bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic Resonance Imaging in Local Staging of Endometrial Carcinoma: Diagnostic Performance, Pitfalls, and Literature Review
Authors: Zandrino Franco , La Paglia Ernesto , Musante Francesco
Published: February 2018

Aims and background

To assess the diagnostic accuracy of magnetic resonance imaging in local staging of endometrial carcinoma, and to review the results and pitfalls described in the literature.

Methods

Thirty women with a histological diagnosis of endometrial carcinoma underwent magnetic resonance imaging. Unenhanced T2-weighted and dynamic contrast-enhanced T1-weighted sequences were obtained. Hysterectomy and salpingo-oophorectomy was performed in all patients. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for the detection of deep myometrial and cervical infiltration.

Results

For deep myometrial infiltration T2-weighted sequences reached a sensitivity of 85%, specificity of 76%, PPV of 73%, NVPof 87%, and accuracy of 80%, while contrast-enhanced scans reached a sensitivity of 90%, specificity of 80%, PPV of 82%, NPV of 89%, and accuracy of 85%. For cervical infiltration T2-weighted sequences reached a sensitivity of 75%, specificity of 88%, PPV of 50%, NPV of 96%, and accuracy of 87%, while contrast-enhanced scans reached a sensitivity of 100%, specificity of 94%, PPV of 75%, NPV of 100%, and accuracy of 95%.

Conclusions

Unenhanced and dynamic gadolinium-enhanced magnetic resonance allows accurate assessment of myometrial and cervical infiltration. Information provided by magnetic resonance imaging can define prognosis and management.
[11C]choline-PET-guided Helical Tomotherapy and Estramustine in a Patient with Pelvic-Recurrent Prostate Cancer: Local Control and Toxicity Profile after 24 Months
Authors: Alongi Filippo , Schipani Stefano , Gajate Ana Maria Samanes , Rosso Alberto , Cozzarini Cesare , Fiorino Claudio , Alongi Pierpaolo , Picchio Maria , Gianolli Luigi , Messa Cristina , Di Muzio Nadia
Published: February 2018

[11C]choline positron emission tomograhy can be useful to detect metastatic disease and to localize isolated lymph node relapse after primary treatment in case of prostate-specific antigen failure. In case of lymph node failure in prostate cancer patients, surgery or radiotherapy can be proposed with a curative intent. Some reports have suggested that radiotherapy could have a role in local control of oligometastatic lymph node disease. This is the first reported case of [11C]choline positron emission tomography-guided helical tomotherapy concomitant with estramustine for the treatment of pelvic-recurrent prostate cancer. At 24 months after the end of helical tomotherapy, prostate-specific antigen was undetectable and no late toxicities were recorded. A disease-free survival of 24 months, in the absence of any type of systemic therapy, is uncommon in metastatic prostate cancer. The therapeutic approach of the case report is discussed and a literature review on the issue is presented.
Intensity-Modulated Radiation Therapy with Simultaneous Integrated Boost in Unresected Left-Sided Pleural Mesothelioma: A Case Report
Authors: Cilla Savino , Digesù Cinzia , Silvano Giovanni , Macchia Gabriella , Massaccesi Mariangela , Deodato Francesco , DA Padula Gilbert , Fidanzio Andrea , Piermattei Angelo , Morganti Alessio G
Published: February 2018

A 77-year-old male patient with unresected malignant pleural mesothelioma, clinical stage T3N0M0 according to the New International Staging System for Diffuse Malignant Pleural Mesothelioma, received intensity-modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) after 6 cycles of chemotherapy with cisplatin and pemetrexed. SIB-IMRT delivered 40.5 Gy (1.5 Gy/fraction) to the left pleura and 50 Gy (1.85 Gy/fraction) to the sites of macroscopic disease. Radiotherapy was well tolerated. Two months after the end of radiotherapy the patient showed grade 2 lung toxicity (febrile episodes accompanied by dry cough) that was successfully treated with steroid therapy. Local control lasted for 2 years after SIB-IMRT. Then the tumor recurred marginally to the radiation field and the patient underwent chemotherapy with pemetrexed. Three years from the diagnosis, the patient is alive and in good general condition. He only takes prednisone 5 mg/daily for exertional dyspnea. To the best of our knowledge this is the first reported use of SIB-IMRT in unresected malignant pleural mesothelioma. Considering the dosimetric advantages of SIB-IMRT and the clinical results observed in our patient, additional evaluation of this technique seems justified.
No Implication of Simian virus 40 in pathogenesis of Malignant Pleural Mesothelioma in Slovenia
Authors: Hmeljak Julija , Kern Izidor , Cör Andrej
Published: February 2018

Background and aim

Malignant mesothelioma is predominantly caused by asbestos exposure, although the association of Simian virus 40 in its pathogenesis is currently still under debate. Simian virus 40, a DNA rhesus monkey virus with oncogenic properties, accidentally contaminated early batches of polio vaccine in the 1960s. In the 1990s, viral sequences and proteins were discovered in several human tumors, which triggered research to find a link between Simian virus 40 and human cancers, especially malignant mesothelioma. The aim of our study was to establish an effective laboratory procedure for Simian virus 40 detection and to investigate the presence of Simian virus 40 DNA and small t antigen in mesothelioma samples from Slovenian patients.

