ABSTRACT
OBJECTIVE: The aim of this study was to identify features mainly involved in determining the partial response (PR) to the Electrochemotherapy (ECT) in patients with recurrent and/or metastatic head and neck (H&N) tumor; the identified features were also used in a decision chart in order to provide the clinician with a support tool in deciding further therapies. PATIENTS AND METHODS: 131 patients (186 treatment sessions) with recurrent and/or metastatic H&N neoplasm were subjected to ECT. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 two months after the ECT. The grade of bleeding and pain before, at the end and one week after ECT treatment were evaluated. Univariate and multivariate analysis were performed to identify features involved in determining the patient PR. RESULTS: In the context of the univariate analysis, tumor size significantly influenced the response to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centimeters (p-value < 0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value < 0.001 at Chi-square test). A difference in the current flowing in the tissue during treatment was also observed in partially responsive patients, where the median current value (6.6 A) was higher than that achieved in patients that did not show PR (3.3 A). In the context of the multivariate analysis, the best performances are achieved with the BART method (accuracy of 84%). The main clinical factors to predict the partial response, among investigated features, that have shown to be considered were the pain value felt before performing the treatment and the median current delivered during the ECT treatment. A decision-making support tool to predict the patient prognosis in terms of response rate could be represented by the decision tree obtained with CART algorithm, where a pain pre-treatment more than 5 and a median delivered current not less than 2.8 A led to the prediction a partial responsive patient with an accuracy of 75%. CONCLUSIONS: The study confirmed that ECT is an interesting antitumoral therapy in advanced chemo- and radio-refractory H&N neoplasms, able to reduce frequent symptoms and to improve the quality of life. Pain pre-treatment and delivered current are the most important variables when predicting the partial response of patients.
Subject(s)
Electrochemotherapy , Head and Neck Neoplasms , Skin Neoplasms , Bleomycin/adverse effects , Electrochemotherapy/adverse effects , Head and Neck Neoplasms/drug therapy , Humans , Pain/drug therapy , Palliative Care/methods , Quality of Life , Skin Neoplasms/drug therapy , Treatment OutcomeABSTRACT
Nasopharyngeal carcinoma is a rare disease in Western countries. Nevertheless, its incidence in China, Singapore, and other Eastern countries reaches 20 cases per 100,000 people. Being an extremely chemo- and radiosensitive disease, upfront treatment often consists in the association of intensity-modulated radiation therapy and concurrent cisplatin. Unfortunately, about 20% of the patients suffer from a radioresistant disease which recurs after upfront therapy. For these patients, mainly available therapeutic options consist in systemic therapy, in particular poly-chemotherapy. In those showing a single locoregional recurrence, chemotherapy is not considered to be the preferred approach and other different strategies may be employed. Re-irradiation and surgery are strategies that are always used more often, albeit related to high risk of morbidity. Immunotherapy and targeted therapy, such as heavy ions-based re-irradiations, are experimental but very intriguing options.
ABSTRACT
BACKGROUND: Squamous Cell Carcinoma of the Head and Neck (SCCHN) are neoplasms arising from the epithelium of the first aero-digestive tract. They are very heterogeneous both clinically and biologically. Classic and well acknowledged risk factors are alcohol and tobacco consumption and other forms of smokeless tobacco assumption, although lately the incidence of Human Papilloma Virus (HPV)-related SCCHN is rapidly increasing. HPV-related tumors are very different from their alcohol and tobacco-associated counterpart, as they show strong chemo and radio sensitivity and thus can often be treated with conservative treatment strategies. Moreover, peculiar biologic features characterize HPV-related tumors, such as wild type TP53, low expression of Epidermal Growth Factor Receptor (EGFR), wild type CCND1 and high expression of P16. In contrast, alcohol and tobacco related SCCHN show opposite features, together with higher number of chromosomal and genetic abnormalities, conferring them chemo and radio resistance. METHODS: We have performed a narrative review of the PubMed database with the aim to study the mutational landscape of SCCHN. RESULTS: Several lines of evidence support the existence of at least two genetically different types of SCCHN, one virus-related and the other alcohol and/or tobacco-related, characterized by both clinical and biological opposite features. Virus related SCCHN are very chemo and radiosensitive, so suitable for organ preserving strategy, which in the near future may be induction chemotherapy followed by association of chemotherapy and underpowered radiotherapy. Alcohol and tobacco related SCCHN are themselves strongly heterogeneous and can be divided in different entities on the basis of the "Driver" genetic aberration, responsible for carcinogenesis. The most frequently mutated genes in alcohol and tobacco-related SCCHN are TP53, NOTCH1, CCND1, CDKN2A, EGFR and PI3KCA. CONCLUSIONS: Virus-related SCCHN can be managed with chemo-radiotherapy. Alcohol and tobacco-related tumors should be further characterized on the basis of their "Driver Mutations" in order to select effective targeted therapies.
