Radical Resection of Malignant Tumors of Major Salivary Glands: Is This Possible?

In primary therapy, a universally recognized surgical indication applies to all tumors of the salivary glands. According to the classic rule, radical resection of a head and neck tumor requires clean margins of at least 5 mm, although recent studies have shown that for certain locations, 1 mm may be sufficient. In the surgical resection of a tumor of the salivary glands, especially of the parotid gland, can these rules be respected? Owing to the complex branching and connections of the facial nerve within the parotid gland, even a medium-sized malignant tumor may be in contact with a branch of the nerve, thus raising the question of its preservation. The facial nerve is so important from a functional and aesthetic point of view that it is commonly believed that it should be preserved unless it is incorporated into the tumor. This is a compromise between an oncological resection, that is, the complete excision of the tumor with no residual cancer cells left behind, and quality of life. Almost all authors try to overcome this lack of radicality by indicating postoperative (chemo)radiotherapy. In this article, the pros and cons of nerve preservation will be analyzed by examining the published studies on this topic.

Adenoid cystic carcinoma. An indolent but aggressive tumour. Part B: treatment and prognosis.

The purpose of this review is to analyse the very large number of studies (sometimes contradictory) on adenoid cystic carcinoma (ACC). This second part provides a critical analysis of various treatment described in the literature. Anywhere the primary tumour is located, the most common treatment for ACC is complete surgical resection, with or without post-operative radiotherapy (PORT), while conventional photon and/or electron radiotherapy alone and chemotherapy are commonly used in unresectable or metastatic disease. Fast neutron radiotherapy was used in the past with good local results, but the risk of late effects was high and tended to increase over time. Modern carbon-ion radiotherapy seems to be a valid option in selected cases. The quite universally accepted poor prognostic factors are advanced stage, perineural and intraneural invasion, involved margins, and initial presence or later development of neck metastases. The impact of histologic grade on prognosis is controversial. Owing to the long natural history of ACC, the follow-up for patients must be at least 10 years long.^ieng

Il proposito di questa review è quello di analizzare il grande numero di studi (talvolta contradittori) sul carcinoma adenoide cistico. Questa seconda parte presenta una analisi critica dei vari trattamenti descritti in letteratura. Ovunque il tumore primitivo sia localizzato il trattamento più indicato è una resezione radicale con o senza radioterapia postoperatoria. La radioterapia convenzionale con fotoni e/o elettroni e la chemioterapia sono comunemente riservate ai casi inoperabili o metastatici. La radioterapia con neutroni è stata ampiamente utilizzata in passato con buoni risultati locali, ma il rischio di effetti collaterali tardivi si è dimostrato alto e con tendenza ad aumentare nel tempo. Il moderno trattamento con ioni carbonio si sta dimostrando una valida alternativa in casi selezionati. I fattori prognostici negativi quasi universalmente accettati sono lo stadio avanzato, l'invasione perineurale e intraneurale, i margini positivi e le metastasi linfonodali alla presentazione o successive. Il valore prognostico del grading istologico è controverso. Stante la lunga storia naturale del carcinoma adenoide cistico il follow-up dei pazienti deve essere almeno di 10 anni.

Adenoid cystic carcinoma. An indolent but aggressive tumour. Part A: from aetiopathogenesis to diagnosis.

Adenoid cystic carcinoma (ACC) is a relatively rare tumour of the minor and major salivary glands. It is uncommon in the parotid gland while it is much more frequent in the submandibular gland and in minor salivary and mucinous glands (oral cavity, oropharynx, and paranasal sinuses). ACC may also arise in secretory glands located in other tissues, such as in the tracheobronchial tree, oesophagus, breast, lungs, prostate, uterine cervix, lachrymal and Bartholin's glands, and skin. The natural history of ACC is characterised by an indolent growth rate, a relatively low probability of regional lymph node metastases and a high likelihood of haematogenous dissemination. ACC has been traditionally subdivided into three histological groups (cribriform, tubular, and solid) based on solid components of the tumour. Some studies have shown that tumours with a solid growth component have a rapid fatal course, compared to tumours without a solid growth component, but other studies have failed to correlate growth patterns with clinical course. The purpose of this review is to analyse the very large number of studies (sometimes contradictory) on ACC. In this first part, the aetiology, epidemiology, histopathology, clinical behaviour and diagnostic workup are examined.^ieng