Methods and study design

Paraffin-embedded malignant pleural mesothelioma specimens from 103 Slovenian patients were collected and used for total DNA isolation and real-time polymerase chain reaction for Simian virus 40 small t and large T DNA analysis. Special attention was devoted to primer design, good laboratory practice and polymerase chain reaction contamination prevention. Polymerase chain reaction products were sequenced and BLAST aligned. One 5 μm thick paraffin section from each patient's tissue block was stained with hematoxylin and eosin for histological typing and one for immunohistochemical detection of Simian virus 40 small t antigen using a monoclonal antibody against Simian virus 40 (Pab280). SV40-expressing Wi-38 cells were used as positive control in both PCR and immunohistochemistry.

Results

In real-time polymerase chain reaction analyses, only 4 samples gave products with primer pairs amplifying small t antigen and were inconsistent and poorly reproducible. BLAST alignment showed no homology with any deposited SV40 sequences. No immunopositive staining for SV40 small t antigen was found in any of the samples.

Conclusions

We found no evidence of SV40 presence in tissue samples from 103 Slovenian patients with malignant pleural mesothelioma. Asbestos exposure remains the main risk factor for malignant pleural mesothelioma in Slovenia. Free full text available at www.tumorionline.it
Influence of Stage Discrepancy on Outcome in Patients Treated with Radical Cystectomy
Authors: Ku Ja Hyeon , Moon Kyung Chul , Kwak Cheol , Kim Hyeon Hoe
Published: February 2018

Aims and background

To evaluate the influence of stage discrepancy on clinical outcome in patients with bladder cancer who have undergone radical cystectomy.

Methods and study design

We reviewed the records of 155 patients who had undergone radical cystectomy. Of the 155 patients (128 males, 27 females), 68 had clinical nonmuscle invasive disease and 87 had muscle invasive disease. Follow-up ranged from 1.0 to 162.4 months (median, 34.3).

Results

There was no significant difference in overall survival according to clinical T stage (P = 0.483). However, the actuarial overall survival rate of the pathological muscle invasive disease group was significantly less than that in the pathological nonmuscle invasive disease group (P <0.001). Multivariate analysis with the Cox regression model revealed that lymphovascular invasion (P = 0.001, relative risk [RR] = 2.463) and pathological T stage (P = 0.003, RR = 3.148) were strongly associated with overall survival. There was no difference in cancer-specific survival according to clinical T stage (P = 0.455). However, cancer-specific survival rate of the pathological muscle invasive disease group was significantly less than that in the pathological nonmuscle invasive disease group (P <0.001). Multivariate Cox proportional hazards model analysis showed that lymphovascular invasion (P = 0.001, RR = 2.545) and pathological T stage (P = 0.002, RR = 3.823) were independent predictors of cancer-specific survival.

Conclusions

Our findings indicate that clinical stage determined by transurethral resection is not predictive of clinical outcome after radical cystectomy in patients with bladder cancer. Free full text available at www.tumorionline.it
Preoperative Radiotherapy and Concurrent Chemotherapy with Bolus 5-Fluorouracil for Rectal Cancer: A Prospective Analysis of 98 Patients
Authors: Wygoda Marc , Rottenberg Yakir , Kadouri Luna , Pikarsky Alon , Hubert Ayala
Published: February 2018

Aims and background

Surgical resection of rectal cancer is associated with a high pelvic recurrence rate. Preoperative large-fraction radiotherapy (RT) with a short interval after local excision has been associated with a significant improvement in locoregional recurrence rates and overall survival, but with high rates of toxicity. We here present the results of our combined-modality treatment protocol for patients with locally advanced rectal cancer.

Methods

Between September 1999 and June 2005, 98 patients were prospectively entered into the protocol. Eligibility criteria included any of the following: cT3-4 disease, clinically positive lymph nodes, or tumor located less than 6 cm from the anal verge. RT was delivered with a three-field technique to a dose of 45 Gy, plus an optional 5.4–9 Gy boost. Chemotherapy, administered concomitantly with RT, consisted of bolus 5-fluorouracil (5-FU) 500 mg days 1–5 followed by 5-FU 600 mg/m2 and leucovorin 50 mg on days 16, 23, 30 and 37. Surgery was performed 6–8 weeks after RT completion and was followed by 8 courses of 5-FU 900 mg/m2 and leucovorin 100 mg/m2 every 14 days.

Results

Low anterior resection was performed in 64.5% of the patients and in 38.8% of those with tumors located less than 6 cm from the anal verge. All patients except one had clear pathological margins, 68.8% had negative nodes, and pathological complete response was seen in 13.5%. With a median follow-up of 31.5 months, 3 patients (3.0%) had locoregional recurrence, 19 (19.3%) developed distant metastasis, and 10 patients (10.1%) died. The estimated median disease-free survival was 70.6 months. Grade 3 or 4 gastrointestinal toxicity was seen in 24.5% of the patients and 3.0% had neutropenic fever. One fatal toxicity occurred during treatment.

Conclusions

Our results suggest that our combined-modality treatment protocol is well tolerated and achieves high locoregional control in this unselected population. The overall survival results are also encouraging. Further studies are required to confirm the toxicity profile and survival results of this regimen. Free full text available at www.tumorionline.it
Effect of microRNA-206 on Cytoskeleton Remodelling by Downregulating Cdc42 in MDA-MB-231 Cells
Authors: Liu Hao , Cao You-De , Ye Wei-Xia , Sun Yang-Yang
Published: February 2018

Aims and background

MicroRNAs are small, noncoding, single-stranded RNAs that regulate gene expression post-transcriptionally. miR-206 is known to play an important role in breast cancer metastasis. When we sought to predict the target of miR-206 by Targetscan, Pictar and miRanda, we found Cdc42 was a potential one. In this study, we transfected miR-206 into MDA-MB-231 cells and examined Cdc42 protein expression as well as MMP-2 and MMP-9, which are also associated with metastasis of breast cancer. Since Cdc42 is involved in filopodia and invadopodia formation, we examined the morphological changes of MDA-MB-231 cells.