Subject(s)
Head and Neck Neoplasms/etiology , Head and Neck Neoplasms/therapy , Squamous Cell Carcinoma of Head and Neck/etiology , Squamous Cell Carcinoma of Head and Neck/therapy , Alcohol Drinking/adverse effects , Animals , Disease Management , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/virology , Humans , Mutation , Papillomaviridae/isolation & purification , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/virology , Tobacco Smoking/adverse effects , Translational Research, BiomedicalABSTRACT
Tumours arising from the parapharyngeal space (PPS) represent less than 1% of all head and neck tumours. Salivary gland tumours account for 40-50% of PPS lesions and are located in the pre-styloid parapharyngeal space. Pleomorphic adenomas represent 80-90% of salivary tumours in the PPS. Recently, transoral robotic surgery (TORS) has become common in head and neck surgery as a minimally invasive procedure. Four cases of benign PPS tumour treated with TORS are presented here. Preoperative diagnosis was conducted by fine needle aspiration biopsy and magnetic resonance imaging, and the results were used to plan the correct surgical approach. One case required a change of approach to conventional transoral blunt dissection. Patients required pain control and reported dysphagia symptoms for a period of weeks, but no nasogastric tube was needed at any time. This case series indicates that TORS is a safe surgical procedure for the excision of benign tumours of the PPS in selected cases.
Subject(s)
Pharyngeal Neoplasms/surgery , Robotic Surgical Procedures/methods , Salivary Gland Neoplasms/surgery , Adult , Biopsy, Fine-Needle , Female , Humans , Length of Stay/statistics & numerical data , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local , Operative Time , Pharyngeal Neoplasms/pathology , Postoperative Complications , Salivary Gland Neoplasms/pathologyABSTRACT
Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. Gene expression is regulated at various levels and not only in response to DNA modifications. Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. Methylation of several tumor suppressor gene promoters is responsible for their silencing and thus potentially sustain cancerogenesis. Similarly, histone deacetylation can lead to oncogene activation. mi-RNA are small (18-20 nucleotides) non-coding RNA fragments capable of inhibiting other m-RNA, ultimately altering the balance in oncogene and tumor suppressor gene expression. It has been shown that growth of several tumor types can be stimulated by epigenetic changes in various phases of cancerogenesis, and drugs able to interfere with these mechanisms can have a positive impact on tumor progression. As matter of fact, epigenetic changes are dynamic and can be reversed by epigenetic inhibitors. Recently, methyltransferase and histone deacetylase inhibitors have attracted the attention of researchers and clinicians as they potentially provide alternative therapeutic options in some cancers. Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth. Epigenetic inhibitors work alone or in combination with other therapeutic agents. To date, a number of epigenetic inhibitors have been approved for cancer treatment. The main challenge in the field of epigenetic inhibitors is their lack of specificity. In this review article we describe their mechanisms of action and potential in cancer treatment.
