Adenocarcinoma of Ethmoid: a GETTEC retrospective multicenter study of 418 cases.

OBJECTIVE: To determine risk factors and evaluate the treatment of ethmoid adenocarcinoma. Epidemiologic data were recorded and compared with the literature. MATERIALS AND METHODS: A multicenter and retrospective study. The medical records of 418 patients who had presented with ethmoid adenocarcinoma at 11 French hospitals from 1976 to 2001 were analyzed to determine the clinical characteristics and treatment of the disease. RESULTS: The gender ratio was 2.8 men per 1 woman. Toxic exposure was classic for this lesion, exposure to wood and leather for most cases. The mean age was 63 years (range 31-91). Symptoms were nonspecific and based on clinical rhinologic signs. Nasal endoscopy after mucosal retraction was found useful to evaluate the extension of the lesion and to perform biopsies. Computed tomography scan and magnetic resonance imagery must be carried out prior to treatment to define extra nasal extension. The survival rate was significantly influenced by the size of the lesion (T4, N+) and extension to brain or dura. Surgery with postoperative radiotherapy remains the treatment of choice. Total excision must be a major priority, as confirmed in our series. CONCLUSION: This retrospective study was, to our knowledge, the largest ever reported in the literature. This series confirmed the risk factor of this lesion as well as the lesion's influence on the survival rate. Surgery is the most important part of the treatment. Local recurrences were responsible for the poor prognosis of this lesion.

Botulinum toxin for radiation-induced facial pain and trismus.

OBJECTIVE: To report the efficacy of botulinum toxin A for radiation-induced pain, trismus, and masticator spasm in head and neck cancer. PATIENTS AND METHODS: This prospective nonrandomized study included patients in complete remission with radiation-induced pain and trismus with or without masticator spasms. Fifty units of Botox (Allergan) or 250 units of Dysport (Ipsen) were injected transcutaneously into the masseter muscles. Jaw opening was measured and patients answered 20 questions about jaw opening, pain, and cramps, before injection at 1 month. RESULTS: Nineteen patients (7 women, 12 men) were included. Median time after radiation therapy was 5 years (range, 11 months to 22 years). At 1 month, no significant increase in jaw opening was recorded. Improvement was noted in the functional domain (P = 0.004), for pain (P = 0.002) and cramps (P = 0.004), but not in the social (P = 0.83) or emotional (P = 0.43) domains. No side effects occurred. CONCLUSIONS: Botulinum toxin did not improve trismus but significantly improved pain scores and masticator spasms (oromandibular dystonia).

Molecular detection of early-stage laryngopharyngeal squamous cell carcinomas.

PURPOSE: We sought to determine whether early-stage laryngopharyngeal squamous cell carcinomas (SCC) can be detected through molecular analysis of exfoliated cells collected with the use of a pharyngoesophageal brush (PEB). EXPERIMENTAL DESIGN: Thirty-three patients with a single, untreated, early-stage (T1 or T2) SCC of the supraglottic larynx or pharynx underwent collection of cells with a PEB, followed by endoscopic biopsy of the tumor. PEB specimens were also collected from five healthy subjects. PEB samples and tumor tissue were examined for hypermethylation of p16INK4a (CDKN2) gene promoter CpG islands (assayed by methylation-specific PCR) and UT5085 tetranucleotide microsatellite instability (assayed by GeneScan analysis). PEB samples were also subjected to cytologic analysis. RESULTS: Eight of 33 (24%) tumors exhibited a bandshift at UT5085, and 14 of 33 (42%) exhibited hypermethylation at the p16 promoter. Overall, 17 of 33 (52%) patients had at least one of the two markers in their tumor. Cytologic analysis of PEB samples revealed tumor in 4 of 33 (12%) patients; cytologic findings were normal in all five control subjects. Molecular analysis of PEB samples revealed tumor DNA in 13 of 17 (76%) patients with at least one of the two molecular markers in their tumor. Eight of 14 (57%) patients with p16 hypermethylation in their tumor and 8 of 8 (100%) patients with UT5085 microsatellite instability in their tumor had similar findings in the PEB samples. None of the PEB samples from the control subjects or patients with neither molecular marker in their tumor displayed abnormality. CONCLUSION: Molecular analysis of PEB samples holds promise for the early detection of early-stage laryngopharyngeal SCCs. New molecular markers need to be identified to increase the sensitivity of molecular screening.

Salvage surgery after failure of very accelerated radiotherapy in advanced head-and-neck squamous cell carcinoma.