Methods and study design

miR-206 mimics were transfected into MDA-MB-231 cells using Lipofectamine™ 2000. Protein expression was detected by Western blot. Cells were stained with FITC-phalloidin to visualize F-actin. Invasive ability and migratory ability were examined by invasion assay and migration assay in vitro.

Results

Cdc42, MMP-2 and MMP-9 were downregulated on the protein level. The formation of filopodia, which requires Cdc42, was inhibited in miR-206 transfected cells, even under the stimulation of EGF. The invasion and migration of MDA-MB-231 cells in vitro was inhibited by miR-206 too.

Conclusions

The results suggest that miR-206 may suppress invasion and migration of MDA-MB-231 cells in vitro partly via regulating actin cytoskeleton remodelling such as filopodia formation. Free full text available at www.tumorionline.it
Long-lasting Response with Metronomic Capecitabine in Advanced Hepatocellular Carcinoma
Authors: Ballardini Pierluigi , Marri Ivan , Margutti Guido , Aliberti Camillo , Benea Giorgio , Manfredini Roberto
Published: February 2018

Effective and safe systemic treatment for advanced hepatocellular carcinoma (HCC) with severe underlying cirrhosis is not yet available. Sorafenib, an oral multikinase inhibitor, has proved to be effective in the treatment of patients affected by HCC with Child-Pugh class A liver function. For patients with cirrhosis-associated HCC having Child-Pugh class B and C liver function, no systemic treatments of documented efficacy and safety exist. We report a case of metastatic HCC associated with Child-Pugh class B cirrhosis that was treated with low, “metronomic” doses of capecitabine (1000 mg/day continuously). This treatment was effective and well tolerated and the response was maintained for 18 months. Metronomic capecitabine may represent a possible alternative in the treatment of those patients with advanced cirrhosis-associated HCC who cannot be treated with sorafenib. Free full text available at www.tumorionline.it
Chemopotentiation by Ultrafractionated Radiotherapy in Glioblastoma Resistant to Conventional Therapy
Authors: Jahraus Christopher D , Friedman Allan H
Published: February 2018

Introduction

Induced radiation resistance (IRR) and hyper-radiosensitivity (HRS) are well-described phenomena in basic literature, yet few reports have been published in which such phenomena are exploited clinically for the benefit of patients. Glioblastoma is a prime example.

Case and methods

The case of an 82-year-old woman is described whose resected frontoparietal glioblastoma progressed through treatment administered according to standard methods. With review board and patient approval, we continued her treatment using radiotherapy and temozolomide, but drastically modified the radiotherapy fractionation, administering 50 cGy twice daily on each of the first 5 days of a 14-day cycle. Temozolomide was administered on the first 4 days of each cycle. We use the term “ultrafractionated radiotherapy” to refer to the extremely low doses of radiation used in this case.

Results

This modified regimen resulted in regression of the contrast-enhancing areas of disease recurrence identified on MRI, and the patient survived approximately 6 months following recurrence of her disease, having received 5 cycles of additional therapy after prior full-dose treatment.

Conclusions

Ultrafractionated radiotherapy and concurrent temozolomide were efficacious and tolerable in this patient whose glioblastoma previously progressed through conventional treatment. Additional studies of this approach are warranted. Free full text available at www.tumorionline.it
1. Neuroendocrine Tumors (NETs): Historical Overview and Epidemiology
Authors: Öberg Kjell
Published: February 2018

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms which take origin from the neuroendocrine cell system and are characterized by embryological, biological and histopathological differences. Traditionally considered as a rare and “niche” pathology, over the last decades they have gained significant attention from the scientific community, even because of their increasing incidence and prevalence probably imputable to the availability of more sensitive diagnostic tools and to the development of higher awareness among clinicians. This paper retraces the key events that led to the discovery, characterization and classification of NETs as well as to the development of adequate treatment strategies. Incidence and epidemiology are also addressed. Free full text available at www.tumorionline.it
3. The ENETS Guidelines: The New TNM Classification System
Authors: Rindi Guido
Published: February 2018

The WHO definition of the 3 classes of well differentiated endocrine tumor, well differentiated endocrine carcinoma and poorly differentiated carcinoma, allows an efficient general classification of GEP NETs fitting European Union (EU) current clinical use. The ENETS grading and TNM staging systems are complementary tools allowing to improve patients’ stratification, and their adoption is strongly recommended. However, the prognostic value of these tools is still under investigation and more data are needed to support their usefulness at all gut sites and in perspective series. Similarly, the four classes system adopted by the WHO for the endocrine tumors of the lung allows a prognostically effective stratification of patients. A common grading system is advocated for lung and GEP NETS. Free full text available at www.tumorionline.it
5. Imaging techniques in diagnostic approaches
Authors: De Angelis Claudio G , Crippa Flavio
Published: February 2018