Subject(s)
Neoplasms/drug therapy , Neoplasms/genetics , Carcinogenesis/genetics , DNA Methylation , Epigenesis, Genetic , Gene Expression , Histone Deacetylase Inhibitors/therapeutic use , Humans , Promoter Regions, GeneticABSTRACT
Bisphosphonates (BPs) are a class of synthetic drugs commonly used to treat bone metastasis and various bone diseases that cause osseous fragility (such as osteoporosis). Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common complication in patients who received BPs, especially intravenously. Recently, osteonecrosis of the jaw (ONJ) caused by chemotherapeutic not belonging to BPs drug class has been reported. For this reason, it has been proposed recently to rename BRONJ in antiresorptive agents related osteonecrosis of the jaw (ARONJ), to include a wider spectrum of drugs that may cause osteonecrosis of the jaw. The most debated topic about ARONJ/BRONJ is therapy. The most adequate procedure is far from being standardized and prevention seems to play a pivotal role. In our study, we considered 72 patients with BRONJ with nonsurgical therapy, surgical therapy, and surgical therapy with platelet rich plasma (PRP) gel to evaluate its therapeutic effect in promoting ONJ wounds healing. Good results showed by PRP in improving wound healing give away to case-control randomized studies that could give definitive evidence of its effectiveness.
ABSTRACT
BACKGROUND: The prognosis of the oral squamous cell carcinoma (OSCC) patients remains very poor, mainly due to their high propensity to invade and metastasize. E-cadherin reduced expression occurs in the primary step of oral tumour progression and gene methylation is a mode by which the expression of this protein is regulated in cancers. In this perspective, we investigated E-cadherin gene (CDH1) promoter methylation status in OSCC and its correlation with Ecadherin protein expression, clinicopathological characteristics and patient outcome. METHODS: Histologically proven OSCC and paired normal mucosa were analyzed for CDH1 promoter methylation status and E-cadherin protein expression by methylation-specific polymerase chain reaction and immunohistochemistry. Colocalization of E-cadherin with epidermal growth factor (EGF) receptor (EGFR) was evidenced by confocal microscopy and by immunoprecipitation analyses. RESULTS: This study indicated E-cadherin protein down-regulation in OSCC associated with protein delocalization from membrane to cytoplasm. Low E-cadherin expression correlated to aggressive, poorly differentiated, high grade carcinomas and low patient survival. Moreover, protein down-regulation appeared to be due to E-cadherin mRNA downregulation and CDH1 promoter hypermethylation. In an in vitro model of OSCC the treatment with EGF caused internalization and co-localization of E-cadherin with EGFR and the addition of demethylating agents increased E-cadherin expression. CONCLUSION: Low E-Cadherin expression is a negative prognostic factor of OSCC and is likely due to the hypermethylation of CDH1 promoter. The delocalization of E-cadherin from membrane to cytoplasm could be also due to the increased expression of EGFR in OSCC and the consequent increase of E-cadherin co-internalization with EGFR.
Subject(s)
Biomarkers, Tumor/genetics , Cadherins/genetics , Carcinoma, Squamous Cell/genetics , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , Mouth Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Antigens, CD , Antimetabolites, Antineoplastic/pharmacology , Biomarkers, Tumor/metabolism , Cadherins/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Cell Line, Tumor , DNA Methylation/drug effects , DNA Modification Methylases/antagonists & inhibitors , DNA Modification Methylases/metabolism , Down-Regulation , Enzyme Inhibitors/pharmacology , Epigenesis, Genetic/drug effects , ErbB Receptors/metabolism , Female , Gene Expression Regulation, Neoplastic/drug effects , Genetic Predisposition to Disease , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Mouth Neoplasms/metabolism , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Prognosis , Promoter Regions, Genetic , Protein Transport , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Squamous Cell Carcinoma of Head and Neck , Time FactorsABSTRACT
