case, was local alone in 6 (20%), regional alone in 10 (33%), local and regional in 1 (3%), regional and distant in 1 (3%), and distant alone in 12 patients (40%). Seven patients received salvage surgery to the neck, 2 of them still disease-free at 10 and 11 years from salvage surgery; 4 patients with an isolated local relapse were re-irradiated, and one of them was alive and well at 6.5 years from salvage radiation. At 5-year local control, regional control and distant metastasis-free rates were 83%, 74% and 73%, respectively; overall and disease-free survival were 64% and 51%. Late effects of initial treatment, as evaluated in 30 patients surviving 5 years without relapse, were generally acceptable, but some degree of xerostomia, dental damage, trismus and hearing loss were reported by a significant proportion of patients (respectively 100%, 88%, 76% and 86%). Conclusions In our experience, long-term clinical cure of regionally advanced nasopharyngeal carcinoma was obtained in 51% of cases treated with chemotherapy and radiotherapy. Salvage treatments (neck surgery, local re-irradiation) are worthy, as they increase the cure rate by approximately 10%, raising 5-year survival to over 60%. Late effects are significant, calling for refinements in radiation technique, better integration with chemotherapy to possibly decrease the need for higher radiation dose, and/or use of effective radioprotectants.
Radiotherapy of Liver Malignancies. From Whole Liver Irradiation to Stereotactic Hypofractionated Radiotherapy
Authors: Greco Carlo , Catalano Gianpiero , Di Grazia Alfio , Orecchia Roberto 
Published: April 2018

Aims and background Until recently radiotherapy of hepatic malignancies has played a limited role due to the well-known limited radiotolerance of the liver. The aim of this paper is to review the available data on the risk of radiation-induced liver disease (RILD) and to define the modern role of radiotherapy in the management of patients with metastatic or primary liver malignancies. Methods The advent of three-dimensional conformal treatment planning with dose-volume histogram analysis has made the study of partial liver irradiation possible. Limited portions of the liver may withstand high doses of radiation with minimal risk of RILD. Patients with solitary unresectable liver tumors may be treated with high-dose radiotherapy with curative intent. Recently, the feasibility of stereotactically guided treatment techniques with a single fraction or few treatment sessions has been explored in numerous institutions. Results The radiation tolerance of the whole liver found by several investigations is in the order of approximately 30 Gy, which seriously restricts its clinical application. The role of whole liver irradiation therefore appears of limited benefit in the palliation of patients with multiple liver metastases. The use of three-dimensional conformal techniques has made partial liver irradiation possible to doses in the 70–80 Gy range with conventional fractionation. At least two published series have reported improved local control and survival rates with dose escalation with three-dimensional conformal radiotherapy in patients with unresectable liver metastases. Similar outcomes have been recently reported with single dose (or hypofractionated) stereotactic radiotherapy both in metastatic and primary hepatic malignancies with minimal morbidity. Accurate target delineation and treatment reproducibility are the key to the success of this novel treatment approach, and specific treatment planning techniques and patient setup procedures must be developed to implement it. Conclusions Stereotactic high-dose radiotherapy is technically feasible for the treatment of inoperable liver malignancies, with the potential of high local control and low morbidity. Definitive evidence on the clinical advantages of this technique over other more established treatments can only be gathered from well-designed clinical studies.
Outcome of Laparoscopic Splenectomy for Malignant Hematologic Diseases
Authors: Cavaliere Davide , Torelli Paolo , Panaro Fabrizio , Casaccia Marco , Ghinolfi Davide , Santori Gregorio , Rossi Edoardo , Bacigalupo Andrea , Valente Umberto 
Published: April 2018

Aim The role of laparoscopic splenectomy in the treatment of hematological diseases is still controversial. The aim of this study was to assess whether the benign or malignant nature of hematological diseases may influence the outcome of laparoscopic splenectomy. Patients and methods Between August 1997 and March 2002, 63 unselected patients with hematologic diseases underwent a laparoscopic splenectomy. Patients were divided into two groups according to the benign (Group A, 38 patients) or malignant (Group B, 25 patients) nature of the hematological diseases. Results Patients in group B were significantly (a) older, (b) had larger spleens that more frequently needed accessory incisions for specimen retrieval, (c) had greater transfusion requirements, and (d) were fed later than patients in group A. There were no statistically significant differences among the two groups in terms of (a) body-mass index, (b) operative time, (c) conversion rate, (d) blood loss, (e) pain medication requirements, and (f) hospital stay. Two postoperative deaths occurred among patients in group B, but none of them was related to surgery. Conclusions The results of the study showed that: a) the nature of the disease does not influence the outcome of laparoscopic splenectomy, b) the size of the spleen might increase the risk of conversion, but it is no longer a contraindication to laparoscopic splenectomy, and c) laparoscopic splenectomy can be effectively performed in the treatment of malignant hematologic diseases.
Early Detection of Recurrences in the Follow-up of Primary Breast Cancer in an Asymptomatic or Symptomatic Phase
Authors: Perrone Maria Antonietta , Musolino Antonino , Michiara Maria , Di Biasio Beatrice , Bella Mariangela , Franciosi Vittorio , Cocconi Giorgio , Camisa Roberta , Todeschini Renata , Cascinu Stefano 
Published: April 2018