Despite the considerable technological advances in imaging modalities which have occurred over the last years, EUS remains one of the most reliable and accurate technique for the study of gastroenteropancreatic neuroendocrine tumors. More specifically, EUS can detect very small lesions, assess the local extent and lymph node involvement and biopsy the lesion for cytophatological confirmation (EUS-FNA). In addition, nuclear medicine imaging has a relevant role in the evaluation of NET. However, its performance depends on series of patient-specific features (lesion size and uptake, depth and other anatomic features; metabolic activity, receptor expression, affinity and vacancy, tissue specificity) and technical features (choice of tracer, administered dose, and physical half-life; instrument sensitivity, acquisition technique, reader experience). In particular, current data show that PET/CT has greater intrinsic resolution and sensitivity than SPECT or SPECT/CT images resulting in improved tumor detection. However, the PET tracer of choice has not yet been identified. 18F-FDG has proved to be useful as indicator of tumor aggressiveness rather than detection of extent of disease, and 68Ga-DOTA-TOC has demonstrated good results in clinical trials. 11C-5HTP has performed well in limited trials, but the 20-min half life of 11C precludes widespread availability. Better information concerning biodistribution and further comparative data of these agent in larger clinical trials are warranted. Free full text available at www.tumorionline.it
Lymph Node Harvesting in Colorectal Carcinoma Specimens
Authors: Lagoudianakis Emmanuel , Pappas Apostolos , Koronakis Nikolaos , Tsekouras Dimitrios , Dallianoudis John , Kontogianni Panagiota , Papanikolaou Dimitrios , Chrysikos John , Karavitis George , Markogiannakis Haridimos , Filis Konstantinos , Manouras Andreas
Published: February 2018

Introduction

Adequate lymph node evaluation is an important determinant of prognosis in patients with colorectal cancer. Current guidelines recommend evaluation of at least 12 lymph nodes; however, a significant number of patients fail to meet these criteria.

Aim

To investigate the factors that influence adequate recovery and evaluation of lymph nodes in colorectal cancer

Methods

We retrospectively analyzed 454 consecutive cases of colorectal cancer surgically treated from September 2000 to September 2006. Univariate and multivariate linear and logistic regression analysis was used to study the effect of various factors in lymph node recovery.

Results

The number of lymph nodes retrieved ranged from 0 to 62 with a median of 13 nodes. Overall, 189 (41.6%) patients had fewer than 12 nodes removed. Patient age, tumor stage, location and size were associated with lymph node retrieval. Multivariable regression revealed that the aforementioned variables, including gender and hospital type, explained 17% of the observed variance of the lymph node number.

Conclusion

Patient and tumor characteristics, although important, are only partly responsible for the variation of lymph node yield. Quality of surgical resection and/or the thoroughness of examination of the tissue by the pathologist might explain the wider proportion of this variance. Training in colorectal node evaluation could help to improve the quality of cancer care. Free full text available at www.tumorionline.it
Effectiveness of Interferon-Beta Therapy for Recurrent Glioblastoma: A Case Report
Authors: Utsuki Satoshi , Oka Hidehiro , Miyajima Yoshiteru , Sato Kimitoshi , Shimizu Satoru , Suzuki Sachio , Fujii Kiyotaka
Published: February 2018

Aims and background

Glioblastoma has a poor prognosis, with few therapeutic options if it recurs. We report a case in which we were able to inhibit the growth of a recurrent glioblastoma by weekly single-dose administration of interferon-beta.

Case report

A patient with recurrent glioblastoma after radiation and chemotherapy was treated with nimustine and interferon-beta. After 2 cycles of nimustine, the patient's leukocyte, neutrophil, and platelet counts showed grade 4 toxicity according to the National Cancer Institute's Common Toxicity Criteria. The patient was treated with a weekly single dose of interferon-beta at 6 × 106 IU. The tumor showed no remarkable changes after 18 months, and the patient's Karnofsky performance status remained at 50%.

Conclusions

The administration of interferon-beta produced long-term control in one case of glioblastoma and may be an effective therapy. Free full text available at www.tumorionline.it
Precursor B-cell Acute Lymphoblastic Leukemia after Thymoma and Myasthenia Gravis: Report of a Case and Review of the Literature
Authors: Chang Hung , Chen Tong-Jong , Chuang Wen-Yu , Lin Tung-Liang
Published: February 2018

The association of thymoma, myasthenia gravis (MG) and pure red cell aplasia (PRCA) is well recognized. The association of T-cell lymphoblastic lymphoma and thymoma/MG/PRCA is less distinctive but reported occasionally. We present a 35-year-old female patient who was diagnosed with thymoma and myasthenia gravis. She underwent a thymectomy shortly after the diagnosis. One year later she developed precursor B-cell acute lymphoblastic leukemia (ALL). Complete remission was achieved after induction chemotherapy but the disease relapsed and she expired two years after the diagnosis of ALL despite allogeneic stem cell transplantation. This association has never before been reported and the pathogenesis needs to be clarified. Aberrant thymus function in myasthenia gravis, immunosuppressive therapy and thymectomy are considered to account for the leukemia development in this patient. Free full text available at www.tumorionline.it
Infantile Fibrosarcoma: Retrospective Analysis of Eleven Patients
Authors: Akyüz Canan , Küpeli Serhan , Varan Ali , Gedikoglu Gökhan , Yalçin Bilgehan , Kutluk Tezer , Büyükpamukçu Münevver
Published: February 2018

Aims and background

Infantile fibrosarcomas are soft tissue sarcomas that are diagnosed at or soon after birth. In the present study, we retrospectively evaluated clinical characteristics, treatment modalities and outcome of patients diagnosed with infantile fibrosarcoma at our institution.