Status of lymph nodes of level IIb was examined to identify the incidence of nodal metastasis and the lymphatic drainage in squamous cell carcinoma of the oral tongue in patients undergoing modified radical neck dissection (MRND) and sentinel node biopsy (SNB). Overall, 72 patients were divided into two groups; 38 patients (Group A) of any T and N+ or T3-T4- N0 stage underwent MRND. The surgical specimens were sent to the Pathology Department, divided into specific levels (I, IIa, IIb, III, IV, V) and labelled. The remaining 34 patients (Group B) T1-T2 -N0 stage were submitted to SNB. The histological examination of the specimens of the two groups was performed by staining with haematoxylin and eosin several sections from each node at different levels and then using a molecular marker such as cytokeratin and Epithelial Membrane Antigen (EMA). In Group A: In N0 there were no occult metastases at level IIb; in N+ neck, 8 cases (33.3%) showed metastasis at level IIb (P = 0.04). Metastases at level IIb were observed only in combination with other levels (P = 0.03). In Group B, direct lymphatic drainage was found in 2 patients (5.9%) at level IIb. There were no occult metastases at level IIb. Out of the 54 sentinel nodes harvested, 4 lymph nodes (7.4%) were found to be metastatic; these 4 sentinel nodes were found respectively in 4 patients, 1 at level III, 3 at level II a with an occult metastasis rate of 11.7%. In conclusion, SNB has prospected a new concept of lymphatic drainage that is variable and individual. SNB has demonstrated that direct lymphatic drainage is possible to level II b. In our experience with early cancer of the tongue (T1-T2 NO ), SNB aided with lympho-scintigraphy seems to be a good technique for staging the neck with minimal morbidity.
Subject(s)
Carcinoma, Squamous Cell/secondary , Neck Dissection , Sentinel Lymph Node Biopsy , Tongue Neoplasms/pathology , Tongue Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/surgery , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neck , Neck Dissection/methods , Prospective Studies , Retrospective StudiesABSTRACT
OBJECTIVE: The purpose of the study was to assess whether partial cordectomy or complete cordectomy with narrow free margins is a safe oncological procedure for T1 glottic carcinoma. We also studied surgical margins and the involvement of anterior commissure. METHODS: Thirty-one T1 glottic carcinomas underwent endoscopic CO(2) laser excision of the lesion based on the depth of infiltration by the tumor with 1-2mm free margins. If detecting free margins was not macroscopically possible, additional biopsies along all the uncertain margins of the excision's residual area were taken. After excision, the specimen was mounted on a plastic support, flattened and then held in place with fine needles. It was then oriented and mapped. The pathologist measured the lesion's point of maximum infiltration and its distance from the free margins. RESULTS: Local and ultimate control at 36 months was 95% and 100%, respectively. We performed 29 partial and two complete cordectomies. Complete resection of the lesion was obtained in 90.4% of the cases. Re-resection was necessary in 9.6% of the cases due to positive margins. The anterior commissure was affected in 38.7% of the cases, and was the site of maximum infiltration in 9.6% of the cases. The mean maximum infiltration was 0.93mm in the anterior commissure, 2.18mm in the anterior 1/3rd of the vocal cord, 1.71mm in the middle 1/3rd of the vocal cord and 1.5mm in the posterior 1/3rd of the vocal cord. In 83.9% of the cases (p<0.01), the anterior 1/3rd of the vocal cord was the section most frequently involved. In 19 patients (61.3%) (p<0.01), the anterior 1/3rd of the vocal cord was also the area with the highest incidence of maximum infiltration by the tumor. CONCLUSION: We concluded that.
