Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

UNLABELLED: Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.

Merkel cell carcinoma of unknown primary site.

Merkel cell carcinoma is an uncommon and aggressive primary neuroendocrine skin malignancy which mostly affects the extremities and the head and neck region of elderly patients. Merkel cell carcinoma occurs with increased frequency in sun-exposed areas, in individuals exposed to arsenic and in immunosuppressed patients. Many patients with Merkel cell carcinoma present with other malignancies, mainly skin cancers. Characteristic features are frequent recurrences and regional and distant metastases. Mortality rates range from 20 to 65 per cent. The mainstay of treatment is surgery, with wide local excision, and adjuvant radiotherapy is usually administered. Merkel cell carcinoma of unknown primary site is rare, and the majority of the few cases described have not been from head and neck areas. We present a case of Merkel cell carcinoma of unknown primary site, with upper neck and distant metastases.

Mediastinal dissection in head and neck cancer.

The superior mediastinum contains a considerable number of lymph nodes. Although occasionally involved in head and neck cancer, there are not many reports of mediastinal dissection in the practice of head and neck surgery. We present a group of seven patients with head and neck tumours that underwent mediastinal dissection in our department. Three patients are alive and free of disease six months to three years after the operation, two are alive with disease four and five years after the procedure, and two patients died peri-operatively. According to reviewed current literature, direct invasion of cancer of the head and neck to the mediastinum or mediastinal lymph node involvement is uncommon. Yet, mediastinal dissection provides the only chance for cure in selected cases.

Pretreatment prevalence of hypothyroidism in patients with head and neck carcinoma.

BACKGROUND: Hypothyroidism in the normal population age > 60 years is encountered in the range of 0.5-5% clinically, and 5-20% have subclinical hypofunction. Hypothyroidism is recognized as a common complication of treatment in patients with head and neck carcinoma (HNC) and is reported in up to 75% of patients who receive combined treatment. Surprisingly, base-line pretreatment measurements of thyroid function in large series of patients have not been reported. METHODS: Serum thyroid-stimulating hormone, free T4, and total T3 levels were recorded in 110 patients with nonthyroid HNC prior to treatment in a prospective, controlled study. RESULTS: The mean patient age (+/- standard deviation) was 65 years +/- 13.8 years, and 82% of patients had squamous cell carcinoma. A diagnosis of hypothyroidism already was established in 4.5% of patients, and subclinical hypothyroidism was discovered in an additional 6.4% of patients. Sixteen patients had other equivocal anomalies in thyroid function and were referred for further endocrine evaluation. No patients with formerly unrecognized clinical hypothyroidism were found. CONCLUSIONS: Hypothyroidism in patients with head and neck carcinoma in Israel corresponds with the reported incidence in the general population. Hypothyroidism after treatment for head and neck carcinoma stems from the effects of treatment. The need for pretreatment evaluation of thyroid function should be considered.

Upper jugular lymph nodes (submuscular recess) in non-squamous-cell cancer of the head and neck: surgical considerations.

Cervical lymphadenectomy of level II encompasses lymph nodes associated with the upper internal jugular vein and the spinal accessory nerve (SAN). Removal of tissue superior to the SAN (submuscular recess-(SMR)) was recently shown to be unwarranted in selected cases of squamous-cell cancer. Thirty-five patients with non-squamous-cell cancer (SCC) of the head and neck treated with cervical lymphadenectomy were prospectively evaluated. Thirty-seven neck dissection specimens were histologically analysed for the number of lymph nodes involved with cancer. At the time of surgery, level II was separated into the supraspinal accessory nerve component (IIa) and the component anterior to the SAN (IIb). Neck dissections were most commonly performed for cancer of the thyroid gland (19) followed in frequency by the parotid gland (seven), skin: melanoma (five), basal-cell cancer (two), and other sites (four). Twenty-five neck dissections were modified-selective procedures and 12 were either radical or modified radical neck dissection. Twenty-nine necks were clinically N+ and eight N0. Histological staging was pathologically N+ in 32 neck dissection specimens. Level IIb contained an average of 12 nodes and the IIa component contained a mean of 5.0 nodes. Level II contained metastatic disease in 28 of 32 histologically node-positive specimens (87 per cent). Level IIa was involved with cancer in six cases (16 per cent), five of which were pre-operatively staged as clinically N+. All cases (100 per cent) with level IIa involvement had level IIb positive nodes. Three of the level IIa positive cases were cancer of the parotid gland comprising 43 per cent of this sub-group of patients. Incidence of involvement of SMR in non-SCC cases is not uncommon. The additional time required and morbidity associated with dissection of the supraspinal accessory nerve component of level II are probably justified when performing neck dissection in cancer of the thyroid gland. The SMR should be excised in cancer of the parotid gland. Large-scale prospective controlled studies with long-term follow-up periods are necessary to support resection of level IIb only.

