Clinicopathological characteristics and outcome of 31 patients with ETV6-NTRK3 fusion gene confirmed (mammary analogue) secretory carcinoma of salivary glands.

OBJECTIVES: In 2010, a new subtype of salivary gland cancer (SGC), (mammary analogue) secretory carcinoma (SC), was defined, characterized by the ETV6-NTRK3 fusion gene. As clinical behavior and outcome data of this histological subtype tumor are still sparse, we aimed to describe the clinicopathological course and outcome of a series of translocation positive SC patients. PATIENT AND METHODS: We re-evaluated the pathological diagnosis of a subset of SGCs, diagnosed in 4 of 8 Dutch head and neck centers. Subsequently, tumors with a morphological resemblance to SC were tested for the ETV6-NTRK3 fusion gene using RT-PCR. Furthermore, patients prospectively diagnosed with SC were included. The clinical characteristics and outcomes were retrieved from the patient files. RESULTS: Thirty-one patients with ETV6-NTRK3 fusion gene positive SC were included. The median age was 49 years, 17 patients (55%) were male. Eighteen tumors (58%) arose in the parotid gland. One patient presented with lymph node metastasis. All patients underwent tumor resection and 4 patients had a neck dissection. Four patients had re-resection and 15 patients (48%) received postoperative radiotherapy. One patient developed a local recurrence, no regional recurrences or distant metastases were observed. After a median follow-up of 49 months the 5- and 10-year overall survival were 95%, the 5- and 10-year disease free survival were 89%. CONCLUSION: The clinical course of SC is favorable with a low rate of locoregional recurrence and excellent survival. Given the low incidence of nodal metastases, elective neck treatment, i.e. surgery and/or radiotherapy, does not seem to be indicated.

Dysphagia after an L-shaped reconstruction technique of the free jejunum graft.

BACKGROUND: The free jejunum graft is a well-established reconstruction technique after total laryngopharyngectomy. However, besides necrosis of the jejunum graft, the two most important complications are pharyngocutaneous fistula formation and dysphagia due to stricture formation. OBJECTIVES: This study aims to develop an L-shaped reconstruction technique of the free jejunum graft to decrease pharyngocutaneous fistula formation and long-term stricture formation after total laryngopharyngectomy. METHODS: An L-shaped side-to-end anastomosis was performed at the proximal end of the jejunum graft in six patients treated for piriform sinus carcinoma. Patient and operation characteristics and follow-up were recorded. RESULTS: A successful jejunum transfer was performed in all six patients. No pharyngocutaneous fistula or stricture formation occurred during a median follow-up of 23 months (range: 18-30 months). Swallowing rehabilitation started at the median 12th postoperative day (range: 5-150 days). Four patients developed dysphagia at a median of 2 months (range: 1-6 months) after oral intake was started. X-barium swallow revealed a redundant pouch of the transferred jejunum graft, which resulted in compression on the jejunum interposition during swallowing. In three patients, an operation was required to resolve these problems. After the revision operation, no dysphagia occurred during a median follow-up of 12 months (range: 7-13 months). CONCLUSIONS: Because of dysphagia complaints in the majority of our patients, we cannot recommend the described technique and should find other means to improve direct postoperative results and long-term quality of life in this difficult-to-treat group of patients.

Salvage or what follows the failure of a free jejunum transfer for reconstruction of the hypopharynx?

AIM: To analyse the cases of failure of free jejunum transfer with subsequent secondary reconstruction methods after ablative surgery for malignant tumours of the laryngopharyngeal region and the cervical oesophagus with reconstruction using a jejunum interposition. MATERIALS AND METHODS: Four cases in which failure of the jejunum interposition was managed with a second free or pedicle transfer were identified. The electronic files of patients were studied and analysed for patient characteristics and failure of reconstruction; type of salvage surgery and outcome; swallowing function and rehabilitation; postoperative complications; recurrence of tumour; patient survival and cause of death. RESULTS: Failure of the interposition occurred within 11 days in all patients, with oral bleeding being the most prominent sign. To replace the failed jejunum transfer, two new free jejunum transfers, two gastric pull-ups and one colon interposition after the second failure of a jejunum transfer were used. Three patients started swallowing rehabilitation, of which two achieved complete oral intake, defined as the redundancy of a feeding tube. The median disease-free period and overall survival was 28 and 42 months, respectively. CONCLUSION: Failure of a free jejunum transfer is a rare but inevitable complication when performed in a high-risk patient population, with oral bleeding being the most important sign of necrosis. Salvage of the buried jejunum interposition is hardly ever possible and secondary reconstruction can be performed using a new jejunum interposition or gastric pull-up procedure with considerable early postoperative complications, but relatively good results regarding swallowing rehabilitation and patient survival.