Subject(s)
Laryngeal Neoplasms/surgery , Laser Therapy/methods , Microsurgery/methods , Vocal Cords/surgery , Adult , Aged , Biopsy , Female , Humans , Laryngeal Neoplasms/pathology , Laryngoscopy/methods , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Reoperation , Sound Spectrography , Vocal Cords/pathology , Voice Disorders/diagnosis , Voice Disorders/etiologyABSTRACT
Squamous cell carcinoma of the oral cavity represents about 2% of all malignant neoplasms and 47% of those developing in the head and neck area. The tongue is the most common site involved, and this incidence is increasing mainly in young people, possibly related to human papilloma virus infections. Prognosis depends on the stage: the 5-year survival rate of tongue squamous cell carcinoma, whatever the T stage, is 73% in pN0 cases, 40% in patients with positive nodes without extracapsular spread (pNl ECS-), and 29% when nodes are metastatic with extracapsular spread (pNl ECS+: p > or = 0.0001). Nodal micrometastases (cN0 pN1) are found in up to 50% of cN0 tongue squamous cell carcinoma patients operated on the neck. At present, no clinical, imaging staging modalities or biological markers are available to diagnose nodal micrometastases. The sentinel node biopsy has been tested since 1996 in order to find a solution to this problem. The sentinel node is the first node reached by the lymphatic stream, assuming an orderly and sequential drainage from the tumour site, and should be predictive of the nodal stage. According to the literature, sentinel node biopsy is a reliable technique in selected cN0 cases, but the procedure is still experimental and should not be performed outside validation trials. Successful application of sentinel node biopsy in the head and neck region requires surgical experience and specific technical devices, including pre-operative lymphoscintigraphy and intra-operative gamma-probe. Moreover, dynamic lymphoscintigraphy seems to be able to show the lymphatic stream from the primary tumour and could allow a selective neck dissection to be tailored thus reducing the related morbidity.
Subject(s)
Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/pathology , Sentinel Lymph Node Biopsy , Carcinoma, Squamous Cell/surgery , Humans , Mouth Neoplasms/surgery , Neck DissectionABSTRACT
Squamous cell carcinoma (SCC), the most frequent malignant tumor of the oral cavity, generally exhibits a poor prognosis and metastases are the main cause of death. This tumor often arises from pre-malignant lesions. To date, it is difficult to predict if and which pre-malignant lesions may progress into oral SCC using traditional methods. For these reasons, several studies are trying to identify markers useful in the progression of pre-malignant lesions and tumors. To define the genetic expression profile of tongue tumor progression we compared 9 dysplasias (DS), 8 tumors without metastasis (TWM), 11 metastasizing SCCs (MT) of the tongue, and a baseline of 11 normal tissues by using cDNA microarray containing 19.2 K clones. We initially applied hierarchical agglomerative clustering based on information from all 6026 clones. Results were obtained by performing a two steps analysis: a Significance Analysis of Microarray (SAM) and a Gene Ontology search. One hundred and five clones have statistically significant different expression levels (FDR < 0.01) between DS and TWM, whereas 570 genes have statistically significant difference expression levels between TWM and MT (FDR < 0.01) as detected by SAM. By filtering with FatiGo only 33 genes were differentially expressed in TWN, respect to DS, whereas 155 genes were differentially expressed in MT respect to TWM. We detected some genes which encode for oncogenes, transcription factors and cell cycle regulators as potential markers of DS progression. Examples are BAG4, PAX3 and CCNI, respectively. Among potential markers of metastases are some genes related to cell mobility (TSPAN-2 and SNTA1), intercellular adhesion (integrin alpha 7) or extracellular matrix components (ADAMTS2 and cathepsin O). Additionally, under-expressed genes encoded apoptosis-related proteins (PDCD4 and CASP4). In conclusion, we identified several genes differentially expressed in tumor progression which can potentially help in better classifying pre-malignant lesions and tongue SCCs.
Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Squamous Cell/genetics , Oligonucleotide Array Sequence Analysis , Tongue Neoplasms/genetics , Tongue/pathology , Adult , Aged , Aged, 80 and over , Algorithms , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , DNA, Complementary/genetics , DNA, Neoplasm/genetics , Disease Progression , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Precancerous Conditions/classification , Precancerous Conditions/genetics , Precancerous Conditions/metabolism , Software , Tongue Neoplasms/diagnosis , Tongue Neoplasms/metabolism , Tongue Neoplasms/surgeryABSTRACT
UNLABELLED: AIMS AND BACKGROUNDS: In T1-T2a glottic carcinoma before considering which type of treatment is the best option a biopsy is necessary. A peculiar aspect of this type of lesions is the fact that in the same specimen it is possible to find different grade of dysplasia even carcinoma in situ or microinvasive or invasive. An incisional biopsy could mislead the diagnosis. The aim of this study was to report the oncological results of the excisional biopsy for T1-T2a glottic cancer. MATERIALS AND METHODS: From November 1999 to December 2001, 18 patients (13 T1, 5 T2a) with carcinoma of the vocal cord underwent excisional biopsy of the lesion. In the case of negative margins no further treatment was done. The average follow-up was 2 years and 3 months. RESULTS: Local control was achieved in 100% for T1, 80% for T2. Radiotherapy was added in 2 cases. CONCLUSION: In our experience "excisional biopsy" for unadvanced glottic tumors is an ideal surgical technique for a one stage procedure of diagnosis and therapy.