Methods

A retrospective review was conducted to evaluate demographic characteristics, presenting features, type and timing of surgery, other treatment modalities and survival characteristics.

Results

Nine males and 2 females were diagnosed with infantile fibrosarcoma between 1970–2008. The initial surgical procedure was subtotal resection in 4 patients, gross-total resection in 3 and biopsy in 4. Neoadjuvant chemotherapy was given to 10 patients. Three patients died, one for the disease and 2 from complications of therapy. Eight patients are under follow-up with no evidence of disease for 1.3 to 13.5 years. None of the patients in the series underwent amputation.

Conclusions

Owing to the chemosensitive nature of the tumor and possibility of spontaneous regression, neoadjuvant chemotherapy should be considered to prevent extensive or mutilating surgery.
Interaction Effect between the Receptor for Advanced Glycation End Products (RAGE) and High-Mobility Group Box-1 (HMGB-1) for the Migration of a Squamous Cell Carcinoma Cell Line
Authors: Choi June , Lee Min Koo , Oh Kyoung Ho , Kim Yeon Soo , Choi Han Young , Baek Seung Kuk , Jung Kwang Yoon , Woo Jeong-Soo , Lee Seung Hoon , Kwon Soon Young
Published: February 2018

Aims and background

The receptor for advanced glycation end products (RAGE) is a multiligand cell surface receptor of the immunoglobulin superfamily and a newly recognized invasion-related gene. High mobility group box-1 (HMGB-1) is a 30-kD protein binding to RAGE and acting as a transcription-factor-like protein that regulates the expression of several genes. In this study, the interaction effect between RAGE and HMGB-1 on the migration of SCC7 cells was investigated along with the inhibitory effect of the drug nifedipine on this interaction effect.

Methods and study design

Ten surgical specimens from patients with squamous cell carcinoma (SCC) of the head and neck and a SCC7 cell line were stained using immunohistochemical and immunocytochemical methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect RAGE expression in SCC7 cells; Western blot analysis was used to detect HMGB-1 expression in SCC7 cells. An in vitro migration assay (Boyden chamber migration assay) was used for evaluating the interaction effect between RAGE and HMGB-1 on the migration of SCC7 cells. HMGB-1 and various concentrations of nifedipine were tested for their effect on SCC7 cell migration with in vitro migration assays.

Results and conclusions

RAGE and HMGB-1 were expressed in almost all human head and neck SCC tissues and in SCC7 cells as detected by immunostaining. The migration assay showed that the interaction between RAGE and HMGB-1 increased SCC7 migration activity depending on the level of HMGB-1, and nifedipine inhibited the interaction effect between RAGE and HMGB-1 on SCC7 cells in a dose-dependent manner. The interaction between RAGE and HMGB-1 could be closely associated with metastasis of SCC of the head and neck. Nifedipine may have an inhibitory effect on tumor metastasis.
Multidisciplinary Approach in the Treatment of Malignant Paraganglioma of the Glomus Vagale: A Case Report
Authors: Milia Maria Elisa , Turri Lucia , Beldì Debora , Deantonio Letizia , Pareschi Roberto , Krengli Marco
Published: February 2018

Malignant paraganglioma of the glomus vagale is a rare tumor entity originating from paraganglia or glomus cells. It typically affects middle age. It differs from benign paraganglioma because of its rapid growth and more aggressive clinical behavior. We report the case of a 40-year-old man presenting with a 5 cm lesion in the upper right cervical region detected by computed tomography (CT) and magnetic resonance imaging (MRI), which also showed enlargement of ipsilateral spinal and jugulodigastric lymph nodes with contrast enhancement. Clinical manifestations at diagnosis included a partial neurological deficit involving the right cranial nerves X, XI and XII. Tumor vascularization was assessed by digital angiography. The tumor mass was entirely removed by a right cervical approach with en-bloc resection with the regional lymph nodes. Histopathological examination showed a paraganglioma with cellular pleomorphism, necrotic microfoci, perineural infiltration and angiogenesis. Massive metastases in two of three jugulodigastric and one spinal lymph nodes on the right side were also detected. Postoperative workup included MRI, positron emission tomography (PET)/CT, meta-iodine-benzyl-guanidine (MIBG) scan, liver ultrasound and chest radiography. Subsequently, the patient underwent conformal radiotherapy with concomitant cisplatin administration. At the last clinical and radiological follow-up examination 5 years after completion of treatment, the patient was free of tumor recurrence.

The integrated treatment by surgery and chemoradiation was feasible and effective in the management of this rare case of malignant paraganglioma of the glomus vagale. Multicenter studies should be done to increase the knowledge of tumor presentation and natural history and to analyze the possible treatment options.
Distribution of Coding Apoptotic Gene Polymorphisms in Women with Extreme Phenotypes of Breast Cancer Predisposition and Tolerance
Authors: Ulybina Yulia M , Kuligina Ekatherina S , Mitiushkina Nathalia V , Sherina Nathalia Y , Baholdin Dmitry V , Voskresenskiy Dmitry A , Polyakov Igor S , Togo Alexandr V , Semiglazov Vladimir F , Imyanitov Evgeny N
Published: February 2018

Aims and background

Comparison of subjects with extreme phenotypes of cancer susceptibility and tolerance allows to detect low-penetrance gene-disease interactions with a relatively small study size.