PURPOSE: To assess the efficacy and toxicity of salvage surgery for local or cervical nodal recurrence after accelerated radiotherapy for locally advanced head-and-neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: We reviewed the medical records of the 136 patients with HNSCC who had been treated in three consecutive clinical trials at the Institut Gustave-Roussy using a very accelerated radiotherapy regimen (62 to 64 Gy with 2 daily fractions of 1.8 to 2 Gy over 3.5 weeks). Sixty-nine patients of the 136 initial patients (51%) had local or neck lymph nodes relapse, or both. RESULTS: Sixteen of these 69 patients (23%) had undergone salvage surgery for recurrence locally (n = 8) or in the cervical nodes (n = 8). All 16 had initially been diagnosed with locally advanced oropharyngeal carcinoma (T4, 11 patients; T3, 5 patients), and 13 had initially had cervical node involvement. After salvage surgery, 6 patients had had a local recurrence; 7, cervical node recurrence; and 3, distant metastasis. Thus, salvage surgery had been successful only in 3 patients. The 3- and 5-year overall actuarial survival rates were 20% and 11%, respectively. Eight patients had major postoperative wound complications, including carotid rupture in three cases. CONCLUSION: Salvage surgery for relapse after very accelerated radiotherapy for advanced HNSCC is infrequently feasible and is of limited survival benefit. It should be used only in carefully selected cases.

[25 years review of vascular microsurgery evaluation--perspectives]. / Les transplants libres: 25 ans de microchirurgie vasculaire--bilan--perspectives.

Free-tissue transfer has become an accepted method for reconstructing complex surgical defects. We review 25 years' experience of this approach. In France, microsurgery was first performed in 1974. I myself constructed 839 consecutive free flaps in 821 patients during a 25-year period. Here we distinguish between two different indications, namely malignant and benign lesions. In oncology, the patient recovers good quality of life even if the prognosis is poor. In contrast, the transplant offers permanent cure for patients with benign lesions. Microvascular anastomoses were constructed with separated stitches (90% of anastomoses); end-to-end anastomoses were preferred (85%). Manual suture with thread is the best technique. Post-operative flap monitoring included clinical observation, Doppler sonography, thermic probing, and endoscopy. The overall success rate of free flap reconstruction was 95.5%. In cancer patients, surviving flaps resulted in wound healing and did not delay post-operative irradiation or chemotherapy. The incidence of major complications (death 0.36%, necrosis 4.5%) and minor post operative complications (27.1%) was acceptable. The mean hospital stay was 20 days. Careful selection of the transplants yielded good reliability. Six donor sites were sufficient to reconstruct the majority of defects. Teaching of microsurgery is one of our main preoccupations. This is an indispensable technique in all fields of reconstruction. Rigorous training is necessary and much time must be spent before reaching a high level of reliability.

[Cervical cystic lymph-node metastases from epidermoid carcinoma]. / Les métastases ganglionnaires cervicales kystiques de carcinome épidermoïde.

Fifty-three cases of cystic nodal neck metastasis from squamous cell carcinoma were treated at the Institut Gustave Roussy over a 30 year period. In all cases the lesion presented as a cystic neck tumor with malignant cells found in the cyst wall on pathologic examination. A detailed physical examination of the upper aerodigestive tract mucosa revealed a small tumor located in Waldeyer's ring and often in the tonsil. Treatment consists of surgical resection of the tumor followed by external beam radiation therapy centered on the cervical lymph nodes and Waldeyer's ring. Prognosis is good, with 5-year actuarial overall survival rate of 77%.

Thyroid cartilage invasion in early-stage squamous cell carcinoma involving the anterior commissure.

BACKGROUND: Anterior commissure (AC) carcinoma is in close proximity to the thyroid cartilage. Our objective was to evaluate risk factors for thyroid cartilage invasion. METHODS: This was a retrospective study of tumors involving the AC treated by open surgery. Tumor stage, extensions, vocal fold (VF) mobility, CT scan, and pathologic cartilage status were recorded. RESULTS: Ninety-four patients with clinical T (cT) classifications cT1b (44%), cT2 (50%), and cT3 (6%) were included. The incidence of thyroid cartilage invasion was 8.5%, significantly related to VF mobility, with invasion in 31% versus 5% with normal mobility (p = .002). Sensitivity, specificity, and positive and negative predictive values for decreased VF mobility were 50%, 90%, 31%, and 95%, respectively. After a median follow-up of 49 months, there was no difference in local control between tumors with or without cartilage invasion. CONCLUSIONS: For these tumors involving the AC, VF mobility was the only significant factor related to thyroid cartilage invasion and should be taken into consideration when planning surgery.