Selective neck dissection for N0 and N1 oral cavity and oropharyngeal cancer: are skip metastases a real danger?

OBJECTIVES: To contribute to insight in therapeutic safety of selective neck dissections for oral cavity and oropharyngeal cancer with a special focus on the risk of skip metastases. DESIGN: Retrospective data analysis. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 291 patients operated for oral cavity or oropharyngeal squamous cell cancer between 1999 and 2004. MAIN OUTCOME MEASURES: Incidence of skip metastases in both pathologically N0 and N+ necks for oral cavity and oropharyngeal cancer. RESULTS: Of all neck dissections (n = 226) performed for oral cavity cancer, skip metastases to level III or level IV occurred in 14 cases (6%). Ten skip metastases occurred in level III only (10/226 = 4%). Thus, four necks had metastases in level IV, which would not have been removed in case of a Selective neck dissection level I-III (supraomohyoid neck dissection). In case of oropharyngeal cancer, skip metastases to level III or level IV occurred in six of 92 cases (7%). Five skip metastases occurred in level III only (5/92 = 5%). This means that of the necks containing skip metastases, only one neck (1%): had metastases in level IV, which would not have been removed in case of a Selective neck dissection level I-III (Supraomohyoid neck dissection). CONCLUSIONS: The question whether level IV should be included in the treatment of N0 and even N1 necks of patients with cancer of the oral cavity and oropharynx cannot be answered by all data available to us now. The fear of skip metastases including level IV does not seem to be justified.

Compliance, quality of life and quantitative voice quality aspects of hands-free speech.

CONCLUSIONS: With the use of a new automatic stoma valve (ASV) it appears possible to rehabilitate patients who have previously been unsuccessful in acquiring hands-free speech. As well as making daily ASV use possible for an additional group of patients, this new device was also appreciated by many patients as an additional rehabilitation tool for specific occasions. Despite statistically significant improvements in aspects of voice and breathing using this novel ASV, improvement of peristomal adhesion is probably the main factor needed to further increase success rates. Nevertheless, our results show that it makes sense to keep trying to achieve hands-free speech, even if previous attempts have failed. OBJECTIVE: To make a long-term (6 months) assessment of compliance and aspects of voice, breathing and quality of life using a new ASV: the Provox FreeHands heat and moisture exchanger (HME). MATERIAL AND METHODS: This was a prospective clinical multicentre trial in 79 laryngectomized patients (8 regular ASV users, 58 previously unsuccessful users and 13 new users). Data were collected at baseline and after 1 and 6 months by means of European Organization for Research and Treatment of Cancer Quality of Life questionnaires and specific structured questionnaires concerning compliance, skin adhesion, voicing and pulmonary aspects. An objective assessment of voice parameters (maximum phonation time, maximum phonation time while counting, dynamic loudness range and number of pauses in a standard read-aloud text) was made for comparison of different stoma occlusion methods (digital occlusion via an HME and two different ASVs). A subjective assessment of overall voice quality was made. RESULTS: After 6 months, 19% of patients used the new ASV on a daily basis (mean 5 h/day), while 57% used it on an irregular basis as an additional rehabilitation tool for special occasions. Two-thirds of the study group indicated that they would continue to use the new ASV after the study period. With respect to the objective parameters, statistically significantly better maximum phonation times and dynamic loudness ranges were observed with the new ASV compared to the Blom-Singer ASV. However, the best results for all the objective parameters were obtained with digital occlusion via the Provox HME.

Quality of life assessment in laryngectomized individuals: do we need additions to standard questionnaires in specific clinical research projects?