Methods and study design

We analyzed the distribution of 19 coding apoptotic gene polymorphisms (Bid Gly10Ser; Casp2 Leu141Val; Casp5 Ala90Thr and Val318Leu; Casp7 Glu255Asp; Casp8 His302Asp; Casp9 Val28Ala, His173Arg and Arg221Gln; Casp10 Ile479Leu; Faim Thr117Ala and Ser127Leu; DR4 Arg141His, Thr209Arg, Ala228Glu and Lys441Arg; Survivin Lys129Glu; TNFR1 Gln121Arg; XIAP Pro423Gln) in 121 breast cancer patients with clinical features of a hereditary predisposition (family history and/or early onset and/or bilaterality) and 142 elderly tumor-free women.

Results

None of the individual single nucleotide polymorphisms (SNPs) demonstrated an association with breast cancer risk. The analysis of gene interactions revealed that the combination of XIAP Pro423Gln (rs5956583) AA genotype with Casp7 Glu255Asp (rs2227310) CG genotype appeared to prevail in “supercases” relative to “supercontrols” (25/121 [21%] vs 11/142 [8%], P = 0.002). We attempted to validate this association in the second round of case-control analysis, which involved 519 randomly selected breast cancer patients and 509 age-matched healthy women, but no difference was detected upon this comparison.

Conclusions

Coding apoptotic gene polymorphisms do not play a major role in BC predisposition. The results of this investigation may be considered while designing future studies on breast cancer-associated candidate SNPs.
Trabectedin-Related Rhabdomyolysis: An Uncommon but Fatal Toxicity
Authors: Stoyianni Aikaterini , Kapodistrias Nikolaos , Kampletsas Eleutherios , Pentheroudakis George , Pavlidis Nicholas
Published: February 2018

Rhabdomyolysis is defined as the dissolution of striped muscle characterized by the leakage of intracellular muscle components into the circulation, which can ultimately lead to renal failure with a possible fatal outcome. Trabectedin is a potential cause of rhabdomyolysis. Herein, we describe a case of rhabdomyolysis in a female patient with recurrent metastatic leiomyosarcoma of the uterus and who had full recovery, and we review the already published cases in order to identify a common pattern of emergence.
Second-line chemotherapy with irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) in relapsed or metastatic gastric cancer: Lessons from clinical practice
Authors: Pistelli Mirco , Scartozzi Mario , Bittoni Alessandro , Galizia Eva , Berardi Rossana , Cascinu Stefano
Published: February 2018

Aims and background

Soon after the approval of irinotecan for second-line therapy of advanced gastric cancer, the FOLFIRI regimen represented a possible treatment choice in clinical practice. However, there was still scarce data on the efficacy of irinotecan in this setting. We retrospectively evaluated the efficacy of FOLFIRI as second-line treatment in advanced gastric cancer patients progressing after platinum-based chemotherapy.

Methods

Patients with metastatic gastric cancer progressing after platinum-based chemotherapy who received FOLFIRI as second-line chemotherapy were included in our analysis.

Results

Thirty patients were consecutively treated (20 males and 10 females). Median age was 62 years (range, 36–78). All patients had metastatic disease. In 17 cases (56.6%), peritoneal tumor diffusion was present. Six patients (20%) had previously received 5-fluorouracil-based adjuvant chemotherapy. The median number of cycles administered was 4 (range, 1–12). Partial remission was obtained in 1 case (3%) and stable disease in 8 patients (27%). Median progression-free survival and overall survival were 2.7 months and 5.5 months, respectively. The most common toxicities (grade 2–3) observed were neutropenia (13.3%), diarrhea (10%) and vomiting (30%). Ten patients (10%) received 3 or less courses of chemotherapy. In these cases, treatment was stopped before scheduled for accelerated worsening of clinical conditions.

Conclusions

FOLFIRI resulted scarcely active in metastatic gastric cancer patients pre-treated with platinum-based chemotherapy. In this setting, the real benefit of a second-line chemotherapy with the FOLFIRI regimen should be carefully re-considered, especially according to the clinical condition of the patient and possible treatment-related side effects.
Concurrent versus sequential administration of CMF chemotherapy and radiotherapy after breast-conserving surgery in early breast cancer
Authors: Kim Kyubo , Chie Eui Kyu , Han Wonshik , Noh Dong-Young , Oh Do-Youn , Im Seock-Ah , Kim Tae-You , Bang Yung-Jue , Ha Sung W
Published: February 2018

Aims and background

To compare the outcome of concurrent versus sequential administration of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy and radiotherapy after breast-conserving surgery in early breast cancer.

Methods

From February 1992 to January 2002, 156 patients underwent CMF chemotherapy and radiotherapy, either concurrently (CCRT group, 88 patients) or sequentially (SCRT group, 68 patients). There was a predilection of patients with a larger tumor (P = 0.0035), with more frequent nodal involvement (P = 0.0686), and younger age (P = 0.0776) in the CCRT group.

Results

The planned radiotherapy was completed in every patient. No grade 3 or 4 late treatment-related toxicity was observed in the CCRT or SCRT group. Compliance to the treatment as well as cosmetic outcome of the two groups were comparable. Despite more adverse factors for local-regional recurrence in the CCRT group, the 5-year local-regional control rate of the CCRT group was similar to that of the SCRT group (97.7% vs 93.8%, respectively, P = 0.1688). On multivariate analysis, concomitant administration of chemotherapy and radiotherapy was associated with improved local-regional control (P = 0.0463).