Pain in the neck after neck dissection.

BACKGROUND: Reports of disability after neck dissection have been directed toward shoulder dysfunction and pain. We could find no report addressing the issue of pain localized to the actual operative site. We have conducted a combined prospective and retrospective study of pain in patients undergoing neck dissection. METHODS: Eighty-eight disease-free patients were evaluated in 3 groups for neck pain. One group was followed up prospectively for 1 to 8 months after surgery, and 2 retrospective groups were followed up for more than 2 years or for 6 months to 2 years. Pain was assessed by a body map and visual analog scale. RESULTS: None of 31 patients followed up for more than 2 years reported neck pain. Four of 27 patients followed up for 6 to 24 months had pain, with a mean visual analog scale score of 3.7. Seventy percent of the prospective group of 30 patients had pain during the first postoperative week, and only 1 patient had pain persisting for more than 2 months. Shoulder pain and disability after radical neck dissection were encountered in all groups, comparable with the incidence reported in the literature. No postoperative neuromas were found. CONCLUSIONS: Chronic pain localized to the operative site is an uncommon occurrence even after radical neck dissection. Chronic pain in the shoulder region may follow radical neck dissection, whereas modified neck dissection is usually a painless procedure.

Intracochlear schwannoma and cochlear implantation.

A case of intracochlear schwannoma in a 58-year-old candidate for cochlear implantation is described. The tumor was located in the basal turn of the cochlea and was discovered only during surgery. Computed tomography and magnetic resonance imaging obtained prior to surgery failed to detect the tumor. Intralabyrinthine schwannomas are rare tumors that grow either in the vestibule, as intravestibular schwannomas, or in the cochlea, as intracochlear schwannomas. Complete removal of this tumor was achieved through a posterior tympanotomy approach. Cochlear implantation, which resulted in good hearing, was successfully performed 3 years later.

Delayed metastases in skin cancer of the head and neck: the case of the "known primary".

Regional metastases from head and neck cutaneous tumors are uncommon, and most present within 2 years from initial diagnosis. Occasionally such metastases may manifest at a later date, increasing the possibility of being derived from a second noncutaneous primary cancer of the head and neck region. The authors studied the course of disease in patients treated for cutaneous neoplasms manifesting with delayed regional metastases. They evaluated patients treated for cutaneous neoplasms with regional metastases presenting more than 3 years from initial treatment. There were 10 cases of squamous cell carcinoma, one case of basal cell carcinoma, and one case of basosquamous carcinoma. Mean duration from initial diagnosis to presenting neck metastases was 4 years 2 months. Mean overall follow-up is 2 years 5 months, and 3 years for patients alive without disease. Four patients died of unrelated causes and 3 patients died of their disease. Five patients are alive and free of disease. A diligent search for a second primary must always be carried out when neck metastases appear. Yet, delayed regional metastases appearing more than 3 years after resection of skin neoplasms is not uncommon and are usually associated with the primary skin cancer. Prolonged follow-up is essential, even in T1 patients. Patients with regional recurrence should be treated aggressively.

Incidence of secretory otitis media following maxillectomy.