OBJECTIVES: To assess, whether the EORTC questionnaires QLQ-C30 and QLQ-H&N35 give enough detailed information to study specific quality of life (QoL) related issues in laryngectomized individuals. DESIGN: Multicentre, prospective clinical trial; baseline measurement with EORTC questionnaires and an additional questionnaire, focusing on specific postlaryngectomy problems. SETTING: Head and Neck Department of one Comprehensive Cancer Center and three Academic Medical Hospitals in the Netherlands. PARTICIPANTS: Eighty laryngectomized individuals, selected to participate in a prospective clinical trial on hands-free tracheoesophageal speech. MAIN OUTCOMES MEASURES: Comparison of QoL dimensions, as assessed with the standard EORTC questionnaires, with the information obtained with additional questions, aimed at discovering in more detail, e.g. voice and respiratory problems in laryngectomized individuals. RESULTS: Based on the EORTC QoL questionnaires a good overall and voice specific QoL-level was found. However, the additional questionnaire showed that especially concerning voice and respiration more specific information was obtained. For example, despite an overall satisfaction with many aspects of the voice in more than three-quarters of the patients, speaking in a noisy environment was reported by 63% of the patients as being a serious problem, and a significant relation could be established between pulmonary and voicing problems (r = 0.28, P < 0.05), something also undetectable with the EORTC questionnaires. CONCLUSIONS: These findings underline the necessity to develop and use more specific additional questionnaires as an adjunct to the existing EORTC questionnaires, when studying specific symptoms in laryngectomized individuals, especially in order to detect intervention related changes over time.

Squamous carcinoma of the external auditory canal: a different approach.

Squamous carcinoma of the external ear canal is a rare disease and a challenge to treat. Some controversy exists regarding the best options for treatment. Reported 5-year survival varies between 35% and 63%. Since 1976, we have adopted a conservative approach to these tumours, with patients undergoing a specific protocol of meticulous tumour debulking followed by a course of repeated topical 5-fluoro-uracil (5-FU) cream application and necrotectomy. Data was collected prospectively. From 1976 to 1998, 23 patients underwent primary treatment according to our protocol. Nine patients had T1 disease whereas six had T2 and eight had T3 disease. The 5- and 10-year overall survivals were 74% and 60% respectively. These results compare very favourably with those in the literature and surgical debulking with topical 5-FU and necrotectomy remains our primary treatment of choice for squamous cell carcinoma of the external auditory canal.

CO2-laser treatment of recurrent glottic carcinoma.

BACKGROUND: Evaluation of the results of CO2 laser treatment of recurrent glottic carcinoma after radiotherapy. METHODS: Records of all patients treated in the University Hospital Rotterdam and the Dr. Daniel den Hoed Cancer Center between 1980 and 1996 by CO2 laser for recurrent glottic carcinoma were studied. RESULTS: Forty patients were treated by laser surgery. Average follow-up was 77 months. Twenty-three patients (58%) had another recurrence develop after laser surgery. Three were cured by a second laser procedure. Therefore, 20 patients (50%) were successfully treated with laser surgery. In 23 patients the recurrence did not extend into the anterior commissure; in 57% a total laryngectomy could be avoided. In 17 patients the recurrence did extend into the anterior commissure; in 41% a total laryngectomy was avoided. CONCLUSION: Most patients with recurrent carcinoma of the larynx after radiotherapy can be cured by laser surgery if the tumor does not extend into the anterior commissure.

Pulmonary function pre- and post-total laryngectomy.

Pulmonary function pre- and post-total laryngectomy was assessed in 16 patients without overt inspiratory stridor preoperatively. It could be shown that total laryngectomy is associated with a significant decrease in vital capacity and in an increase in inspiratory flow-volume values 9 days postoperatively. The inspiratory values tended to increase slightly over the next half year. The measured expiratory flow-volume values were preoperatively already significantly lower than the predicted values, and no significant changes could be observed immediately after the operation nor after 6 months. These alterations have to be taken into account when judging the pulmonary function after total laryngectomy.

Multi-institutional assessment of the Provox 2 voice prosthesis.