Subject(s)
Biopsy/methods , Carcinoma/pathology , Endoscopy , Glottis/pathology , Laryngeal Neoplasms/pathology , Carcinoma/diagnosis , Carcinoma/radiotherapy , Carcinoma/surgery , Combined Modality Therapy , Follow-Up Studies , Glottis/surgery , Humans , Laryngeal Neoplasms/diagnosis , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/surgery , Lasers , Neoplasm Recurrence, Local , Retrospective Studies , Treatment Outcome , Vocal Cords/surgeryABSTRACT
UNLABELLED: AIMS AND BACKGROUNDS: The use of the stapler in total laryngectomy with closed technique is described by the authors. MATERIALS AND METHODS: From October 1999 to December 2002, 27 total laryngectomy were performed, 15 with a stapler and 5 cases had a primary tracheoesophageal puncture. RESULTS: Only one patient developed a pharyngocutaneous fistula, no other patients experienced post-operative complications. All cases in this study had negative surgical margins. CONCLUSION: The correct indication for the use of the stapler is a tumor that needs a total laryngectomy, but completely endolaryngeal. The technique allows to remove the nso-gastric tube at the end of the first week after the operation, to avoid soiling the surgical field, to reduce the time in theatre. This technique seems to be safe as the traditional suture.
Subject(s)
Laryngectomy/methods , Surgical Stapling , Combined Modality Therapy , Cutaneous Fistula/etiology , Fistula/etiology , Humans , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/surgery , Laryngectomy/instrumentation , Pharyngeal Diseases/etiology , Postoperative Complications , Radiotherapy, Adjuvant , Retrospective StudiesABSTRACT
In the surgery of malignancies of the parotid gland the management of the facial nerve and of the neck is very important. In fact, many authors declared as the surgery of parotid gland can be considered as the surgery of facial nerve and others underlined the role of the neck management in a complete treatment of these neoplasms. The features of 47 cases of parotid gland neoplasms observed at the National Cancer Institut of Naples (Naples, Italy) are reported. In all cases a total parotidectomy was performed with neck dissection in case of neck metastases or electively in selected cases and resection of the facial nerve only in case of macroscopic tumor involvement. Radiotherapy was administrated in case of involvement of the facial nerve, and/or of the skin and/or of multiple neck metastases. The results of our experience emphasize as the neoplasms of the parotid gland can be treated sparing the facial nerve when it is clearly not involved without making worse prognosis; on the other side planing a neck dissection should be mandatory in case of high degree malignancies, and/or of tumors larger than T2, and/or of involvement of the facial nerve, and/or of the skin and/or cervical lymph nodes.
