bluuebunny/crossref_metadata_2025 huggingface dataset:
Limited-Stage Small-Cell Lung Cancer Treated with Early Chemo-Radiotherapy: The Impact of Effective Chemotherapy
Authors: Scotti Vieri , Meattini Icro , Saieva Calogero , Rampini Andrea , De Luca Cardillo Carla , Bastiani Paolo , Mangoni Monica , Agresti Benedetta , Santomaggio Carmine , Di Cataldo Vanessa , Franzese Ciro , Livi Lorenzo , Magrini Stefano Maria , Biti Giampaolo
Published: February 2018

Aims and Background

Small cell lung cancer is characterized by an aggressive clinical course and a high sensitivity to both chemotherapy and radiotherapy. We present the Florence University experience in concurrent early radio-chemotherapy in patients affected by limited-stage small cell lung cancer, with particular emphasis on treatment safety, disease outcome and prognostic factors.

Methods and Study Design

Fifty-seven patients were treated between June 2000 and February 2005. All patients underwent platinum-based chemotherapy, administered intravenously following two different regimens, for at least three cycles. Eighteen patients (31.6%) received epirubicin and ifosfamide in 3-week cycles alternating with etoposide and cisplatin, administered on day 1 to 3; 39 patients (68.4%) received etoposide and cisplatin. A total of 6 cycles were planned. Radiotherapy was administered concurrently to the first cycle of etoposide and cisplatin.

Results

Clinical stage (P = 0.036) and number of chemotherapy courses (P = 0.009) emerged as the only significant death predictors at univariate analysis. Number of chemotherapy courses persisted as a significant death predictor also at multivariate regression analysis, with a reduced death risk for 5–6 chemotherapy cycles in comparison to 3–4 cycles (hazard ratio, 0.44). At a mean follow up of 38.5 months (standard deviation, 3.24 years; range, 6–164 months), considering the best overall tumor response achieved at any time during the whole treatment period, we obtained 32 complete responses (56.1%), 23 partial responses (40.3%) and 2 stable diseases.

Conclusions

Our analysis showed that concurrent early radio-chemotherapy in limited-stage small cell lung cancer treatment represents a safe and effective approach in patients. We confirmed the relevant impact on overall survival of effective chemotherapy delivery.
Pulmonary Resections: Cytostructural Effects of Different-Wavelength Lasers versus Electrocautery
Authors: Scanagatta Paolo , Pelosi Giuseppe , Leo Francesco , Furia Simone , Duranti Leonardo , Fabbri Alessandra , Manfrini Aldo , Villa Antonello , Vergani Barbara , Pastorino Ugo
Published: February 2018

Aims and Background

There are few papers on the cytostructural effects of surgical instruments used during pulmonary resections. The aim of the present study was to evaluate the parenchymal damage caused by different surgical instruments: a new generation electrosurgical scalpel and two different-wavelength lasers.

Methods

Six surgical procedures of pulmonary resection for nodules were performed using a new generation electrosurgical scalpel, a 1318 nm neodymium (Nd:YAG) laser or a 2010 nm thulium laser (two procedures for each instrument). Specimens were analyzed using optical microscopy and scansion electronic microscopy.

Results

Severe cytostructural damage was found to be present in an average of 1.25 mm in depth from the cutting surface in the patients treated using electrosurgical cautery. The depth of this zone dropped to less than 1 mm in patients treated by laser, being as small as 0.2 mm using the laser with a 2010 nm-wavelength and 0.6 mm with the 1318 nm-wavelength laser.

Discussion

These preliminary findings support the use of laser to perform conservative pulmonary resections (i.e., metastasectomies), since it is more likely to avoid damage to surrounding structures. Controlled randomized trials are needed to support the clinical usefulness and feasibility of new types of lasers for pulmonary resections.
Expression of the Hepatocyte Growth Factor and C-Met in Colon Cancer: Correlation with Clinicopathological Features and Overall Survival
Authors: Liu Yao , Li Qiaoyan , Zhu Liwei
Published: February 2018

Aim and Background

The hepatocyte growth factor (HGF)/c-Met signaling system has been implicated in the development and progression of colon cancer, but the relationship between the expression of HGF or c-MET and clinicopathologic features remains controversial. In the study, we analyzed the expression of HGF and c-Met in colon cancer and assessed the influence of the expression of this growth factor and its receptor on clinical and histological parameters and patient survival.

Methods and Study Design

We investigated the mRNA expression of HGF and c-Met with real-time PCR in 90 unselected colon carcinomas and the corresponding normal mucosa. Furthermore, HGF and c-Met protein expression was investigated with immunohistochemistry in all the samples.

Results

The mRNA and protein expression levels of HGF and c-Met were significantly higher in colon cancer than in matched normal mucosa. The protein level in most of the cases investigated was correlated with the mRNA level. Overexpression of HGF and c-Met, at both protein and mRNA levels, was correlated with depth of invasion, lymph node metastases and overall AJCC stage. According to univariate analysis, the mean survival time was shorter in the HGF-positive and c-Met-positive groups. Multivariate Cox analysis showed that high M stage and the expression of c-Met independently had a negative impact on overall survival.

Conclusions

The HGF/c-Met signaling pathway may be involved in the pathogenesis and progression of colon cancer. C-Met overexpression can be used as a useful parameter to evaluate the prognosis of colon cancer.
Expression of A1 and A3 Adenosine Receptors in Human Breast Tumors
Authors: Panjehpour Mojtaba , Hemati Simin , Forghani Mohammad Ali
Published: February 2018

Background

Adenosine receptors (A1, A2A, A2B, A3) play an important role in the regulation of growth, proliferation and death of cancer and normal cells. We recently showed the expression profile of A2A and A2B receptors in normal and tumor breast tissues. In the present study, we used semiquantitative RT-PCR to measure the A1 and A3 gene expression levels in normal and tumor breast tissues.