OBJECTIVES: To verify the initial results of a new anterograde replacement method of the second-generation indwelling Provox voice prosthesis, Provox 2 (Atos Medical AB, Hörby, Sweden), and to determine its device life. DESIGN: Nonrandomized, multi-institutional, controlled clinical trial. SETTING: Four academic hospitals and/or comprehensive cancer centers in The Netherlands. PATIENTS: Two hundred thirty-nine consecutive patients who had undergone laryngectomy and were visiting the outpatient clinic for replacement of their voice prosthesis. INTERVENTION: Anterograde replacement of the Provox 2 voice prosthesis. MAIN OUTCOME MEASURES: Evaluation of ease of use by the medical professional and appreciation by the patients, by means of structured questionnaires; comparison of device life between the original Provox and the new Provox 2 voice prosthesis in a subset of patients. RESULTS: Voice prostheses replaced were Provox (n = 188), Groningen (Medin, Groningen, The Netherlands) (n = 47), and Nijdam (Medin) (n = 4). Anterograde replacement of Provox 2 was always possible. The new anterograde method was preferred by the medical professionals in 97.1% of cases and by 93.7% of the patients, who reported significantly reduced discomfort (P<.001). There was no significant difference in device life between Provox and Provox 2 (median, 125.5 and 104 days, respectively). In 57.5% of patients, the Provox 2 device life was shorter and in 42.5% it was longer (sign test, P = .09). CONCLUSIONS: The results of the initial study concerning ease of use for the medical professionals and decreased discomfort for the patients of the new anterograde replacement procedure of the Provox 2 prosthesis were confirmed. The device life of Provox and that of Provox 2 were comparable, despite the alterations needed to optimize the Provox 2 prosthesis for the anterograde procedure.

Wound healing of cartilage structures in the head and neck region.

This study was performed to determine the various processes involved in the behaviour of hyaline cartilage during the wound healing period after trauma or surgery of vulnerable structures like the nasal septal cartilage and the cricoid. The results of different procedures (perpendicular and parallel to the cartilage surface) in young and young-adult animals were analyzed: septal incision at different locations (young-old), cricoid split (young-old), suturing cartilage, closing defects with autologous cartilage (young), biomaterials (young) and newly engineered cartilage in 4- and 24-week-old rabbits (series of ten animals). Cartilage of the young rabbit and child have similar hyaline cartilage with a varying distribution in thickness. Thinner areas are more susceptible to malformations. Incisions through younger cartilage give rise to some new cartilage formation covered by a new layer of perichondrium: through older, differentiated cartilage the incision causes superficial but permanent necrosis. Edges of cut cartilage mostly do heal by formation of fibrous junctions. This forms a weak spot, sensitive to deviations. The same fate goes for the healing between the autologous graft and the surrounding pre-existent cartilage. Trauma parallel to the surface, leads to inconsistent quantity of neocartilage. With ageing the wound healing and regenerative capacities decrease. In general, biomaterials are less accepted by the surrounding tissues and would impede further growth. Only newly engineered, and thus less differentiated (younger) cartilage of hyaline nature, appeared to be well accepted at the interface with the edges of a cartilage defect. There are indications that the release of growth factors might play a role in cartilage wound healing. In the child as well as the adult, wound healing of hyaline cartilage structures is incomplete, and surgery remains 'experimental' surgery. The clinical implications of gradual loss of the regenerative capacity of hyaline cartilage should be further investigated.

The value of ultrasound with ultrasound-guided fine-needle aspiration biopsy compared to computed tomography in the detection of regional metastases in the clinically negative neck.

PURPOSE: Head and neck oncologists have not reached consensus regarding the role of contemporary imaging techniques in the evaluation of the clinically negative neck in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to compare the accuracy of ultrasound with guided fine-needle aspiration biopsy (UGFNAB) and computed tomography (CT) in detecting lymph node metastasis in the clinically negative neck. METHODS AND MATERIALS: Sixty-four neck sides of patients with HNSCC were examined preoperatively by ultrasound/UGFNAB and CT at one of five participating tertiary care medical centers. The findings were correlated with the results of histopathologic examination of the neck specimen. RESULTS: Ultrasound with guided fine-needle aspiration biopsy was characterized by a sensitivity of 48%, specificity of 100%, and overall accuracy of 79%. Three cases had nondiagnostic aspirations using UGFNAB and were excluded. CT demonstrated a sensitivity of 54%, specificity of 92%, and overall accuracy of 77%. UGFNAB detected two additional metastases not visualized on CT, whereas CT detected no metastases not seen on UGFNAB. The results of UGFNAB were similar between the participating centers. CONCLUSIONS: Approximately one half of the clinically occult nodal metastases in our patient group were identified by both CT and UGFNAB. Overall, UGFNAB and CT demonstrated comparable accuracy. The sensitivity of CT was slightly better than UGFNAB, but the latter remained characterized by a superior specificity. The results of CT and UGFNAB did not appear to be supplementary. The choice of imaging modality for staging of the clinically negative neck depends on tumor site, T-stage, and experience and preference of the head and neck oncologist. If CT is required for staging of the primary tumor, additional staging of the neck by UGFNAB does not provide significant additional value.