Aims and background Periodic follow-up after primary treatment for breast cancer is a common procedure for the early detection of recurrent disease in the asymptomatic state. Anyway, there is no clinical evidence that treatment of metastases may improve the prognosis if applied in the asymptomatic state. The aim of the present study was to investigate the modality of detection of the first relapse in the asymptomatic vs the symptomatic state. Methods We retrospectively analyzed 717 breast cancer patients who had been consecutively referred to the Parma Oncology Division during the period 1986 to December 1988. Recurrences were detected in the course of periodic follow-up. Results A total of 211 of the 408 patients evaluated had a first relapse with a median follow-up of 94.7 months. Local and distant recurrences were 49% and 47%, respectively. Bone recurrences represented 24% of the total first recurrences, then chest wall recurrences in 23%, local regional nodes in 13%, lung in 7%, liver in 4%, and brain in 2%. The distribution of the studied patients according to recurrence site and asymptomatic or symptomatic state was different: 69% of asymptomatic patiens (110) had a local recurrence vs 31% of symptomatic patients (101). A difference in survival was recorded in favor of cases detected in the asymptomatic state (P <0.001). Conclusions The present study suggests that an early detection of local recurrence might have a favorable impact on the prognosis of patients followed after primary treatment for breast cancer. It should be considered that any difference in survival could also be explained by several “biases” and that breast cancer follow-up is still an area of investigation open to discussion in which many questions remain to be clarified.
Design and Development of New Combinations of the CMF Agents with Taxanes (Paclitaxel or Docetaxel) in Advanced Breast Cancer: A Feasibility Study
Authors: Cocconi Giorgio , Salvagni Stefania , Passalacqua Rodolfo , Ferrozzi Francesco , Camisa Roberta 
Published: April 2018

Aims and background We previously designed and tested combinations made up of the CMF agents, two at a time by rotation, and of doxorubicin or epirubicin. The present study was aimed to similarly test new combinations made up of the CMF agents, two at a time by rotation, and paclitaxel or docetaxel. Methods The doses of each taxane were escalated with the objective of reaching at least a single dose level of 90 mg/m2 of paclitaxel and 45 mg/m2 of docetaxel on days 1 and 8 of each four-week cycle. Thirty-two patients with advanced breast carcinoma were randomized to receive increasing doses of paclitaxel (45, 65, 80, 90 and 100 mg/m2) or docetaxel (30, 35, 40, 45 and 50 mg/m2) together with the CMF agents at the same dose as that used in the conventional regimen. Each dose level was administered to a triplet of patients. No direct comparison of the two taxanes was made. Results The fourth dose level was reached for paclitaxel and docetaxel. The most important toxicities were grade 4 neutropenia and grade 1-2 nausea/vomiting and stomatitis. The objective response rate, assessed only after the third cycle at any dose level, was 31% (95% CI, 15-47%). Conclusions The combinations of the CMF agents (two at a time in rotation) with paclitaxel (90 mg/m2) or docetaxel (45 mg/m2) on days 1 and 8 of each four-week cycle are feasible and lead to definite signs of therapeutic activity, and the side effects are generally mild. Further studies are therefore warranted.
Long-Term, weekly One-Hour Infusion of Paclitaxel in Patients with Metastatic Breast Cancer: A Phase II Monoinstitutional Study
Authors: Lombardi Davide , Crivellari Diana , Scuderi Cristina , Magri Maria Donatella , Spazzapan Simon , Sorio Roberto , Di Lauro Vincenzo , Scalone Simona , Veronesi Andrea 
Published: April 2018

Aims and background A dose-dense therapy with weekly paclitaxel given as a 1-hr infusion yielded a 53% overall response rate in breast cancer patients resistant to anthracyclines, with a remarkable lack of neutropenia (Seidman, 1998). We performed a monoinstitutional phase II trial in order to confirm these interesting results. Patients and methods Eligibility criteria included advanced breast cancer and no taxane pretreatment. Paclitaxel was administered weekly at the dose of 90 mg/m2 (60 mg/m2 in patients at high risk of toxicity) by 1-hr iv infusion. Fifty-eight patients entered the trial. Median age was 54 years (range, 38-72). Performance status was good (median 1; range, 0-2). Fifty-two patients were pretreated with anthracyclines. Results A total of 1,004 weekly paclitaxel infusions were administered (median, 19 per patient; range, 4-43). The median delivered dose intensity was 67.4 mg/m2/week (range, 43-86). Twenty-eight of the 58 assessable patients obtained an objective response (48%), 15 had stable disease (26%) and 15 progressed (26%). The overall response rate was 48% (95% confidence interval, 35-61%) with 5 complete responses (8%). In anthracycline-pretreated patients, 23/52 (44%) responses were observed. Median duration of response was 5 months (range, 3-27). Toxicity was acceptable apart from a case of pulmonary embolism in a 70-year-old patient, 1 case of congestive heart failure in an anthracycline-pretreated patient aged 64, and 9 cases of G3 neutropenia. Peripheral neuropathy was observed in 38 patients (64%), usually of a mild grade; alopecia in 45 patients (78%) and onychopathy in 16 (28%), usually of a mild grade apart from 2 cases requiring treatment interruption. Tachycardia and atrial fibrillation occurred in a 55-year-old woman. Conclusions Our data seem to confirm the activity and safety of this approach even in a heavily pretreated population of patients. Its combination with other active drugs needs to be further investigated in clinical trials.