OBJECTIVE: The purpose of this investigation was to determine the incidence and characteristics of secretory otitis media after maxillectomy procedures. STUDY DESIGN: Retrospective chart analysis was performed with the cases of 49 patients who underwent maxillectomy for tumor in the Departments of Otolaryngology-Head and Neck Surgery and Oral and Maxillofacial Surgery between the years 1990 and 1996. RESULTS: In 10 patients (20%), secretory otitis media manifested itself from 1 week to 6 months after surgery; 1 patient developed a central perforation with chronic otitis media. Nearly one third of patients who underwent total maxillectomy had secretory otitis media. Six patients (8 ears) required insertion of ventilation tubes. CONCLUSIONS: Patients undergoing total and partial maxillectomies are prone to occurrences of secretory otitis media. Insertion of ventilation tubes easily resolves the problem. Preoperative and routine postoperative patient follow-up should always include otoscopy and audiometry, and tympanometry should be performed when warranted.

Patterns of metastases to the upper jugular lymph nodes (the "submuscular recess").

BACKGROUND: Cervical lymphadenectomy to remove metastatic disease in level II encompasses lymph nodes associated with the upper third of the internal jugular vein and the adjacent spinal accessory nerve (SAN). Conservative neck dissection (ND) preserves these structures but requires manipulation of the SAN to remove tissue located in the posterosuperior aspect of level II. Limiting the dissection to the nodal group anterior to the SAN may reduce operating time and limit injury to it without compromising the removal of lymph nodes at risk for involvement with cancer. METHODS: Seventy-one patients with squamous cell carcinoma of the head and neck treated with cervical lymphadenectomy at two separate institutions were prospectively evaluated. One hundred two neck dissection specimens were histologically analyzed for number of lymph nodes present and number involved with cancer. At the time of surgery, level II was separated into the supraspinal accessory nerve component (IIa) and the component anterior to the SAN (IIb). Nodal involvement in level II was analyzed according to characteristics of the cancer at the primary site as well as nodal involvement of other levels. RESULTS: Neck dissections were most commonly done for cancer of the oral cavity (n = 33), followed in frequency by the larynx (n = 17), oropharynx (n = 7), skin of face (n = 4), unknown primary (n = 4), and other sites (n = 6). Eighty NDs were selective and 22 were either radical or modified radical NDs. Pathologic staging of the neck specimen was most commonly N0 (n = 61), followed in frequency by N1 (n= 17), N2 (n= 11), and N3 (n= 11). Data were unclear for two specimens. Level IIb contained an average of 6.9 nodes and the IIa component contained an average of 4.2 nodes. Level II contained metastatic disease in 31 of 39 node positive specimens (79%). Level IIa was involved with cancer in four cases, all of which were preoperatively staged N2 or greater. CONCLUSIONS: The additional time required and morbidity associated with dissection of the supraspinal accessory nerve component of level II may not be necessary when performing elective ND. More research with larger numbers of patients, long-term follow-up, and meticulous tissue analysis is needed to permit conclusions as to where to draw the line in determining extent of cervical lymphadenectomy.

Second primary cancer of the larynx in patients with lung cancer.

Synchronous or metachronous second primary malignancies of the lung are sometimes encountered in patients with laryngeal cancer while the occurrence of a laryngeal second primary following cancer of the lung is rare. A two-armed study was conducted. A prospective arm in which the larynges of 56 terminal lung cancer patients were examined, and a retrospective arm incorporating both a chart study of 126 terminal head and neck cancer patients (HNCP) and a computerized search of all hospital records of patients with laryngeal and lung cancers. No laryngeal malignancy was found in the lung cancer patients' group and no antedating pulmonary malignancy was recorded in the terminal HNCP. The computerized search of 1778 lung cancer patients and 213 laryngeal cancer patients also failed to demonstrate cases where the former preceded the latter. In conclusion. No second primary of the larynx was found in lung cancer patients. These results compare with reports of large databases where cancer of the larynx was found in a negligible percentage of lung cancer survivors and theories explaining this are discussed.