Conclusions

Concurrent administration of CMF chemotherapy and radiotherapy resulted in improved local-regional control over sequential administration without an increase in significant toxicity. Concurrent CMF chemoradiotherapy may serve as a viable option for patients at high-risk of local-regional relapse not suitable for anthracycline or taxane-based chemotherapy.
Larger tumor size predicts nodal involvement in patients with follicular thyroid carcinoma
Authors: Pisanu Adolfo , Deplano Daniela , Pili Michela , Uccheddu Alessandro
Published: February 2018

Aims and background

Lymph node metastases are rare in patients with follicular thyroid carcinoma, with an average incidence of 5.5% of all cases reported in the literature. In the present study we focused on the search for risk factors predictive of lymph node involvement in patients with follicular thyroid carcinoma to plan the most appropriate management and follow-up.

Methods and study design

We carried out a cross-sectional study among patients with follicular thyroid carcinoma and lymph node metastasis at diagnosis and patients without lymph node involvement. From January 1998 to April 2008, 930 patients underwent thyroidectomy in our surgical department for a variety of thyroid disorders, 420 (45.2%) of them for a differentiated thyroid carcinoma. The medical records of 55 patients with histological diagnosis of follicular thyroid carcinoma were analyzed.

Results

Four patients (7.3%) had lymph node metastasis from follicular thyroid carcinoma at presentation in both the lateral and central neck compartments. Mean tumor size was significantly greater for follicular thyroid carcinomas with nodal metastasis (5.1 ± 1.4 cm) than for those without nodal involvement (3.0 ± 1.2 cm, P <0.010). Among factors supposed to influence the presence of nodal metastasis at diagnosis (age, gender, tumor size, multifocality, tumor poorly differentiated, tumor widely invasive, vascular invasion, thyroid capsular invasion, and extra thyroid invasion), tumor size larger than 4.0 cm was the only factor retained in the multivariate statistical model.

Conclusions

Lymph node dissection must be planned only in the case of large follicular thyroid carcinomas. Since follicular carcinoma is usually diagnosed postoperatively, more attention should be paid to nodal involvement in the tumor re-staging during follow-up of those patients with tumors larger than 4.0 cm in diameter.
A possible mechanism of impaired NK cytotoxicity in cancer patients: Down-regulation of DAP10 by TGF-β1
Authors: Lee June-Chul , Lee Kyung-Mi , Ahn Yong-Oon , Suh Beomseok , Heo Dae Seog
Published: February 2018

Aims and background

Elevated TGF-β1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. However, the molecular mechanism of immunosuppression by TGF-β1 is not yet clarified.

Methods

IL-2-activated human NK cells were cultured with TGF-β1. Protein levels of NKG2D and DAP10 were examined by FACS or immunoblot analyses. Real-time RT-PCR was performed to quantify the transcription levels. MAPK inhibitors were used to investigate intracellular signaling.

Results

TGF-β1 down-regulated total and surface NKG2D, which was partially dependent on transcriptional regulation. TGF-β1 treatment of human NK cells resulted in significant changes in both transcriptional and translational levels of DAP10. Moreover, treatment with bafilomycin A1 or folimycin restored total NKG2D levels in TGF-β1-treated NK cells. The impaired NKG2D down-modulation by TGF-β1 was not associated with activation of the MAPK signaling pathway.

Conclusions

TGF-β1 down-modulates surface NKG2D expression by controlling the transcriptional and translational levels of DAP10.
Recurrent hepatocellular carcinoma in liver transplant recipients: Parameters affecting time to recurrence, treatment options and survival in the sorafenib era
Authors: Pfiffer Tulio EF , Seehofer Daniel , Nicolaou Annett , Neuhaus Ruth , Riess Hanno , Trappe Ralf U
Published: February 2018

Background

A growing number of patients with hepatocellular carcinoma undergo liver transplantation, but there is little data on recurrence and its treatment in the posttransplant setting.

Methods

This article presents a retrospective analysis of adult hepatocellular carcinoma patients. The aim of the study was to characterize the clinical pattern of posttransplant hepatocellular carcinoma recurrence, treatment options in recurrence and overall survival after liver transplantation and after recurrence.

Results

A total of 139 patients with histological proven hepatocellular carcinoma was included in the study. The median follow-up after liver transplantation was 37.2 months. Twenty-four of 139 patients experienced a recurrence. In 72.7% of the cases, the hepatocellular carcinoma recurred outside the transplant. Median overall survival after recurrence was 23.1 months. A total of 68.2% of patients received a mean of 2.2 treatments for posttransplant hepatocellular carcinoma recurrence. While on treatment with sorafenib, the use of mTOR inhibitors and radiotherapy had no statistically significant effect on overall survival, complete surgical resection of metastatic lesions significantly improved overall survival. Non-resectable patients with isolated hepatic relapse also benefited from local control strategies.

Conclusions

Posttransplant hepatocellular carcinoma recurrence frequently is located outside the transplant, and despite the proven efficacy of sorafenib, complete surgical resection of metastatic lesions remains the hallmark of treatment.
Feasibility of helical tomotherapy for radical dose retreatment in pelvic area: A report of 4 cases
Authors: Ricchetti Francesco , Barra Salvina , Agostinelli Stefano , Vagge Stefano , Marcenaro Michela , Corvò Renzo
Published: February 2018

Aims and background

To retrospectively determine acute toxicity and local control in patients with recurrence after definitive radiotherapy for prostate, bladder and rectal carcinoma.