Psychosocial and physical correlates of survival and recurrence in patients with head and neck carcinoma: results of a 6-year longitudinal study.

BACKGROUND: Studies that have examined correlations between psychosocial factors and survival in cancer patients do not permit any definitive conclusions. To the authors' knowledge, to date no study has examined the relation between medical as well as quality of life variables and survival in head and neck carcinoma patients. The current study focused on the complex interactions among psychosocial, medical, behavioral, and demographic variables as they relate to prognosis in these patients. METHODS: A total of 133 consecutive head and neck carcinoma patients were included in a prospective study at pretreatment. In addition to clinical variables, psychosocial and physical functioning was assessed by means of a self-report questionnaire. RESULTS: During the observation period 57 patients died whereas 76 were still alive at 6 years after treatment. Results of the multivariate survival analysis indicated that patients without head and neck metastasis had a better prognosis than patients with positive cervical lymph nodes. Pretreatment smoking showed a negative correlation with overall survival. Patients who were more physically self-efficacious (i.e., higher perceived physical abilities) were more likely to survive and less likely to develop a recurrence. In addition, patients who expressed intense psychosocial complaints prior to treatment had a better prognosis than had those who did not express such negative feelings. CONCLUSIONS: The current findings linking physical self-efficacy and prognosis are promising, but clinical trials are necessary to examine the direct and indirect mediational pathways of the variables that underlie physical efficacy and influence survival and recurrence. Also, the negative correlation between pretreatment smoking and survival suggests a need for increased efforts to address smoking in newly diagnosed patients.

A new applicator design for endocavitary brachytherapy of cancer in the nasopharynx.

INTRODUCTION: In attempting to improve local tumor control by higher doses of radiation, there has been a resurgence of interest in the implementation of brachytherapy in the management of primary and recurrent cancers of the nasopharynx. Brachytherapy with its steep dose fall-off is of particular interest because of the proximity of critical dose limiting structures. Recent developments in brachytherapy, such as the introduction of pulsed-dose-rate and high-dose-rate computerized afterloaders, have encouraged further evolution of brachytherapy techniques. MATERIALS AND METHODS: We have designed an inexpensive, re-usable and flexible silicone applicator, tailored to the shape of the soft tissues of the nasopharynx, which can be used with either low-dose-rate brachytherapy or high (pulsed)-dose-rate remote controlled afterloaders. RESULTS AND CONCLUSIONS: This Rotterdam nasopharynx applicator proved to be easy to introduce, patient friendly and can remain in situ for the duration of the treatment (2-6 days). The design, technique of application and the first consecutive 5 years of clinical experience in using this applicator are presented.

The use of confidence intervals for individual utilities: limits to formal decision analysis for treatment choice.

This paper discusses the use of confidence intervals for utility measurements. Classic test theory is applied to estimate confidence intervals for utilities. The theory is enhanced to calculate confidence areas for combined utilities and confidence bands for the threshold line. As an example it is shown that, if confidence intervals are taken into account, the implied preferred treatment of T3-larynx carcinoma patients is uncertain for a wide range of utilities, considering the mediocre reliability of most methods of utility assessment. This implies that although utility measurement and formal decision analysis can be a useful way to look at the decision problem, ambiguity, which must be resolved by other means, will often remain.

Continuity of information in cancer care: evaluation of a logbook.