Pain experienced by patients with terminal head and neck carcinoma.

BACKGROUND: Pain is one of the most feared consequences of cancer and is experienced by up to 80% of patients with head and neck carcinoma (HNC). Pain in terminal HNC patients is common and often defined as severe. This study evaluated the effectiveness of the World Health Organization (WHO) analgesic ladder in the treatment of a cohort of terminal HNC patients. METHODS: The authors prospectively evaluated 62 consecutive terminal HNC patients admitted to the Chaim Sheba Medical Center Tel Hashomer Hospice or the general hospital. Data pertaining to tumor origin, spread, treatment, and results were defined. Pain was assessed with the McGill Pain Questionnaire, using a 10-point visual analogue scale (VAS) and a body map. Pain was diagnosed according to cause and type. Treatment was selected according to the guidelines provided in the WHO analgesic ladder. RESULTS: Only 10 patients suffered from pain that was not locoregional. The results of the VAS score were available in the first reading in all patients with pain (n = 48), with a mean of 4.7 (standard deviation [SD] +/- 2.0). A mean second VAS score obtained 72 hours after the first was 1.9 (SD +/- 1.1). The difference between the two scores was statistically significant (P < 0.001). A third score was available for only 6 patients, with a mean of 1.6. Only 2 patients did not experience improvement of pain after 72 hours of treatment; both of these patients had bony involvement with tumor. Thirty-one patients (65%) were diagnosed with pain of nociceptive origin; these patients were categorized as having actual nociceptive pain (22), nociceptive nerve pain (6), or referred pain to the ear (3). Nonnociceptive pain of neuropathic origin was noted for only 6 patients (12.5%). Pain that could not be well defined but was responsive to opioid analgesic treatment was noted for 11 patients. A different form of non-cancer-related pain was noted for only one patient. CONCLUSIONS: Patients were treated for pain according to the WHO analgesic ladder. They received adequate narcotic analgesics and supportive measures that allowed significant reduction of pain in nearly all cases, with acceptable side effects.

Distant metastases in terminal head and neck cancer patients.

With improved control of cancer above the clavicles, distant metastases (DM) are frequently more seen and are becoming a more common cause of morbidity and mortality. The present study defined the incidence of distant metastases in a cohort of terminal head and neck cancer patients (HNCP) and compared it to current reported data. The incidence of distant metastases in relation to the primary tumour was evaluated and their impact on survival was assessed. A retrospective survey of patient charts was made, based on the hospice database and original referring hospital charts. Data of 59 patients admitted to the hospice were evaluated. The incidence and location of locoregional and distant disease were studied and effects on survival analyzed. The overall survival from diagnosis to demise was 42.7 months. Thyroid cancer was seen in 20.3 per cent of cases and squamous cell cancer was seen in 59.3 per cent. Distant metastases were found in 83 per cent and 48.6 per cent of patients respectively. Laryngeal cancer patients had a 54.5 per cent incidence of distant metastases. Locoregional disease was seen in 47 per cent of cases and 35.7 per cent of them had distant metastases while a 64.3 per cent incidence of distant metastases was found in cases without locoregional disease. Mean survival was 47.3 months with distant metastases vs 36.5 months without metastases. The difference was not statistically significant. The incidence of distant metastases in squamous cell cancer in terminal HNCP was 48.6 per cent. This is the highest reported incidence of metastases in a clinical series. Patients without locoregional disease had almost a two-fold incidence of metastases. Survival was not affected by metastases in this series.

Home and inpatient hospice care of terminal head and neck cancer patients.