Organ preservation surgery for laryngeal squamous cell carcinoma: low incidence of thyroid cartilage invasion.

OBJECTIVES/HYPOTHESIS: Determine the incidence and risk factors for thyroid cartilage invasion in early and midstage laryngeal cancer. STUDY DESIGN: Retrospective review. METHODS: A retrospective review was carried out of tumors treated by open surgery with at least partial resection of thyroid cartilage from 1992 to 2008. Preoperative laser, radiation therapy, or chemotherapy were excluded. Tumor stage, anterior commissure involvement, vocal fold (VF) mobility, computed tomography (CT) scan, and pathological cartilage status were recorded. RESULTS: Three hundred fifty-eight patients were treated for tumors staged cT1 (32%), cT2 (53%), and cT3 (15%) by vertical (26%), supracricoid (62%), or supraglottic partial laryngectomy (12%). The thyroid cartilage was invaded in 8.9% of cases. Abnormal VF mobility was significantly related to thyroid cartilage invasion (Fisher exact test, P = .0002). Neither anterior commissure involvement nor CT scan were related to cartilage invasion. CONCLUSIONS: Thyroid cartilage invasion was rare but increased if VF mobility was impaired. This has implications for transoral resection, which unlike open surgery avoids unnecessary cartilage resection.

Role of radiotherapy in the treatment of nasoethmoidal adenocarcinoma.

OBJECTIVE: To assess the efficacy of radiotherapy in the treatment of nasoethmoidal adenocarcinoma. DESIGN: Multicenter, retrospective study. SETTING: Eleven French hospitals. PATIENTS: The medical records of 418 patients who presented with nasoethmoidal adenocarcinoma from January 1, 1976, through December 31, 2001, were evaluated. A total of 324 patients were treated with a combination of surgery and radiotherapy, and 55 were treated with surgery only. MAIN OUTCOME MEASURES: Survival rates, disease recurrence, and postoperative complications. RESULTS: The 5-year Kaplan-Meier survey revealed survival rates of 64.5% for the surgery-only group and 70.8% for the combined-treatment group. In the surgery-only group, 28 patients (51%) had disease recurrence (24 local, 2 regional, and 2 distant). Of the 55 patients in the combined-treatment group, 31 patients (56%) had disease recurrence (29 local, 1 regional, and 1 distant). Immediate postoperative complications in the combined-treatment group were hemorrhages in 2 patients, meningitis in 3 patients, and cerebrospinal fluid leakage in 4 patients, but no deaths occurred. In the surgery-only group, 1 patient had meningitis, 2 had cerebrospinal fluid leaking but no hemorrhage, and 5 died postoperatively. CONCLUSION: The results of this retrospective study suggest that radiotherapy can be used to treat nasoethmoidal adenocarcinoma, but its usefulness should be confirmed with further prospective studies.

Cine magnetic resonance imaging with single-shot fast spin echo for evaluation of dysphagia and aspiration.

The aim of this study was to determine the feasibility of and interest in evaluation of swallowing using dynamic magnetic resonance imaging (cine-MRI) in patients with dysphagia and aspiration caused by an abnormal pharyngeal phase of swallow. A cohort of six patients previously treated for head and neck cancer with persistent dysphagia and/or aspiration were evaluated an average of 47 months after treatment. The morphology and mobility of the oral, oropharyngeal, and laryngeal structures were analyzed using cine-MRI using single-shot fast spin echo technology. The qualitative observations were compared with a clinical fiberoptic swallowing evaluation. Swallowing physiology was analyzable for dry (saliva) swallow in all patients. MRI was well-tolerated by all six patients and no clinical aspiration occurred during the MRI. In five of six cases, further information on the cause of dysphagia was obtained using cine-MRI compared with the clinical evaluation alone. In the remaining case, cine-MRI confirmed the clinical evaluation. Cine-MRI using the dry swallow technique is feasible and without risk in patients with clinical aspiration. Cine-MRI is complementary to clinical evaluation of swallowing in patients with an abnormal pharyngeal phase of swallowing resulting from treatment of cancer.

Functional results with advanced hypopharyngeal carcinoma treated with circular near-total pharyngolaryngectomy and jejunal free-flap repair.