Subject(s)
Carcinoma/surgery , Facial Nerve/surgery , Neck Dissection/methods , Parotid Neoplasms/surgery , Adult , Carcinoma/radiotherapy , Combined Modality Therapy , Facial Nerve/pathology , Facial Nerve Injuries/prevention & control , Female , Humans , Intraoperative Complications/prevention & control , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Parotid Neoplasms/radiotherapy , Retrospective StudiesABSTRACT
AIMS AND BACKGROUND: In stage I oral squamous cell carcinoma, clinical examination and imaging techniques are unable to identify 60-90% of patients at risk of micrometastasis, while the sentinel node biopsy technique allows to avoid the morbidity of elective neck dissection in patients not actually affected by micrometastases. MATERIALS AND METHODS: Forty-one T1-T2N0 patients underwent lymphoscintigraphy after peritumoral injection of human albumin labeled with 99Tc. Focal areas of radiotracer uptake were marked on the skin preoperatively. The sentinel lymph node (SLN) was identified by the combined use of blue dye and gamma probe and subsequently removed. Complete neck dissection was then performed in all patients and the histological findings were compared with those of SLN biopsy. RESULTS: The SLN was identified in 95% of the patients; in four cases (10%) two SLNs were isolated. In 18% of our patients the SLNs were located outside the expected drainage area. When the histology of the negative SLNs was compared with the pathological status of the neck dissection specimens no false negatives were found. Five SLNs in four patients contained micrometastases and were the only positive lymph nodes. CONCLUSIONS: SLN biopsy can be a valuable staging technique in T2 and T2 oral cancer with uninvolved neck in patients whose lymphatic drainage of the neck has not been altered by previous surgery or radiotherapy. It provides reliable detection of micrometastasis, indicating which level(s) should be removed ipsilaterally or contralaterally, and allows the surgeon to accurately plan neck dissection, taking into consideration the pattern of lymphatic drainage of each individual patient. In this way unnecessary neck dissection and its morphofunctional sequelae can be avoided in a considerable number of patients.
Subject(s)
Carcinoma, Squamous Cell/pathology , Lymph Nodes/pathology , Mouth Neoplasms/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/surgery , Female , Humans , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Middle Aged , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/surgery , Neck Dissection/methods , Neoplasm Staging , Predictive Value of Tests , Prognosis , Radionuclide ImagingABSTRACT
The purpose of this study was to assess the value of sentinel node (SN) biopsy in oral cancer by means of a lymphoscintigraphic technique and intraoperative detection by blue-dye combined with gamma-ray probe to facilitate identification of the SN. Forty-one T1-T2N0 patients underwent lymphoscintigraphy, SN biopsy, and modified radical neck dissection. An SN was identified in 39 of 41 patients by the combined use of intraoperative blue dye and the probe and was removed. Complete neck dissections were performed and the histological evaluation compared. Thirty-eight SNs in 35 patients were negative at final pathology and correctly predicted the pathological status of the specimens from the full-neck dissections. Five SNs in four patients had micrometastases and were the only metastatic nodes identified. The results of this study on a homogenous series of patients show that SN biopsy is a valuable staging technique in T1 and T2 oral cancer with uninvolved neck, provided that no previous surgery or radiotherapy has altered lymphatic drainage in the oral cavity or in the neck. In a large number of patients, SN biopsy can avoid unnecessary neck dissection and its relevant morphofunctional sequelae.
Subject(s)
Carcinoma, Squamous Cell/secondary , Mouth Neoplasms/pathology , Sentinel Lymph Node Biopsy/methods , Coloring Agents , Head and Neck Neoplasms/pathology , Humans , Neoplasm Staging , Radiopharmaceuticals , Technetium Tc 99m Aggregated AlbuminSubject(s)
Community Health Services , Melanoma/diagnosis , Mobile Health Units , Skin Neoplasms/diagnosis , Adolescent , Adult , Aged , Child , Child, Preschool , Dermatology/methods , Female , Humans , Italy , Male , Microscopy , Middle AgedABSTRACT