Methods

Breast tumors (n = 18) and non-neoplastic mammary tissues (n = 10) were collected and histologically confirmed to be neoplastic or non-neoplastic, respectively. Total RNA was extracted and reverse transcribed into cDNA, and PCR was performed under optimized condition for each receptor subtype. Amplification of beta-actin mRNA served as control for RT-PCR. The PCR products were separated on 1.7% agarose gels. The intensity of the bands was quantitated with ImageJ software after normalization against beta-actin expression.

Results

All breast tumor and normal tissue specimens expressed A1 and A3 adenosine receptor transcripts. However, we observed that the expression level of the A3 receptor in tumor tissues was 1.27-fold that of normal tissues, whereas there was no significant difference between the expression levels of A1 in normal and tumor tissues.

Conclusions

Interestingly, the results of the present study indicate that breast tumors exhibit a higher level of A3 transcripts (than normal tissues) and support the possible key role of A3 adenosine receptor in tumor development. However, further studies based on real-time quantitative RT-PCR are needed to identify the exact gene expression levels.
Unexpected Granular Cell Tumor in Abdominal Wall: Case Report and Literature Review
Authors: Panunzi Andrea , D'orazi Valerio , Toni Francesca , Coppola Giovanni Andrea , D'alessandro Valentina , Pontone Stefano , Pironi Daniele , Ortensi Andrea
Published: February 2018

Granular cell tumors (GCTs) are uncommon benign neoplasms deriving from Schwann cells of the peripheral nerve fibers. Although these tumors can be found anywhere in the body, the most frequent site is the tongue, followed by the chest wall and the arm. The abdominal wall is an extremely rare site for GCTs. These tumors are generally asymptomatic and have a slow growth rate. Today, thanks to their immunoreactivity to S-100 and CD68, the differential diagnosis is more straightforward than in the past. We report on a young patient affected by a GCT located in the upper third of the right rectus abdominis muscle. En bloc excision through a diamond-shaped skin incision allowed us to make a correct histological diagnosis, which was confirmed by the immunohistochemical findings. GCT, which is very rare in abdominal wall muscles, should be considered in the differential diagnosis, and surgical excision is the treatment of choice.
Prognostic Factors for Differentiated Thyroid Carcinoma and Review of the Literature
Authors: Zhao Yuan , Zhang Yang , Liu Xing-Jun , Shi Bing-Yin
Published: February 2018

Objective

Prognostic factors of differentiated thyroid carcinoma (DTC) are analyzed to justify the diagnostic and therapeutic modalities of DTC in current practice.

Methods

Patients undergoing curative resection for histologically diagnosed DTC (n = 150) were consecutively enrolled, and the clinical and pathological data were retrospectively reviewed.

Results

The DTC patient cohort consisted of 113 females (75.3%; mean age at the time of onset, 40.1 ± 12.0 yr) and 37 males (24.7%; 47.5 ± 16.2 yr). The pathological types of DTC included papillary thyroid carcinoma (n = 131, 87.3%) and follicular thyroid carcinoma (n = 19, 12.7%). The follow-up period ranged from 4.2 to 31 years, in which period 140 (93.3%) patients survived, 30 (20.0%) patients relapsed, and 10 (6.7%) patients died of DTC. Surgical procedures used for the curative resection consisted of near-total or subtotal thyroidectomy (n = 83, 55.3%), partial thyroidectomy (n = 64, 42.7%) and total thyroidectomy (n = 3, 2.0%). Out of those patients undergoing concomitant lymph node dissection (n = 63, 42.0%), 45 patients (71.4%) had detectable lymph node metastases. Postoperatively, 12 patients (8.0%) received external beam radiotherapy, 16 patients (10.7%) received chemotherapy, 37 patients (24.7%) received 131I therapy, and 66 patients (44.0%) received additional long-term L-T4 or thyroid hormone treatment. Age of onset, tumor size at initial visit, and rate of early metastasis showed statistically significant differences between the mortality group and the survival group (P <0.05) and between the recurrence group and the recurrence-free group (P <0.05).

Conclusions

Age, tumor size at initial visit, and early metastasis are prognostic factors for DTC, requiring a stratified management in clinical practice.
Pain Relief by Cyberknife Radiosurgery for Spinal Metastasis
Authors: Lee Sunyoung , Chun Mison
Published: February 2018

Aims and background

To report pain relief effect in patients with spinal metastases treated with Cyberknife® and to analyze the factors associated with pain relapse after initial pain relief.

Methods and study design.

We retrospectively analyzed patients with spinal metastasis treated with stereotactic body radiosurgery between April 2007 and June 2009. A total of 57 patients with 73 lesions were available for analysis with a median follow-up of 6.8 months (range, 1–30). Pain was assessed by a verbal/visual analogue scale at each visit: from 0 to 10. Pain relief was defined as a decrease of at least three levels of the pain score without an increase in analgesic use. Complete relief was defined as no analgesics or a score 0 or 1.

Results

Pain relief was achieved in 88% of the lesions, with complete relief in 51% within 7 days from the start of radiosurgery. The median duration of pain relief was 3.2 months (range, 1–30). Pain reappeared in 16 patients (27%). Spinal cord compression (P = 0.001) and performance status (P = 0.01) were predictive of pain relapse by multivariate Cox analysis. All 6 patients treated with solitary spinal metastasis experienced pain relief; 5 of them were alive without evidence of disease at a median of 16 months (range, 7–30).