Methods

Between September 2009 and March 2010, 4 patients with a prior history of pelvic radiotherapy were treated with helical tomotherapy. The prior course of radiotherapy was given for prostate cancer in 2 patients, bladder carcinoma in 1 patient and rectal carcinoma in 1 patient. The median prescribed dose of the prior course of radiotherapy was 6320 cGy (range, 5000–7600), and the median elapsed time between the first and second course was 17 months (range, 4–73). The total prescribed dose for tomotherapy retreatment was 60 Gy in 3 patients and 50 Gy in 1 patient. Hormone therapy was administered to 2 patients before and during radiation. No patient underwent surgical resection.

Results

The cumulative mean dose to the rectum ranged from 3813 to 6058 cGy; cumulative rectal maximum dose to 1 cc ranged from 6475 to 8780 cGy. Regarding the bladder, the cumulative mean dose was between 4384 and 7612 cGy; cumulative maximum dose to 1 cc ranged from 7560 to 9790 cGy. All patients completed the re-irradiation course. Acute genitourinary toxicity (RTOG scale) was grade 0 in 3 patients and grade 1 in 1 patient; acute gastrointestinal toxicity was grade 0 in 3 patients and grade 1 in 1 patient. With a median follow-up of 9 months (range, 7–12), late toxicity was G0 in all patients. Three patients showed partial response with computed tomography or magnetic resonance imaging, and 1 had a PSA decrease.

Conclusions

Re-irradiation with helical tomotherapy was well tolerated, with low rates of acute and late toxicity. It can be therefore considered a useful tool to improve local control in patients previously treated with radiotherapy. However, a larger number of patients and a longer follow-up are required to assess retreatment safety.
Geometry of volumes in radiotherapy planning. A new method for a quantitative assessment
Authors: Tomatis Stefano , Carrara Mauro , Massafra Elisa , Naldi Giovanni , Palazzi Mauro , Orlandi Ester , Marchesini Renato
Published: February 2018

Aims and background

The purpose of the study was to develop a general method able to quantify the mutual disposition in the 3D space of critical organs with respect to the target when these structures are designed for a radiotherapy treatment plan. To that end, we introduce the “expansion intersection histogram”, a function defined as the intersection between an organ at risk and the target volume, while the target is expanded in 3D.

Methods and study design

A software was developed to calculate the expansion intersection histogram of anatomical structures exported in a DICOM format from a commercial treatment planning system. A virtual phantom with spherical and cylindrical objects arranged in different dispositions in the 3D space was created for testing the software under known conditions.

Results and conclusions

Expansion intersection histogram computation was tested against reference data derived analytically for spherical volumes, with a resulting maximum error of 0.5%. Specific geometric features derived from the expansion intersection histogram, such as the distance between a selected target and each different ideal volume included in the virtual phantom, well matched the corresponding theoretical expected values. The expansion intersection histogram was evaluated also for the anatomical structures of a real patient. Data show this method as a tool to effectively take into account the mutual disposition of each critical organ with respect to the target, summarized in characteristics of distance, shape and orientation. The expansion intersection histogram method integrates and extends other preexisting modalities for evaluating the geometrical relationships among radiotherapy volumes and could be used to improve planning optimization.
Variation in gynecological oncology follow-up practice: Attributable to cancer centers or to patient characteristics? A Piedmont Regional Oncology Network Study
Authors: Fuso Luca , Evangelista Andrea , Pagano Eva , Piovano Elisa , Perotto Stefania , Mazzola Simona , Bertoldo Emiliana , La Porta Maria Rosa , Rosmino Claudia , Furbatto Graziella , Abate Sergio , Di Costanzo Gianna , Trossarelli Gianfranco , Baù Maria Grazia , Carnino Flavio , Gambaro Giuseppina , Piantanida Paola , Alabiso Oscar , Galletto Luciano , Zavallone Laura , Rossi Annalisa , Barbero Maggiorino , Tessa Maria , Katsaros Dionyssios , Danese Saverio , Brignolo Paola , Gorzegno Gabriella , Grillo Raffaella , Apolone Giovanni , Ciccone Giovannino , Zola Paolo
Published: February 2018

Aims and background

Although guidelines recommend minimalist follow-up, there is wide variability in gynecological oncology practice. The aims of this study were to describe between-center differences in the follow-up of endometrial, ovarian, and uterine cervical cancer; to identify the determinants of test prescription; to estimate the related costs; and to assess the weight of center habits and patient characteristics as sources of unexplained variability.

Methods and study design

The medical records of patients treated between August 2004 and July 2005 for gynecological malignancies and followed up for the detection of recurrent disease were retrospectively collected from 29 centers of the Piedmont Oncology Network. Multivariate multilevel analyses were performed to study the determinants of test prescription and costs.

Results

Analyses were performed on 351 patients (median follow-up: 578 days). The unexplained variability in computed tomography prescriptions (26%), ultrasound prescriptions (17%), and total cost of follow-up (15%) can be attributed to center habits, independenty of the clinical characteristics of the patients.

Conclusions

Much of the unexplained variability in the follow-up for gynecological malignancies is attributable to different habits of centers belonging to a cancer network. These results prompted us to design a multicenter randomized controlled trial to compare minimalist versus intensive follow-up programs in endometrial cancer.