Il carcinoma adenoide cistico (ACC) è un tumore relativamente raro ad origine dalle ghiandole salivari minori e maggiori. È poco frequente nella parotide mentre lo è molto di più nella ghiandola sottomandibolare, nelle ghiandole salivari minori e in quelle mucinose del cavo orale, orofaringe e seni paranasali. Esso può anche insorgere nelle ghiandole secretrici localizzate in altri tessuti come l'albero tracheo-bronchiale, l'esofago, la mammella, il polmone, la prostata, la cervice uterina, la cute, le ghiandole lacrimali e quelle del Bartolini. La sua storia naturale è caratterizzata da una lenta crescita, da rare metastasi linfonodali e da frequenti metastasi a distanza. Dal punto di vista istologico esso è stato tradizionalmente suddiviso in tre forme (cribriforme, tubulare e solido). Alcuni studi hanno dimostrato che i tumori con una prevalente componente solida hanno una prognosi peggiore rispetto a quelli con prevalente componente cribriforme o tubulare ma altri studi hanno contestato questa affermazione. Il proposito di questa review è quello di analizzare il grande numero di pubblicazioni (talvolta contraddittorie) sul carcinoma adenoide cistico. In questa prima parte saranno discusse l'eziologia, l'epidemiologia, l'istopatologia, la presentazione clinica e l'iter diagnostico.

Tp53 status as guide for the management of ethmoid sinus intestinal-type adenocarcinoma.

OBJECTIVE: Intestinal-type adenocarcinoma (ITAC) of the ethmoid sinus is a rare, occupational-related tumor. Optimal treatment consists of surgery and radiotherapy, while chemotherapy is still investigational. The molecular profile of ITAC is characterized by the occurrence of TP53 mutations associated with genotoxic agents such as wood dust. We investigated the role of p53 functionality in relation to the primary treatment. MATERIALS AND METHODS: We retrospectively reviewed 100 medical charts of consecutive patients with a first diagnosis of ITAC treated at our Institute; 74 patients were evaluable for TP53 analysis. Thirty (41%) were treated from 1991 to 2006 with craniofacial resection followed by radiotherapy (Group A), compared with 44 patients (59%) treated from 1996 to 2006 with cisplatin-based induction chemotherapy (PFL) followed by standard treatment (Group B). RESULTS: Five-year OS in Group A was 42%, while in Group B it was 70% (p = 0.041); 5-year DFS in Group A was 40%, while in Group B it was 66%, (p = 0.009) (p = 0.061 and 0.003 at Cox multivariable OS and DFS analyses). Analyzing each group according to p53 functional status, only for Group B patients (who received preoperative chemotherapy) both OS and DFS were in favor of functional p53 (p = 0.023 and p = 0.010, respectively). No impact of p53 functional status as a biomarker was observed in Group A. CONCLUSIONS: Functional p53 may predict PFL-chemotherapy efficacy, offering a possible increase in survival when induction chemotherapy is given to a selected population. On the other hand, upcoming innovative approaches should be explored in the presence of non-functional p53.

Anterior craniofacial resection for malignant paranasal tumors: a monoinstitutional experience of 366 cases.

BACKGROUND: The purpose of this study was to evaluate the results of a mono-institutional series of patients treated with anterior craniofacial resection for malignant paranasal sinus tumors. METHODS: We analyzed all patients with malignant paranasal sinus tumors treated with anterior craniofacial resection at our institution between 1987 and 2007. All tumors were classified according to both the American Joint Committee on Cancer (AJCC)-2002 and the Istituto Nazionale Tumori (INT) classifications. RESULTS: The sample included 366 patients. There was intraorbital spread in 108 cases. The skull base was eroded in 127 patients, with dura or brain involvement in 93 patients. The 10-year disease-specific survival was 53.1%. Histologic subtype, INT stage, surgical margins, and postsurgical radiotherapy were significant, independent predictors for both local relapse and disease-specific survival (DSS). The AJCC-2002 classification was not significant when tested in place of INT stage. CONCLUSION: Our data indicated that craniofacial resection and postsurgical radiotherapy remain the primary option for malignant tumors involving the anterior skull base.

Craniofacial surgery for esthesioneuroblastoma: report of an international collaborative study.