Conclusions

As previous studies have shown, our study confirms that pain relief with spinal radiosurgery is around 90%. In particular, long-term pain relief and disease control was observed in patients with solitary spinal metastasis.
CK19, CK20, EGFR and HER2 Status of Circulating Tumor Cells in Patients with Breast Cancer
Authors: Tunca Berrin , Egeli Unal , Cecener Gulsah , Tezcan Gulcin , Gokgoz Sehsuvar , Tasdelen Ismet , Bayram Nuran , Tolunay Sahsine , Umut Gorkem , Demirdogen Elif , Erturk Elif , Ak Secil , Cetintas Sibel , Evrensel Turkkan
Published: February 2018

Aims and background

The major cause of death in breast cancer patients is metastasis. Various biomarkers have been used for the early detection of circulating tumor cells in the peripheral blood of breast cancer patients. The aims of the current study were to analyze circulating tumor cells in the blood of breast cancer patients by investigating EGFR, CK19, CK20 and HER2 expression profiles and to evaluate their prognostic importance.

Methods

CK19, CK20 and EGFR gene expression profiles were evaluated in the blood samples of 84 female patients with primary invasive ductal breast cancer and 20 healthy female volunteers using SYBR green-based real-time qPCR assays. HER2 expression analyses were conducted in 46 patients who had an HER2-positive primary tumor and in 30 healthy women to determine the cutoff level of positivity.

Results

The positive rates of CK20, EGFR, CK19 and HER2 mRNA expression in the peripheral blood were 28.57% (24/84), 20.23% (17/84), 5.95% (5/84) and 2.17% (1/46), respectively. The high positive ratio of CK20 mRNA expression in the peripheral blood of breast cancer was identified for the first time in the current study. Significant differences were identified in CK20 expression status and several clinical parameters related with aggressiveness of tumors using a binary logistic regression analysis. Higher CK20-positive levels were observed in patients who had lymph node metastasis and advanced-grade primary tumors, which were estrogen receptor-negative. We have demonstrated that CK20 may be a novel biomarker that is useful to identify circulating tumor cells and predict breast cancer progression.

Conclusions

The results suggest that the investigation of CK20 mRNA with other biomarkers in the peripheral blood of breast cancer patients may be useful to monitor the presence of disseminated tumor cells in the blood circulation and to predict the prognosis of breast cancer.
Management of Advanced Genitourinary Tumors
Authors: Biondani Pamela , Verzoni Elena , Procopio Giuseppe
Published: February 2018

The management of advanced genitourinary tumors is rapidly evolving thanks to the clinical availability of several targeted drugs with different mechanisms of action. Among clinicians, in-depth knowledge of all the aspects of the disease, together with the capacity to interpret and accurately correlate clinical data and imaging findings, are strongly needed. Moreover, the optimization of treatment sequences might lead to better disease control with respect to prognostic categories, radiological monitoring and newer biomarkers. Among the genitourinary tumors, only few data are available on bladder, testicular and penile cancers. Our report is supported by scientific and clinical experience in renal cell carcinoma and prostate cancer.
Effect of Maintenance Therapy with Dendritic Cells: Cytokine-Induced Killer Cells in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Shi Sheng Bin , Ma Ting Hang , Li Chun Hua , Tang Xiao Yong
Published: February 2018

Aims and background

The incidence and development of cancer are closely related to dysfunction of immune function. The immune system cannot identify and remove malignant and mutant cells, which cause tumor cells to escape from surveillance and clearance of the immune system. Immunobiological cancer therapy plays an important role in strengthening body immunological surveillance function and killing remaining tumor cells in the body. We investigated the role of DC/CIK (dendritic cell/cytokine-induced killer cells) immunobiological cancer therapy in maintenance therapy of advanced non-small cell lung cancer.

Methods

When 60 cases of non-small cell lung cancer patients in stage IIIb and IV reached stable disease after treatment with 4 cycles of a two-drug regimen with platinum, they were randomly divided into two groups. One group was treated with DC/CIK immunobiological cancer therapy, and the other was taken as a control group. Finally, cancer progression time and toxicity reaction of the two groups were evaluated.

Results

DC/CIK treatment prolongs progression-free survival (3.20 months [95% CI, 2.94–3.50] vs 2.56 months [95% CI, 2.39–2.73]; P <0.05). In the treatment group, the proportion of NK cells, T-cell subgroups CD3+, CD4+ and CD8+ had a significant change before and after treatment. Liver and kidney function and blood tests of the treatment group were within the normal range before and after treatment. In the treatment group, 1 case suffered from chest distress, 3 cases suffered from acratia, and 4 cases suffered from pyrexia.

Conclusions

DC/CIK treatment had potential benefit for patients with advanced non-small cell lung cancer compared with the control group and had no obvious side effects. DC/CIK treatment is a safe and effective method for maintenance therapy of advanced non-small cell lung cancer.
Treatment of Osteonecrosis of the Jaw (ONJ) by Medical Ozone Gas Insufflation. A Case Report
Authors: Ripamonti Carla Ida , Maniezzo Massimo , Pessi Maria Adelaide , Boldini Stefania
Published: February 2018