PURPOSE: We have recently evaluated the combination of raltitrexed, levofolinic acid (LFA) and 5-fluorouracil (5-FU) in advanced head and neck and colorectal cancer, and we have shown that this combination is well tolerated and has clinical activity. Clinical combination studies have shown that raltitrexed and anthracyclines can be combined at full doses without unexpected toxicities. Based on these observations, we started a phase I study of mitoxantrone plus raltitrexed administered on day 1, followed by LFA and 5-FU on day 2 in patients with advanced solid tumors. PATIENTS AND METHODS: Mitoxantrone was given at a starting dose of 6 mg/m2, raltitrexed at a fixed dose of 3 mg/m2, LFA at a fixed dose of 250 mg/m2, and 5-FU at a starting dose of 750 mg/m2. Mitoxantrone and 5-FU doses were subsequently escalated alternately up to dose-limiting toxicity. Treatment was repeated every 14 days. RESULTS: Four dose levels were tested in 18 patients. All three patients treated at the fourth dose level had grade 4 neutropenia after the first cycle. Therefore, this level was defined as the maximum tolerated dose and the dose level immediately below (mitoxantrone 7 mg/m2 and 5-FU 900 mg/m2) was selected for further evaluation. Neutropenia was the main toxic effect. Nonhaematologic side effects were mild. One complete response and five partial responses (all but one in patients with head and neck cancer) were observed, for an overall response rate of 33% (95% confidence interval, 13% to 59%). CONCLUSIONS: Mitoxantrone, raltitrexed and 5-FU can be combined at doses which are close to those used in monotherapy. The observed activity is encouraging, especially in the subset of patients with head and neck cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/drug therapy , Female , Fluorouracil/administration & dosage , Head and Neck Neoplasms/drug therapy , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Mitoxantrone/administration & dosage , Quinazolines/administration & dosage , Thiophenes/administration & dosageABSTRACT
PATIENT: A case of Turner's syndrome developing a leiomyosarcoma of the oropharynx and metachronous neurogenic tumors (mediastinal 'ganglioneuroblastoma intermixed', subcutaneous neurilemoma) is described. DISCUSSION: To our knowledge, this case is the second reported leiomyosarcoma in a patient with Turner's syndrome. Also the site of involvement (palate and oropharynx) is particularly unusual for the already rare leiomyosarcomas in the young age.
ABSTRACT
BACKGROUND: The combination of cisplatin (CDDP) and 5-fluorouracil (5-FU) can be regarded as a reference regimen in squamous cell carcinoma of the head and neck (SCCHN). Raltitrexed (Tomudex) is a direct and specific thymidilate synthase (TS) inhibitor, which has shown clinical activity against SCCHN in a previous phase I study, when combined with 5-FU and levo-folinic acid (LFA). Preclinical data support the combination of CDDP and raltitrexed. The aim of the present study was to evaluate the combination of cisplatin, raltitrexed. LFA and 5-FU in a phase I-II study. PATIENTS AND METHODS: Patients with locally advanced or metastatic SCCHN were treated with a combination of cisplatin at the starting dose of 40 mg/m2. followed by raltitrexed at the starting dose of 2.5 mg/m2 on day 1; levo-folinic acid at fixed dose of 250 mg/m2, followed by 5-fluorouracil at the starting dose of 750 mg/m2 on day 2. Doses of the three cytotoxic agents were alternately escalated up to dose-limiting toxicity (DLT). Treatment was recycled every two weeks and given up to a maximum of eight courses; after chemotherapy, patients with locally advanced disease received a locoregional treatment. RESULTS: Forty-five patients were entered into the study. Six dose levels were tested. At CDDP 50 mg/m2, raltitrexed 3 mg/m2, 5-FU 900 mg/m2, four out of six patients showed DLT, which was in all cases grade 4 neutropenia. Therefore, this dose level was defined as maximum tolerated dose (MTD). CDDP 60 mg/m2, raltitrexed 2.5 mg/m2, LFA 250 mg/m2, 5-FU 900 mg/m2 was the dose level recommended for phase II. CDDP, Raltitrexed and 5-FU mean actually delivered dose intensities at the selected dose level were 26, 1.05, and 378 mg/m2/week, respectively. Neutropenia was the main side effect and was observed even at the lowest dose levels. Nonhematologic side effects were mild. Nine complete responses (20%) and twenty-one partial responses (47%) were observed, for an overall response rate of 67% (95% confidence interval (95% CI): 51%-80%), according to intention to treat analysis. Fifteen of fifteen patients (100%) treated at the dose level selected for phase II had an objective response (5 complete responses, 10 partial responses). CONCLUSIONS: The results of our dose escalation clearly demonstrate that it is possible to combine CDDP, raltitrexed, and modulated 5-FU at effective doses, without unexpected toxicities. The response data point to an impressive clinical activity, which will be better defined by an ongoing large phase II study.