BACKGROUND: Patients treated by a circular pharyngolaryngectomy for advanced hypopharyngeal carcinoma have a poor prognosis and disappointing speech restoration. METHODS: Three carefully selected patients underwent a near-total laryngectomy circular pharyngectomy with jejunal free flap repair and dynamic tracheopharyngeal shunt for treatment of advanced hypopharyngeal carcinoma. They received induction chemotherapy and postoperative radiotherapy. We assessed the functional outcome. RESULTS: There was no major local complication. One year after the end of radiotherapy, all patients were able to eat solid diets. Two patients were able to speak immediately after the end of the treatment. After speech re-education, a high-quality tracheopharyngeal voice was restored in all three patients. Performance Status Scale for Head and Neck Cancer Patients (PSSHN) showed a mean score equal to 81/100 at 1 year. CONCLUSIONS: In selected patients, near-total laryngectomy circular pharyngectomy with tracheopharyngeal shunt and jejunal free-flap repair offers good voice rehabilitation without impairing swallowing function.

Treatment of the N0 neck during salvage surgery after radiotherapy of head and neck squamous cell carcinoma.

BACKGROUND: The morbidity and mortality rates of salvage surgery in patients with local recurrence of head and neck squamous cell carcinoma (HNSCC) after radiotherapy are high. The aim of this study was to determine the rate of occult neck node metastasis and the surgical morbidity of patients after salvage surgery for local relapse after definitive radiotherapy. METHODS: Thirty patients who underwent salvage surgery with a simultaneous neck node dissection for a local relapse after definitive radiotherapy for HNSCC between 1992 and 2000 were included in this study. The primary tumor sites were oral cavity in six patients, oropharynx in 17, supraglottic larynx in three, and hypopharynx in four. Initially, seven patients had T2 disease, eight had T3, and 15 had T4. RESULTS: Twelve patients (40%) experienced postoperative complications, including two deaths. There was no cervical lymph node metastasis (pN0) in 29 of the 30 patients. Fifteen patients (50%) had a recurrence after salvage surgery, including 11 new local recurrences and four patients with distant metastasis. CONCLUSIONS: The risk of neck node metastasis during salvage surgery for local recurrence in patients treated initially with radiation for N0 HNSCC is low. Neck dissection should be performed in only limited area, depending on the surgical procedure used for tumor resection.

Postoperative radiotherapy for primary mucosal melanoma of the head and neck.

BACKGROUND: Primary head and neck mucosal melanoma (HNMM) has a poor prognosis with a low local control rate and frequent distant metastases. The objective of the current study was to determine the impact of postoperative radiotherapy on local control and survival. METHODS: One hundred forty-two patients with primary HNMM treated between 1979 and 1997 were reviewed. Of these, 69 patients with confirmed primary mucosal melanoma, absence of metastatic disease, and definitive management by surgery with or without postoperative radiotherapy and follow-up at the Institut Gustave-Roussy (Villejuif) were selected. The site of primary HNMM was sinonasal in 46 patients, oral in 19 patients, and pharyngolaryngeal in 4 patients. Twenty-two patients (32%) had a locally advanced tumor (T3-T4) and 17 patients had regional lymph node metastases after pathologic examination (pN > 0). Thirty patients underwent surgery alone and 39 received postoperative radiotherapy. Patients with locally advanced tumors had received postoperative radiotherapy more frequently than those with small tumors (P = 0.02). RESULTS: Thirty-seven patients (54%) experienced local disease recurrence and 47 patients (68%) developed distant metastasis. The overall survival rates were 47% at 2 years and 20% at 5 years. In the Cox multivariate analysis, patients with early T-classification tumors who received postoperative radiotherapy had a better local disease-free survival (P = 0.004 and P = 0.05, respectively) compared with patients with late T-classification tumors who did not receive postoperative radiotherapy. Patients with advanced T-classification and pN > 0 stage had a shorter distant metastasis disease-free survival compared with patients with early T-classification and pN < 0 stage. Patients with advanced T-classification tumors had a shorter overall survival compared with patients with early T-classification tumors (P = 0.003). CONCLUSIONS: The prognosis of patients with HNMM was poor. Patients had a high rate of distant metastasis and a low rate of local control. The current study suggested that postoperative radiotherapy increased local control even for patients with small tumors.

Autofluorescence videoendoscopy for photodiagnosis of head and neck squamous cell carcinoma.