Osteonecrosis of the jaw (ONJ) is an adverse event reported in patients receiving cancer treatment, especially bisphosphonates and denosumab. A patient with multiple myeloma who underwent up to 22 intravenous zoledronic acid infusions without previous dental examination developed a devastating ONJ lesion in the right horizontal mandibular ramus. He was treated with local ozone gas applications every third day by means of a special bell to avoid O3 diffusion. Azithromycin 500 mg/day was administered for 10 days prior to the O3 applications. O3 therapy resulted in sequestration of the necrotic bone after a median of 15 applications, following which surgery was necessary to remove it. Interestingly, removal was possible without the resection of the healthy mandible edge because of the presence of the bone sequestrum. Medical O3 gas administration was effective and safe in a patient treated with bisphosphonates who developed a >2.5 cm ONJ lesion. Future research is needed to demonstrate the efficacy and tolerability of such treatment in a larger number of patients.
Neoadjuvant chemo-radiotherapy for locally advanced esophageal cancer: A monocentric study
Authors: Schena Marina , La Rovere Erika , Solerio Dino , Bustreo Sara , Barone Carla , Daniele Lorenzo , Buffoni Lucio , Bironzo Paolo , Sapino Anna , Gasparri Guido , Ciuffreda Libero , Ricardi Umberto
Published: February 2018

Aims and background

Multimodal therapy is a keystone of care in advanced esophageal cancer. Although neoadjuvant chemoradiotherapy is known to provide a survival advantage in selected cases, reliable prognostic and response predictive factors remain elusive. We report the outcome in a series of esophageal cancer patients treated at our center and the results of a retrospective analysis of epidermal growth factor receptor (EGFR) expression and EGFR/HER2 gene copy numbers taken as possible prognostic and predictive factors.

Methods and study design

Between 2001 and 2009, a total of 40 consecutive patients (34 men and 6 women; median age, 59 years) were treated for esophageal cancer. Treatment: cisplatin, 80 mg/m2 day 1, and 5-fluorouracil, 800 mg/m2/24 h on days 1–5, every 21 days, concomitant with 3D-conformal radiotherapy (54–59.4 in 30–33 fractions) for three up to four cycles. Surgery was performed in eligible patients 6–8 weeks after chemoradiation. EGFR expression and EGFR/HER2 amplification and gene copy number were studied by immunohistochemical analysis and fluorescence in situ hybridization, respectively.

Results

Acceptable toxicity following chemoradiation was recorded, with G3–G4 hematological toxicity in 20% of patients and G3–G4 dysphagia in less than 10%; 14 (35%) patients achieved complete response and 19 (48%) partial response; 18 underwent surgery after chemoradiation, of which 8 (20%) achieved pathologic complete response. The median survival was 29 months (95% CI, 25.7–32.1): 42 months for the resected and 20 for the unresected patients. EGFR and HER2 analysis in 28 patients showed that 89% had immunohistochemical EGFR expression, with 5 cases of EGFR and 10 of HER2 gene gain without a significant difference in response rate and survival in these patient subgroups.

Conclusions

Our results suggest a better outcome in patients who underwent surgery after chemoradiation. A larger sample size is necessary to clarify the role of EGFR and HER2 gene gain in predict response and survival.
Cell Damage of Hepatoma-22 Cells Exposed to Continuous Wave Ultrasound
Authors: Wang Pan , Wang Xiaobing , Liu Quanhong
Published: February 2018

Aims and background

The cellular response of hepatoma-22 cells to ultrasonic irradiation and the potential cause for the action were evaluated.

Methods and study design

Hepatoma-22 cells were subjected to ultrasound irradiation at a frequency of 2.17 MHz and a spatial average intensity of 1.6 W/cm2 for variable periods of time, and several biological parameters were analyzed. The terephthalic acid (TA) dosimetry method was used to evaluate the efficacies of irradiation parameters on the acoustic cavitation activity by monitoring hydroxyl radical (OH) production. Lactate dehydrogenase (LDH) leakage was assayed to investigate cell membrane integrity. The polarization value of fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was measured to monitor plasma membrane fluidity. The malonaldehyde content in cells was determined to reflect lipid peroxidation. Trypan blue exclusion was used to detect cell viability. Additionally, electron microscopy was used to observe morphological changes. The generation of intracellular reactive oxygen species, mitochondria swelling and the loss of mitochondria membrane potential were also investigated.

Results

The results showed that 1) the concentration of ·OH production by ultrasonic irradiation in air-saturated cell suspensions increased as ultrasound exposure time increased; 2) compared with control, lactate dehydrogenase leakage, the polarization value of 1,6-diphenyl-1,3,5-hexatriene, malonaldehyde content and cell lysis were significantly elevated when cells were treated by ultrasound for 60 s; 3) cytotoxicity by ultrasound irradiation was also accompanied by an increase in production of intracellular reactive oxygen species and dissipation of mitochondria membrane potential as well as by mitochondria swelling.

Conclusions

Presently available information indicates that the plasma membrane and mitochondria are the main targets for ultrasound treatment, and free radicals formation such as ·OH due to ultrasound cavitation may play an important role in mediating these cellular response processes. Moreover the mechanical effect might also be involved in inducing cell damage because there was significant mitochondria membrane potential loss and no visible ROS detection when cells were exposed to ultrasound for 30 s.
Neoplastic Lymphangiosis of the Upper Aerodigestive Tract Simulating Field Cancerization: Histopathological Analysis, Surgical Limits and Literature Review
Authors: Mattavelli Franco , Pizzi Natalia , Pennacchioli Elisabetta , Radaelli Stefano , Quattrone Pasquale , Mattavelli Davide , Fior Andrea , Pilotti Silvana
Published: February 2018