Introduction Impact of treatment and prognostic indicators of outcome are relatively ill-defined in esthesioneuroblastomas (ENB) because of the rarity of these tumors. This study was undertaken to assess the impact of craniofacial resection (CFR) on outcome of ENB. Patients and Methods Data on 151 patients who underwent CFR for ENB were collected from 17 institutions that participated in an international collaborative study. Patient, tumor, treatment, and outcome data were collected by questionnaires and variables were analyzed for prognostic impact on overall, disease-specific and recurrence-free survival. The majority of tumors were staged Kadish stage C (116 or 77%). Overall, 90 patients (60%) had received treatment before CFR, radiation therapy in 51 (34%), and chemotherapy in 23 (15%). The margins of surgical resection were reported positive in 23 (15%) patients. Adjuvant postoperative radiation therapy was used in 51 (34%) and chemotherapy in 9 (6%) patients. Results Treatment-related complications were reported in 49 (32%) patients. With a median follow-up of 56 months, the 5-year overall, disease-specific, and recurrence-free survival rates were 78, 83, and 64%, respectively. Intracranial extension of the disease and positive surgical margins were independent predictors of worse overall, disease-specific, and recurrence-free survival on multivariate analysis. Conclusion This collaborative study of patients treated at various institutions across the world demonstrates the efficacy of CFR for ENB. Intracranial extension of disease and complete surgical excision were independent prognostic predictors of outcome.

Intestinal type adenocarcinoma of the ethmoid sinus in wood and leather workers: a retrospective study of 153 cases.

BACKGROUND: The purpose of our study was to identify the role of work exposure to organic dusts in patients with malignant paranasal sinus tumors. METHODS: We analyzed all patients surgically treated for a malignant paranasal sinus tumor at our institution between 1987 and 2006. All patients were specifically asked about their occupational history. The tumor site was classified as maxillary or ethmoid sinus. Adenocarcinomas were divided into intestinal type (ITAC) and non-ITAC. RESULTS: The sample included 345 patients with ethmoid sinus and 301 maxillary sinus. Regarding the ethmoid sinus, we found an exposure to organic dusts in 148 of 153 patients with ITAC, in 3 of 16 patients with non-ITAC adenocarcinoma, and in 10 of 176 patients with other tumors. Regarding the maxillary sinus, we found an exposure in 1 of 20 patients with non-ITAC adenocarcinoma and in 4 of 281 patients with other histologies. CONCLUSION: Our study demonstrates that only ethmoid ITACs have an indisputable relationship with the exposure to organic dusts.

Recent advances in managing human papillomavirus-positive oropharyngeal tumors.

Human papillomavirus (HPV) is detected in a subset of patients with head and neck squamous cell carcinoma, most frequently in tumors in the Waldeyer's ring (palatine tonsil and base of tongue). Several studies suggest that patients with HPV-positive tumors have better survival with either concurrent chemoradiation therapy or surgery followed by radiation compared with HPV-negative patients. However, some possible confounding clinicopathologic variables may challenge the validity of this statement, for example, some authors used the TNM (tumor, node, metastasis) grouping stage while others used the primary tumor (T stage), and other studies have demonstrated that tumors with advanced T stage were less likely to be infected with HPV. A large clinical trial with stratification of patients according to all known tumor prognostic factors is crucial to solve the question.

Surgery for malignant maxillary tumors involving the middle cranial fossa.

The purpose of this study was to evaluate the disease-free survival (DFS) of patients with maxillary malignant tumors invading the middle cranial fossa (MCF) who underwent a lateral or anterolateral skull base resection. This study was a retrospective analysis in a tertiary referral center and included 62 patients with maxillary malignant tumors invading the MCF (stage T4b) treated with surgery with or without postoperative radiotherapy. All patients had sharp pain and involvement of at least one branch of the trigeminal nerve. Twenty-eight patients had not been treated previously, and 34 had previously been treated elsewhere. The MCF dura was infiltrated and resected in 36 cases, and in nine of these, there was an intradural extension of the tumor, with temporal lobe and/or cavernous sinus invasion. Thirty-six patients underwent reconstruction with a temporalis muscle pedicled flap, and 26 patients with a free flap. There was a 22% overall rate of postoperative complications, but no intraoperative deaths. The median follow-up time was 49 months (range 2 to 186). Overall DFS was 33.9% and was higher for untreated patients (46.4% versus 23.5%) and for patients in whom clean margins were achieved (51.4% versus 12.5%). The survival time for patients who died of disease was 9 months for squamous cell carcinoma and 38 months for adenoid-cystic carcinoma. All patients experienced anesthesia in the territory of the resected trigeminal branches, but their pain vanished, and their quality of life improved. Lateral skull base surgery may achieve satisfactory oncologic results for patients with low-grade tumors, with improved quality of life for almost all patients.