The diagnosis of head and neck squamous cell carcinoma is usually made by visual identification. Searching for a non-invasive optical diagnostic method with the ability to detect the precancerous lesions or second primary tumors earlier in high-risk populations led to the development of photodiagnosis by autofluorescence (AF) endoscopy. The aim of the present study was to evaluate and discuss the diagnostic potential of autofluorescence videoendoscopy as a complementary visual aid in the routine endoscopic diagnosis of head and neck cancers. In a prospective study, 48 patients underwent white light (WL) videoendoscopy followed by AF technique at the Institute of Gustave-Roussy from November 2001 to August 2002. Of 48 patients, 30 had suspected precancerous or cancerous laryngeal lesions, 7 presented benign laryngeal lesions, while 8 showed pharyngeal and 3 oral tumors. All detected lesions were evaluated by histological examination. AF was induced by filtered blue light of a xenon short arc lamp and processed by a CCD camera system (D-Light AF System; Storz, Tuttlingen, Germany). Normal laryngeal mucosa displayed a typical green fluorescence signal. Moderate and severe epithelial dysplasia, carcinoma in situ and invasive carcinoma showed a diminished green fluorescence and presented a marked reddish-blue color. In case of hyperkeratosis a bright white color was detected. Some benign lesions, such as granulomas, polyps and papillomas also displayed altered green fluorescence. Autofluorescence videoendoscopy for photodiagnosis of head and neck squamous cell carcinomas has proved to be a method of high specificity and good sensitivity. Two additional precancerous lesions that were invisible at the WL examination but detected with the AF technique show its potential role in the regular screening procedure or follow-up examination in a high-risk population. It was a very helpful complementary visual aid for the intraoperative control of the surgical margins after per oral endoscopic resection.

T2 laryngeal carcinoma with impaired mobility: subtypes with therapeutic implications.

The aim of this study was to evaluate the outcome in the treatment of T2 laryngeal carcinoma with impaired laryngeal mobility, comparing surgical management to radiotherapy in terms of local control and survival. The files of 66 patients treated between 1988 and 1994 were retrospectively studied for tumor location, treatment and outcome. Forty-two patients were treated surgically and 24 by radiotherapy. Follow-up averaged 8.5 years. Local recurrence occurred in 12.5% of the cases treated by conservation laryngeal surgery and in 21% of the cases by radiotherapy. Ultimate laryngeal preservation was achieved in 90.9% of the cases initially treated by partial laryngectomy and in 87.5% of the cases treated by radiotherapy. Five-year actuarial survival rates were 90% and 28%, respectively. A higher rate of metastases and second primaries occurred in the group treated by radiotherapy. T2 laryngeal carcinoma amenable to partial laryngectomy had a higher local control rate than the cases not amenable to conservation surgery and treated by radiotherapy. Tumors differed in the two treatment groups in location and extensions, despite the fact that all were T2 tumors. We emphasize the limits of retrospective studies. Only prospective randomized studies will determine the true results of surgery versus radiotherapy for a homogeneous subset of T2 laryngeal tumors.

T1-T2 NO oropharyngeal cancers treated with surgery alone. A GETTEC study.

The aim of this study is to show that surgical treatment of early-stage squamous cell carcinomas of the oropharynx gives identical, if not better, oncological results than the classic radiotherapy treatment in terms of locoregional control and survival. Fifty-three patients (32 T1, 21 T2, all N0) were operated on during the years 1995-2000. Surgical treatment consisted in a resection by the transoral approach in 43 patients (81.13%); ten patients (18.87%) benefited from a pharyngectomy with (seven) or without (three) mandibular resection. A level I to V selective neck dissection was performed on 35 patients, and 5 patients underwent a level II to V selective neck dissection. The 1-, 3- and 5-year overall survival rates were 100, 94.6 and 73%, respectively. There was no significant difference concerning the tumor stage ( P=0.69), the initial localization ( P=0.64), the macroscopic aspect ( P=0.65) and the management undertaken in the different centers ( P=0.19). The 5-year rate of specific survival was 100%. The 1-, 3- and 5-year locoregional control rates were 96.22, 92.45 and 88.68, respectively. The oncological occurrences observed were 2 persistent diseases, 5 local recurrences, 11 second primary cancers and 0 nodal recurrences. Seven local failures were observed, all of which were controlled after a second treatment. Eleven patients presented second primary cancers; three died, two are alive with an extension of this second localization, and six are alive and free of disease. The locoregional control provided by surgery alone on T1-T2 N0 oropharyngeal cancers is as good as radiotherapy. Moreover surgery alone makes it possible to spare patients the complications and aftereffects of radiotherapy. It also makes it possible during the recurrences to operate on patients in non-irradiated areas with lower morbidity and mortality. It is all the more beneficial since it will be possible to resort to radiotherapy after surgery if need be.