Neoplastic lymphangiosis is defined as extensive embolic spread of cancer cells in the lymphatic vessels often without any evidence of a mass. Instead, field cancerization is defined by the presence of multifocal neoplastic lesions in a mucosal field previously exposed to mutagenic factors. In this case report, this oncological entity was suggested by the wide extent and multifocality of the disease and by the patient's exposure to risk factors. Instead, the pathological slides revealed the integrity of the mucosa and the presence of widespread embolic metastasis to lymphatic vessels. Thus, the diagnosis was changed to neoplastic lymphangiosis. This clinical presentation is a negative prognostic factor, and surgical treatment is ineffective because of the impossibility to obtain adequate free margins. The present case underlines the poor prognosis of such locally advanced cancer and the importance of recognizing it early so that the treatment approach can be adapted.
Cancer Mortality in Italy, 2008, and Predictions for 2012
Authors: Rosso Tiziana , Malvezzi Matteo , Bertuccio Paola , Negri Eva , La Vecchia Carlo , Decarli Adriano
Published: February 2018

Aims and background

This report provides up-to-date data and statistics for cancer mortality in Italy in 2008, and predicts the figures and rates for selected cancer sites for 2012.

Methods

Cancer death certifications (for 30 sites) and resident population estimates in 2008 stratified by sex and age were obtained from the World Health Organization (WHO) database (WHOSIS). Mortality rates were age-standardized on the world standard population.

Results

Cancer deaths registered in Italy in 2008 were 172,783 (97,773 men and 75,010 women), corresponding to age-standardized death rates of 144.1/100,000 men and 84.3/100,000 women. The projected cancer deaths in 2012 are 178,000 (100,000 men, 78,000 women) and the corresponding rates 132,5/100,000 men and 80.5/100,000 women. The favorable trend in lung cancer mortality among men was confirmed, with rates of 37.7/100,000 in 2008 (all ages) and 33.3 for 2012. Other tobacco-related cancers also declined in men but not in women, including pancreatic cancer, whose rates tended to level off over the last 3 years. The fall in female cancer mortality rates continues to be led by favorable trends in breast cancer (16.1/100,000 in 2007 and 15.2 in 2012), intestinal cancer, stomach cancer and uterine cancer. However, the female lung cancer mortality was still rising with 7743 deaths in 2008 (9.5/100,000), and lung cancer is predicted to become the second cause of female cancer mortality by 2012 (8,500 deaths, 9.8/100,000).

Conclusions

Reduced tobacco and alcohol consumption are largely responsible for the favorable trends in cancer mortality in men. Advances in treatment and management accounted for the reduced mortality from colorectal cancer, breast cancer, leukemias and a few other cancers, as well as improved diagnosis for colorectal, cervical and breast cancer. The rising epidemic of tobacco-related deaths in women indicates the need for targeted tobacco-control strategies.
Image-Guided Positioning in Intracranial Non-Invasive Stereotactic Radiosurgery for the Treatment of Brain Metastasis
Authors: Dincoglan Ferrat , Beyzadeoglu Murat , Sager Omer , Oysul Kaan , Sirin Sait , Surenkok Serdar , Gamsiz Hakan , Uysal Bora , Demiral Selcuk , Dirican Bahar
Published: February 2018

Aims and background

The aim of the study was to examine the feasibility of non-invasive image-guided radiosurgery to improve patient comfort and quality of life in stereotactic radiosurgery planning and treatment of patients with brain metastasis. Precise immobilization is a rule of thumb for stereotactic radiosurgery. Non-invasive immobilization techniques have the potential of improved quality of life compared with invasive procedures.

Methods and study design

A total of 92 lesions from 42 patients with brain metastasis were included in the study. After immobilization with a thermoplastic mask and a bite-block unlike the invasive frame-based procedure, planning computed tomography images were acquired and fused with magnetic resonance images. After contouring, intensity-modulated stereotactic radiosurgery (IM-SRS) planning was done, and the patients were re-immobilized on the treatment couch for the therapy procedures. While patients were on the treatment couch, kilovoltage-cone beam computed tomography images were acquired to determine setup errors and achieve on-line correction and then repeated after on-line correction to confirm precise tumor localization. The patients then underwent single-fraction definitive treatment.

Results

For the 92 lesions treated, mean ± SD values of translational setup corrections in X (lateral), Y (longitudinal), and Z (vertical) dimensions were 0.7 ± 0.7 mm, 0.8 ± 0.7 mm, and 0.6 ± 0.5 mm, and rotational set-up corrections were 0.5 ± 1.1°, 0.06 ± 1.1°, and -0.1 ± 1.1° in X (pitch), Y (roll), and Z (yaw), respectively. The mean three-dimensional correction vector was 1.2 ± 1.1 mm.

Conclusions

Non-invasive image-guided radiosurgery for brain metastasis is feasible, and the non-invasive treatment approach can be routinely used in clinical practice to improve patientís quality of life.
Looking at Differences in Stage and Treatment of Colorectal Cancers across Italy: A EUROCARE-5 High Resolution Study
Authors: Minicozzi Pamela , Caldarella Adele , Giacomin Adriano , de Leon Maurizio Ponz , Cesaraccio Rosaria , Falcini Fabio , Fusco Mario , Iachetta Francesco , Pellegri Carlotta , Tumino Rosario , Capocaccia Riccardo , Sant Milena
Published: February 2018

Aims and background

The high incidence and the estimate of a five-year relative survival of 59% for colorectal cancer in Italy were the main reasons to investigate the management of Italian patients with colorectal cancer diagnosed in the early 2000s.

Methods

Samples of adult (≥15 years) patients diagnosed in 2003–2005 with a colorectal cancer were randomly selected in 8 Italian population-based cancer registries. The z test was used to evaluate differences in proportions of Dukes stage, patients with at least 12 examined lymph nodes, and of cases treated with curative surgery plus chemotherapy or plus radiotherapy and diagnosed with colon or rectal tumors, respectively. Logistic regression models were used to estimate odds ratios of receiving the selected treatment in each cancer registry, age group and stage category, by anatomical subsite.