A logbook, or patient-dossier, was developed, to improve continuity of information in the treatment and care of head-and-neck cancer patients. It contained information modules on different aspects of care, as well as forms to facilitate communication both between patient and care-professional and between the various care-professionals. The logbook's effectiveness was evaluated in two hospitals in Rotterdam, by comparing outcomes for trial and comparison groups of, respectively, 71 and 54 patients and 59 and 35 care-professionals. Trial patients proved to be better informed, to receive more support and to experience fewer psychosocial problems. Professionals who used the logbook were better informed about their patients, and about the care-activities of fellow-professionals than those who did not. They recognised an improvement in their contact with colleagues and in the harmonisation of their respective care-activities.

Fractionated high-dose-rate and pulsed-dose-rate brachytherapy: first clinical experience in squamous cell carcinoma of the tonsillar fossa and soft palate.

PURPOSE: Fractionated high-dose-rate (fr.HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) regimens, which simulate classical continuous low-dose-rate (LDR) interstitial radiation therapy (IRT) schedules, have been developed for clinical use. This article reports the initial results using these novel schedules in squamous cell carcinoma (SCC) of the tonsillar fossa (TF) and/or soft palate (SP). METHODS AND MATERIALS: Between 1990 and 1994, 38 patients with TF and SP tumors (5 T1, 22 T2, 10 T3, and 1 T4) were treated by fr.HDR or PDR brachytherapy, either alone or in combination with external irradiation (ERT). Half of the patients were treated with fr.HDR, which entailed twice-daily fractions of > or = 3 Gy. The other 19 patients were administered PDR, which consisted of pulses of < or = 2 Gy delivered 4-8 times/day. The median cumulative dose of IRT +/- ERT series was 66 Gy (range 55-73). The results in these patients treated by brachytherapy were compared to 72 patients with similar tumors treated in our institute with curative intent, using ERT alone. The median cumulative dose of ERT-only series was 70 Gy (range 40-77). RESULTS: Excellent locoregional control was achieved with the use of IRT +/- ERT, with only 13% (5 of 38) developing local failure, and salvage surgery being possible in three of the latter (60%). Neither BT scheme (fr.HDR vs. PDR) nor tumor site (TF vs. SP) significantly influenced local control rates. The type and severity of the side effects observed are comparable to those reported in the literature for LDR-IRT. These results contrast sharply with our ERT-only series, in which 39% of patients (28 of 72) developed local failure, with surgical salvage being possible only in three patients (11%). Taking the data set of 110 patients, in a univariate analysis IRT, T stage, N stage, overall treatment time (OTT), and BEDcor10 (biological effective dose with a correction for the OTT) were significant prognostic factors for local relapse-free survival (LRFS) and overall survival (OS) at 3 years. Using Cox proportional hazard analysis, only T stage and BEDcor10 remained significant for LRFS (p < 0.001 and 0.008, respectively), as well as for OS (p < 0.001 and 0.003, respectively). With regard to the current (IRT) and historical (ERT) series, for the LRFS at 3 years, dose-response relationships were established, significant, however, only for the BEDcor10 (p = 0.03). CONCLUSION: The 3-year LRFS of approximately 90% for TF and SP tumors reported here is comparable with the best results in the literature, particularly given the fact that 30% of the patients (11 of 38) presented with T3/4 tumors. When compared with our historical (ERT-only) controls, the patients treated with IRT had superior local control. A dose-response relationship was established for the BEDcor10.

The effects of alcohol and smoking upon the age, anatomic sites and stage in the development of cancer of the oral cavity and oropharynx in females in the south west Netherlands.

A retrospective review of 303 women, aged 40 or over, with squamous cell carcinomas of the oral cavity or oropharynx was conducted in the south-west Netherlands to study the effects of smoking and alcohol upon the age of onset, site and stage of disease. It was noted that patients presenting with oropharyngeal cancers were younger and had a higher incidence of smoking and history of heavy drinking. Age at presentation was also affected by the amount of alcohol and tobacco consumed with non-users presenting with tumors approximately 15 years later. A specific finding was that heavy drinkers and smokers tended to present with late-stage-disease.

The influence of alcohol and smoking on the incidence of oral and oropharyngeal cancer in women.

A retrospective case reference study examining the use of alcohol and tobacco in 303 women aged 40 or over suffering from oral or oropharyngeal cancer was conducted in the south-west Netherlands. Both alcohol and tobacco consumption are important in the development of oral and oropharyngeal cancer with increased consumption of both markedly increasing the risks of cancer, but alcohol having the greater effect.