Autologous freeze-treated bone for mandibular reconstruction after malignant tumor resection: a study of 72 patients.

OBJECTIVE: The aim of the study was to assess the possibility of mandibular reconstruction with autologous freeze-treated bone after mandibular resection for malignant tumors. PATIENTS: The medical records of 72 consecutive patients surgically treated with segmental mandibular resection and reconstruction with autologous freeze-treated mandible were reviewed. RESULTS: All tumors were in stage T4a for deep infiltration of the mandible. Soft tissues were reconstructed with a direct mucosal closure (4 cases), with a pedicled pectoralis flap (17 cases), and with a forearm fasciocutaneous free flap without or with radial periosteum (18 and 33 cases). Four patients presented with a recurrence after previous surgery and radiotherapy, and 26 patients underwent postoperative radiotherapy. We resected the mental arch in 35 cases and the lateral mandible in 37 cases. Forty-one patients (56.9%) retained their autologous mandibular graft. In 31 cases, the bone graft was removed for mucosal dehiscence and bone infection. Lateral resections achieved a better success rate than anterior resections (75.7% vs 37.1%). The pedicled pectoralis flap achieved the worse success rate (35.3%) in comparison with forearm fasciocutaneous flap (66.7%). Postoperative radiotherapy decreased the success rate (40.0% vs 69.1%). CONCLUSIONS: Mandibular reconstruction with autologous frozen bone is an interesting alternative to more sophisticated methods for patients with oral cancer involving the bone. It is time and cost sparing in comparison to fibula or iliac crest flaps. However, in spite of any intraoral reconstruction, the success rate is not stirring. In our opinion, this type of mandibular reconstruction must be reserved to patients with lateral tumors, with poor prognosis, or severe comorbidities not allowing more complex bone reconstruction.

Polymorphisms of Metabolizing Enzymes and Susceptibility to Ethmoid Intestinal-type Adenocarcinoma in Professionally Exposed Patients.

Intestinal-type adenocarcinoma (ITAC) of ethmoid is a rare tumor associated with occupational exposure to wood and leather dusts. Polymorphisms in xenobiotic metabolizing enzymes play an important role in gene-environment interactions and may contribute to a high degree of variance in individual susceptibility to cancer risk. The aim of this study was to investigate by polymerase chain reaction the role of polymorphisms at CYP1A1 and GSTM1 genes in 30 ethmoid ITAC patients and 79 healthy donors. The distribution of Thr/Asn genotype at CYP1A1 codon 461 was significantly overrepresented among the patients (23.3%; P = .0422), whereas the Ile/Val genotype at CYP1A1 codon 462 was not significantly different between cases and controls (P = .76). The GSTM1 null genotype was not significantly different between cases and control (P = 1), but we observed that the combined codon 461 Thr/Asn and GSTM1 null genotype was overrepresented in the patient group (P = .0019). The results reveal that patients with CYP1A1 codon 461 polymorphism may be at high genetic risk of ITAC and that the risk increases in the presence of combined polymorphism of CYP1A1 and GSTM1 null genotype. This strongly suggests that CYP1A1 codon 461 and GSTM1 null genotype may be useful in selecting exposed individuals at risk for ethmoid ITAC.

Survival for ethmoid sinus adenocarcinoma in European populations.

BACKGROUND: Adenocarcinoma of the ethmoid sinus is rare. EUROCARE data provide a good opportunity to study the survival of this rare disease in a population of continental size. PATIENTS AND METHODS: A total of 204 cases, age 15 to 99 years, diagnosed with primary ethmoid sinus adenocarcinoma between 1983 and 1994, were analyzed. The data were contributed by 22 population-based cancer registries from the nine countries participating in EUROCARE. Relative survival by sex, age, period of diagnosis, region and stage, and adjusted relative excess risk (RER) of death, were estimated. RESULTS: Survival was 83%, 58% and 46%, 1, 3 and 5 years, respectively after diagnosis. Five-year survival was best (60%) in patients of 55-64 years and worst (33%) in the oldest age group (> or =65 years). Five-year survival differ between European population: in Norway (55%, 95% confidence interval 26.4-80.9) and western Europe that includes populations from Eindhoven, Saarland, Geneva, Italy and France (56%, 95%CI 41.3-68.9) was higher than in the UK (41%, 95% CI 30.8-51.8) and eastern Europe which includes Slovakia and Slovenia, (22%, 95% CI 3.5-54.4). Five-year survival did not improve over time. Due to the rarity of the disease, all the survival differences did not reach the statistical significance. CONCLUSIONS: Since no survival improvement with time was evident from this study, efforts should be made to improve early diagnosis. GPs and ENT specialists should be alerted to the disease and encouraged to take occupational histories in people with persistent nasal symptoms, which may lead to a reasonable suspicion of malignancy. Monitoring of exposed workers may also improve early diagnosis. Patients with suspected ethmoid cancer should be referred immediately a specialized diagnosis and treatment centre.