Results

A total of 3,938 colorectal cancer patients were analyzed. About 40% of the cases were over 75 years of age at diagnosis and at Dukes A + B stages. Higher proportions of early stages were found in the northern cancer registries. High percentages of resection with a curative intent were observed in Reggio Emilia (northern Italy), in 15 to 74-year-old patients, and at Dukes B stage. At least 12 lymph nodes were more frequently examined in the north of the country. After adjusting for age and stage, no significant differences were seen in the odds ratios of receiving surgery plus chemotherapy between cancer registries, whereas surgery plus radiotherapy was more frequent in Napoli (southern Italy) and less frequent in Biella (northern Italy).

Conclusions

Some disparities in staging and treatment of colorectal cancer patients persist across Italy. National oncological plans still need to reduce inequalities in provision and access to proper care.
Neoadjuvant Therapy and Mini-Invasive Total Mesorectal Excision for Rectal Cancer: Feasibility and Outcome Analysis from a Single Institution Prospectively Collected Data Base
Authors: Grosso Federica , Mandalà Mario , Maglione Valeria , Berretta Laura , Mariani Narciso , Rossi Maura , Piovano Pier Luigi , Drago Domenico , Summa Massimo , Franzone Paola , Musante Francesco , Spinoglio Giuseppe
Published: February 2018

Aim and background

Neoadjuvant treatment for rectal adenocarcinoma improves local control and represents the standard for locally advanced disease. Laparoscopic and robotic total mesorectal excision has been increasingly adopted. It provides magnified visualization of the pelvic cavity, thereby facilitating the mesorectal dissection.

Methods

Consecutive patients with locally advanced/ultralow rectal adenocarcinoma received neoadjuvant treatment and mini-invasive total mesorectal excision at our center. We retrospectively reviewed the clinical records by using a prospectively collected data base and focusing on feasibility, tumor response and treatment outcomes.

Results

In a 13-year period, 117 rectal adenocarcinoma patients (80 males and 37 females) received neoadjuvant treatment and mini-invasive total mesorectal excision. Median age at diagnosis was 67 years; pre-treatment stage was I in 10 (9%); IIA in 58 (50%); IIC in 5 (4%); IIIA in 10 (9%); IIIB in 31 (26%) and IV in 3 (2%) patients. All patients received external beam radiation therapy, 79 (67%) combined with fluorouracil-based chemotherapy. One-hundred and three patients underwent laparoscopic surgery and 14 robotic surgery. Overall, 90 patients (77%) had anterior resection and 27 (23%) had abdominoperineal resection. Down-staging was obtained in 70 patients (66%). No major intraoperative nor delayed surgical complications were observed. At a median follow up of 52 months, 8 patients (7%) had a local relapse, 7 of them along with distant relapse, and 16 (14%) had distant relapse. The 5-year relapse-free survival was 76.5%.

Conclusions

Our data suggest that in a community hospital mini-invasive surgery after neoadjuvant treatment is feasible in real clinical practice and achieves consistent results in term of disease control rate.
From a Waiting List to a Priority List: A Computerized Model for an Easy-to-Manage and Automatically Updated Priority List in the Booking of Patients Waiting for Radiotherapy
Authors: Scoccianti Silvia , Agresti Benedetta , Simontacchi Gabriele , Detti Beatrice , Cipressi Samantha , Iannalfi Alberto , Marrazzo Livia , Mangoni Monica , Paiar Fabiola , Livi Lorenzo , Biti Giampaolo
Published: February 2018

Aims and background

Waiting time for radiotherapy is a major problem in clinical practice. We developed a model to create a priority list of patients waiting for radiotherapy according to clinical criteria, where booking of patients is not on a “first-come, first-served” basis and where prioritization has not been left up to individual discretion.

Methods

The system is based on an algorithm that assigns to each patient a personal code (priority code, PC) that can be used as a continuous variable to have a priority list. PCpatient = D0patient + PWTsubgroup of treatment. Palliative treatments were categorized according to the clinical urgency. Radical treatments were stratified by primary tumors, by the setting of treatment (preoperative, curative, postoperative) and by the main prognostic factors. Each subgroup of patients has a “priority waiting time” (PWT subgroup of treatment). Calculation of the PC starts from a differentiated date according to clinical scenario [Reference date (D0)], which is taken from the clinical history of the patient.

Results

Patients are differentiated according to clinical criteria and according to time elapsed from diagnosis. The priority list can be automatically updated day by day. Delays in patient referral or imaging availability are minimized.

Conclusions

The model represents a tool for an objective and automatic prioritization of the patients who are waiting for radiotherapy.
Outcome Evaluation in Pre-Trastuzumab Era between Different Breast Cancer Phenotypes: A Population-Based Study on Italian Women
Authors: Cortesi Laura , De Matteis Elisabetta , Cirilli Claudia , Marcheselli Luigi , Proietto Manuela , Federico Massimo
Published: February 2018

Aims and background

Based on estrogen receptor (ER), progesterone receptor (PgR) and Her2/neu (HER2) expression, four breast cancer subtypes have been distinguished: luminal A (ER and/or PgR/HER2–, Ki67 <14%), luminal B (ER and/or PgR/HER2–, Ki67 ≥14% or ER and/or PgR/HER2), triple-negative (ER-/PgR-/HER2–), and HER2 (ER-/PgR-/HER2). Our aim was to evaluate the prognosis of these phenotypes in the pre-trastuzumab era in a large cohort of Italian women.