The objective is to evaluate and compare data on a cohort of terminal head and neck cancer (HNC) patients from both home and hospital-based hospice programs and to define the particular problems and needs of those patients. The setting was a tertiary academic referral centre in Tel Hashomer, Israel. We carried out a retrospective survey of patient charts based on hospice databases and death certificates of the hospital tumor registry. Charts of 102 HNC patients admitted to the hospice between 1988 and 1994 and 24 charts of HNC patients cared for by the home hospice program between 1990 and 1994 were studied. Pain, airway problems, and dysphagia were the common problems reported. A comparison of the two programs showed home hospice patients to be younger and with lower pain levels, less weight loss, and less oral candidiasis. There were fewer oral cavity tumor patients in the home hospice group. The incidence of distant metastases was in 50% range in both groups. Judging by chart entries relating to pain, airway care, and food intake, treatment protocols were effective in both programs in the alleviation of pain and other symptoms. Both programs appeared to provide adequate care for terminal HNC patients. The main difference in care between the two groups stemmed from the decisions of referring physicians and not from a predetermined level of care. The incidence of distant metastases was higher than that reported in earlier clinical series.

Anatomy of the postauricular island "revolving door" flap ("flip-flop" flap).

Reconstruction following resection of auricular (cavum conchae) lesions may be done with a retroauricular rotation flap. Recently there has been revived interest in this elegant reconstructive procedure. Although the vascular anatomy of the area was studied, no direct study of flap anatomy was reported. Six fresh adult male cadaveric dissections of the retroauricular area were performed. The skin and underlying subcutaneous tissue layer were reflected to correspond with flap size, and anatomic structures were studied. Dissection was carried out on 12 ears. The origin of the occipital belly of the occipitofrontalis muscle arising from the posterior mastoid region was identified in four patients and only as part of the fascial layer overlying the posterior mastoid region. Only a small portion of the sternocleidomastoid tendon at best is possibly incorporated in the flap. It seems that only a negligible contribution to the flap is derived from the temporalis muscle. The posterior auricular muscle was identified in all patients and its origin from the skull was (in all patients) included or bordered the posterior flap region. The posterior auricular artery (PAA) was seen in all 12 dissections. The artery was adjacent to the styloid process medial to the parotid gland superficially between the auricular cartilage and the mastoid process. The PAA was then found on the periosteum of the mastoid process, ascending deep to the posterior auricular muscle. The flap seems to be a truly fasciocutaneous flap with small, questionable, superior and anteroinferior muscular contributions, and an inclusion of the rather small posterior auricular muscle. As reported in other studies, blood supply to the area seems to be derived from the PAA.

Auricular reconstruction with a postauricular myocutaneous island flap: flip-flop flap.

Surgical defects of the concha-helix part of the ear larger than 2 cm may pose a reconstructive challenge. Split- or full-thickness skin grafts or local flaps may be used, and a number of these have been described. Yet cosmetic results are often unsatisfactory. Our experience with a postauricular myocutaneous island flap is described. Eleven patients (12 ears), aged 48 to 89 years, underwent the procedure under local anesthesia following excision of conchal bowl malignant tumors that included the cartilage underlying the skin. The surgical technique is described in detail. Few complications were encountered, and cosmetic results were excellent. In four ears, resection margins extended into the ear canal, and that portion was allowed to heal satisfactorily by secondary intention. We recommend the use of this flap for practical, safe, and early good cosmetic results.

Assessment of doxylamine influence on mixed function oxidase activity upon multiple dose oral administration to normal volunteers.

The primary purpose of this study was to assess the influence of doxylamine and phenobarbital on antipyrine/metabolites pharmacokinetics and 6 beta-hydroxycortisol urinary excretion. This study was conducted in 48 healthy male human volunteers (16 per treatment group) using a parallel study design. Treatment groups consisted of 12.5 mg of doxylamine succinate, placebo, or 30 mg of phenobarbital administered orally every 6 h for 17 days. Results indicate that no statistically significant differences were observed between the doxylamine and placebo groups that are indicative of enzyme induction. For the phenobarbital group, a significant increase for antipyrine total (36 versus 45 mL/h/kg) and nonrenal (35 versus 44 mL/h/kg) clearances and 6 beta-hydroxycortisol excretion (338 versus 529 micrograms) and a significant decrease in the terminal exponential half-life (11 versus 9 h) of antipyrine were observed.