Further improvement in outcomes of nasopharyngeal carcinoma with optimized radiotherapy and induction plus concomitant chemotherapy: an update of the Milan experience.

PURPOSE: To report the outcome of a consecutive series of patients with nonmetastatic nasopharyngeal carcinoma (NPC), focusing on the impact of treatment-related factors. METHODS AND MATERIALS: Between 2000 and 2006, 87 patients with NPC were treated with either conventional (two- or three-dimensional) radiotherapy (RT) or with intensity-modulated RT (IMRT). Of these patients, 81 (93%) received either concomitant CHT (24%) or both induction and concomitant chemotherapy (CHT) (69%). Stage was III in 36% and IV in 39% of patients. Outcomes in this study population were compared with those in the previous series of 171 patients treated during 1990 to 1999. RESULTS: With a median follow-up of 46 months, actuarial rates at 3 years were the following: local control, 96%; local-regional control, 93%; distant control (DC), 90%; disease-free survival (DFS), 82%; overall survival, 90%. In Stage III to IV patients, distant control at 3 years was 56% in patients treated with concomitant CHT only and 92% in patients treated with both induction and concomitant CHT (p = 0.014). At multivariate analysis, histology, N-stage, RT technique, and total RT dose had the strongest independent impact on DFS (p < 0.05). Induction CHT had a borderline effect on DC (p = 0.07). Most dosimetric statistics were improved in the group of patients treated with IMRT compared with conventional 3D technique. All outcome endpoints were substantially better in the study population compared with those in the previous series. CONCLUSIONS: Outcome of NPC has further improved in the study period compared with the previous decade, with a significant effect of RT technique optimization. The impact of induction CHT remains to be demonstrated in controlled trials.

Survival from salivary glands adenoid cystic carcinoma in European populations.

Adenoid cystic carcinoma (ACC) of salivary gland origin is rare. The EUROCARE data provide a good opportunity to study the survival of this uncommon cancer in a large population. A total of 2611 cases, aged 15 to 99 years, diagnosed between 1983 and 1994 with primary salivary gland ACC were analyzed. Thirty-two population based cancer registries from seventeen countries participating in EUROCARE contributed the data. Relative survival by sex, age, period of diagnosis, region, site and stage, and the adjusted relative excess risk (RER) of death were estimated. Survival since diagnosis was 94%, 78% and 65% at 1, 5 and ten years, respectively. Ten-year survival was best (69%) in patients of the youngest age group (15-54 years) and from Northern Europe (69%). In the UK was higher (65%) than in Western (62%) and Eastern (56%) Europe. ACCs in nasal cavity (RER 2.6), pharynx (RER 3.5) and larynx and bronchus (RER 3.9) had a worse prognosis compared to those of oral cavity. A strong effect of stage at diagnosis on RERs and some worsening of survival at five years over time (80% in 1983-1985, 76% in 1992-1994) were also evident. The findings of the present study, as those from clinical studies, confirm the important impact of primary site and stage at diagnosis on survival. Furthermore, we could demonstrate that survival for ACC did not improve over time and that cases from Eastern countries had a significant worse prognosis. Improvements in the disease detection in its early stage and international collaborative research should be encouraged.

Outcome of craniofacial surgery in children and adolescents with malignant tumors involving the skull base: an international collaborative study.

BACKGROUND: The aim of the study was to characterize the distribution of anterior skull base (ASB) cancers in the pediatric population and to identify predictors of outcome. METHODS: This was an international study of 1307 patients undergoing craniofacial surgery for malignant tumors; 6.4% (n = 84) among these were