Methods and study design

We studied 2347 breast cancer patients, in stage I-II, registered by the Modena Cancer Registry from 1999 to 2006 in the Modena province, Italy. Overall survival, disease-free survival and second non-mammary tumors were evaluated.

Results

A total of 1868 luminal A (79.6%), 195 luminal B (8.3%), 205 triple-negative (8.7%) and 79 HER2 (3.4%) patients were identified. A better prognosis was observed for luminal A than for luminal B, HER2 and triple-negative subtypes (5-year overall survival, 91% vs 89% vs 87% vs 86%, respectively, P <0.001). Disease-free survival for pT1a and pT1b tumors was worse in HER2 (82%) than in triple-negative (90%), luminal B (95%) and luminal A (97%) (P = 0.013). Finally, luminal B patients had a significantly higher rate of second non-mammary tumors than the other groups.

Conclusions

In the pre-trastuzumab era, luminal A patients showed a better 5-year overall survival than luminal B, HER2 and triple-negative patients, but in terms of disease-free survival, HER2 subtype represented an unfavorable group over time, whereas the triple-negative group had an increased risk of relapse in the first 42 months and then decreased. Among each prognostic factor, ER <10%, Ki67 >14% and HER2 overexpression are considered as risk factors, but only HER2 positivity seems to preserve the role over time.
Brain Metastases in Breast Cancer: Analysis of the Role of HER2 Status and Treatment in the Outcome of 94 Patients
Authors: Fokas Emmanouil , Henzel Martin , Hamm Klaus , Grund Steffen , Engenhart-Cabillic Rita
Published: February 2018

Aims and background

We investigated the impact of human epidermal growth factor receptor 2 (HER2) and prognostic factors in the outcome of patients with breast cancer that developed brain metastases.

Methods

The data from 94 patients who received multidisciplinary therapy from 2001 to 2007 were retrospectively reviewed. Patients were assigned according to their HER2 status, and overall survival and time to brain metastases recurrence/progression were evaluated. The prognostic value of age, presence of extracerebral metastases, recursive partitioning analysis class, hormone therapy, systemic therapy and trastuzumab was assessed.

Results

The median overall survival and time to brain disease progression were 7.1 and 6.5 months, respectively. HER2 positivity (P = 0.006), treatment with trastuzumab (P = 0.025), chemotherapy (P = 0.011) and recursive partitioning analysis class I-II (P <0.001) were associated with prolonged survival on univariate analysis. On multivariate analysis, only recursive partitioning analysis class I-II (P <0.001) and triple-negative disease (P = 0.04) remained significant for overall survival, whereas time to brain metastases progression was only associated with recursive partitioning analysis class I-II (P = 0.001). The time from the diagnosis of primary disease to brain metastasis was slightly shorter in the HER2+ patients than in HER2– patients (36 vs 39 months). Intensified local treatment of brain metastasis incorporating whole-brain radiotherapy and/or radiosurgery and neurosurgery did not affect survival. Patients with triple-negative disease presented a significantly lower survival than the rest of the cohort (4 vs 8 months; P = 0.012).

Conclusions

Recursive partitioning analysis class I-II was found to be the strongest independent predictive factor. Treatment with trastuzumab in HER2+ patients appeared to improve overall survival, probably due to the better control of systemic metastatic disease, but did not maintain significance in multivariate analysis. The dismal prognosis of patients with triple-negative breast cancer highlights the need to develop novel therapies to improve the poor survival.
Different methods of detaching adherent cells significantly affect the detection of TRAIL receptors
Authors: Zhang Bo , Shan Hong , Li Dan , Li Zheng-ran , Zhu Kang-shun , Jiang Zai-bo , Huang Ming-sheng
Published: February 2018

Aims and background

As a powerful technique allowing analysis of large numbers of cells, fluorescence-activated cell sorting (FACS) is used more and more widely. For FACS analysis, adherent cells are usually detached by trypsinization, followed by centrifugation and resuspension. However, trypsinization can cut off some receptors from the cell surface like fine scissors, which will affect the accuracy of FACS results. Though non-enzymatic methods such as citric saline buffer have been used to determine cell surface receptors, how much of the receptors is cut off by trypsinization has been rarely studied. This work aimed to investigate whether different methods of detaching adherent cells could affect the detection of cell surface receptors.

Methods

Human hepatocellular carcinoma cell lines (HepG2, Huh7 and Hep3B) were detached enzymatically with trypsin-EDTA solution or non-enzymatically with citric saline buffer, and then the receptors of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were detected by FACS analysis. Cell viability, cell cycle and apoptosis (sub-G1 fraction detected by FACS) of the trypsin-EDTA group and citric saline buffer group were also studied.

Results

Different methods of detaching adherent cells could significantly affect the detection of TRAIL receptors. Compared to the conventional trypsin-EDTA group, the non-enzymatic group showed a 3.42-fold increase in the mean fluorescence intensity index of DcR HepG2 and a 1.25-fold increase in DR Huh 7 (P <0.05). However, the viability, cell cycle and apoptosis of these cells were not affected.

Conclusions

Citric saline buffer might be recommended as the first choice to detach adherent cells for FACS analysis of cell surface receptors.
Up-regulation of p21WAF1/CIP1 by small activating RNA inhibits the in vitro and in vivo growth of pancreatic cancer cells
Authors: Zhang Zhiping , Wang Zhou , Liu Xiangyan , Wang Jie , Li Feng , Li Changling , Shan Baozhong
Published: February 2018

Aims and background

To study the inhibitory effect of p21WAF1/CIP1 activation by saRNA on the growth of human pancreatic cancer cells PANC-1 in vitro and in vivo.

Methods and study design

A dsRNA (dsP21) targeting the p21WAF1/CIP1 gene promoter at position-322 relative to the transcription start site was transfected into PANC-1 cells. Expression of mRNA and protein was evaluated by semiquantitative RT-PCR and Western blotting. Proliferation of PANC-1 cells was measured by the MTT method, and the apoptosis rate was detected by flow cytometry. PANC-1 cells were transplanted subcutaneously in nude mice, and the inhibitory effect of dsP21 on tumor growth was observed.

Results

The introduction of dsP21 was shown to efficiently up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells according to the results of RT-PCR and Western blotting (P <0.01, compared with controls). The inhibitory effect on cell proliferation was confirmed by the MTT test (P <0.05, compared with controls). The apoptosis rate of PANC-1 cells treated with dsP21 was significantly higher than that of the control cells (P <0.01). Our experimental data showed that dsP21-mediated up-regulation of p21 expression exerted an apparent growth inhibitory effect on PANC-1 cells in vivo.

Conclusions

dsP21 targeting the p21WAF1/CIP1 gene promoter can specifically up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells. It therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo and can be used as a new method and material for the gene therapy of pancreatic cancer.
Rare somatic mutation of pro-apoptotic BAX and BAK genes in common human cancers
Authors: Kim Min Sung , Kim Sung Soo , Yoo Nam Jin , Lee Sug Hyung
Published: February 2018

Aims and background

BAX and BAK are both pro-apoptotic Bcl-2 proteins and are essential for the pathway of intrinsic apoptosis. Apoptosis in cancer cells is frequently inactivated by somatic mutations. The aim of the study was to see whether somatic mutations of BAX and BAK genes are characteristics of common human cancers.

Methods

We analyzed somatic mutation of BAX and BAK genes in 47 gastric, 47 colorectal, 47 breast, 47 lung and 47 prostate carcinomas, and 47 acute leukemias by a polymerase chain reaction and single-strand conformation polymorphism assay.

Results

We identified BAX gene mutations in one colon (2.1%) and three gastric (6.4%) cancers. All of the mutations were frameshift mutations in the G8 repeat sequences and were detected in cancers with high microsatellite instability (36.4%). There was no evidence of BAX mutation in the other cancers, nor was somatic mutation of the BAK gene detected in the cancers.

Conclusions

Our data indicate that somatic mutation of BAX and BAK genes are rare in the common cancers (besides the cancers with high microsatellite instability) and suggest that neither BAX nor BAK mutation may causally be implicated in their tumorigenesis.
A Case Report of Metastatic Atypical Thymic Carcinoid with Ectopic ACTH Production: Locoregional Control after Adaptive Radiation Treatment
Authors: Valeriani Maurizio , Agolli Linda , Falco Teresa , Osti Mattia Falchetto , De Sanctis Vitaliana , Enrici Riccardo Maurizi
Published: February 2018

Thymic carcinoid is an extremely rare malignancy. This tumor is often associated with endocrine disorders such as Cushing's syndrome, multiple endocrine neoplasia type 1 and superior vena cava syndrome. We describe the case of a 44-year-old Italian woman with metastatic atypical thymic carcinoid secreting ectopic adrenocorticotropic hormone who was treated with adaptive radiation therapy with a curative dose schedule for a symptomatic mediastinal tumor. After 22 months, the patient was in good clinical condition, presenting stable disease without any evidence of local or systemic progression. To our knowledge there are no previously reported data regarding radical radiotherapy in the treatment of thymic carcinoids.
The “Don't Smoke in Our Home” Randomized Controlled Trial to Protect Children from Second-Hand Smoke Exposure at Home
Authors:   the Da noi non si fuma Study Group, Chellini Elisabetta , Gorini Giuseppe , Carreras Giulia
Published: February 2018

Aims and background

Increasing smoke-free homes is an important public health goal, but only few interventions have yielded positive results. The aim of the “Don't smoke in our home” trial was to evaluate a counseling intervention focused on promoting totally smoke-free homes and cars (TSFHC) delivered to women with children resident in four Tuscan towns.

Methods and study design

We used a two-group randomized controlled trial design. Participants were asked about their smoking habits and about restrictions on smoking in their homes and cars. All women received a self-help booklet promoting TSFHC, and 110 women randomized to the intervention also attended brief counseling on second-hand smoke exposure protection and received three gifts to remember the commitment to TSFHC. Follow-up was conducted by phone after four months.

Results

We recruited 218 women, 64 of whom had a university degree and 131 of whom were smokers; 62% reported smoking indoors and 58% in cars. Before the intervention, nonsmokers were more likely to report totally smoke-free homes (TSFH, 52%) and cars (TSFC, 53%) than smokers (26% and 17% respectively; P <0.001). Participants of the experimental arm had similar odds as controls of having implemented TSFH after the intervention, and nonsignificantly increased odds of having introduced TSFC (odds ratio [OR] 1.47; 95% confidence interval [CI] 0.69–3.11), particularly among smokers (OR 2.24, 95%CI 0.69–7.26). All participants independently of the study arm recorded significant increases of 12 and 15 percentage points in TSFH and TSFC, respectively. Few smokers quit smoking (7%), stopped smoking indoors (5%), and stopped smoking in cars (7%), with no differences between the intervention and control groups.

Conclusions

Adding brief counseling to written materials did not significantly increase TSFHC. However, delivering written materials only may produce modest but noteworthy TSFHC increases at the population level, even though the participants in the study did not represent a population-based sample, given the high proportion of highly educated women. Further studies are required to confirm these results.