Motor and functional recovery after neck dissection: comparison of two early physical rehabilitation programmes.

The aim of this prospective, single-centre, non-randomized explorative study is to comparatively assess two-month results of two early rehabilitation programmes in patients receiving neck dissection for head and neck cancer, with the hypothesis that those not receiving therapist-assisted physiotherapy would take an active role in their own rehabilitation to enhance outcomes. At the European Institute of Oncology, Milan (Italy), 97 patients were registered during the pre-hospitalization period and divided into an Autonomous group (living distant from the hospital) and a Physio group (living near). As expected, only 50 patients (25 per group) completed the study. Both groups received a Physical Therapy Brochure with instructions on to how to perform exercises at home. Home physical exercises started five days after surgery and continued for two months. The Autonomous group received a pre-surgery instruction session; the Physio group attended four once-weekly therapist-guided physiotherapy sessions. Two months after surgery, arm mobility and pain had recovered to pre-operative levels. Most endpoints, including the main composite, did not differ between groups. Although longer-follow-up is necessary, early physiotherapy seems to be effective in maintaining arm mobility and reducing pain, even in patients empowered to do exercises autonomously.

Identification of patients at high risk for hypocalcemia after total thyroidectomy.

Hypocalcemia is a major post-operative complication of total thyroidectomy, causing severe symptoms and increasing hospitalization time. The primary cause is secondary hypo-parathyroidism following damage to, or devascularisation of, one or more parathyroid glands during surgery. Aim of the study was to develop a simple and reliable method for predicting post-operative hypocalcemia in total thyroidectomy patients. A retrospective analysis was made of immediate pre-operative and early post-operative calcium levels in 100 patients. It was found that a marked decrease in blood calcium, immediately after surgery, was a sensitive predictor of hypocalcemia. In a subsequent prospective series of 67 patients, the efficacy was assessed of early administration of calcium plus Vitamin D in reducing symptomatic hypocalcemia in patients in whom the difference (Δ) between pre- and post-operative blood calcium was ≥ 1.1 mg/dl. This treatment was part of a protocol in which normo-calcemic patients were discharged immediately after drainage removal (third post-operative day). In the retrospective series, 84% of patients who developed hypocalcemia had Δ ≥ 1.1 and 54% of patients who did not develop hypocalcemia had Δ < 1.1 (p < 0.0001). Mean duration of hospitalization was 6.2 days. In the prospective series, 76% of patients who developed hypocalcemia had Δ ≥ 1.1 mg/dl; of the patients who did not develop hypocalcemia 75% had Δ < 1.1 mg/dl (p = 0.0013); mean hospitalization was 4.7 days (p < 0.0001). Use of the 1.1 mg/dl cut-off for deciding whether to start early prophylaxis allowed most patients to avoid symptomatic hypocalcemia (and the associated anxiety), while permitting a significantly reduced hospital stay, resulting in lower hospitalization costs.

Pregnancy and thyroid cancer: ultrasound study of foetal thyroid.

Thyroid cancer is the most common endocrine malignancy, more frequently diagnosed in young women during childbearing age and approximately 10% of all thyroid cancers are diagnosed during pregnancy or in the early post-partum period. Thyroid cancer in young people has generally an excellent prognosis, and survival among women with thyroid cancer diagnosed during pregnancy may not differ from that in age-matched non-pregnant women with similar cancer. Pregnancy after treatment of thyroid carcinoma requires both maternal and foetal controls. Of utmost importance is to ensure adequate maintenance of maternal levels of levothyroxine, needed by both the foetal central nervous system for its normal maturation and the mother to avoid possible recurrence or spread of the disease. In the present investigation, to confirm normal foetal growth and foetal thyroid development, an ultrasound study of the foetal thyroid was performed in 40 full term pregnancies in 32 women receiving levothyroxine treatment for previously treated thyroid cancer. In patients undergoing either suppressive or substitutive levothyroxine treatment, foetal thyroid growth was noted to be normal in all the cases, newborn thyroid status was always normal, and the incidence of maternal morbidity was not influenced. In the present study group, pregnancy does not appear to compromise mother's disease-free interval, nor to be compromised by thyroid cancer treatment. Results of the present study confirm that regular adjustment of levothyroxine treatment is of utmost importance for both maternal and foetal well-being and that foetal thyroid ultrasound study may add useful and reassuring data about child well-being.

Preoperative determination of serum thyroglobulin to identify patients with differentiated thyroid cancer who may present recurrence without increased thyroglobulin.

Thyroglobulin is considered a reliable marker of recurrent disease in patients with well-differentiated thyroid carcinoma. However, some patients present recurrence with no increase in serum thyroglobulin. In the attempt to identify patients who might present recurrence with no such sign of the disease, thyroglobulin levels have been determined pre-operatively in 185 consecutive patients scheduled for primary treatment for well-differentiated thyroid carcinoma from June 1997 to May 2002 at the Head and Neck Division of the European Institute of Oncology. In 22 patients (11.9% of total), serum thyroglobulin was undetectable. In none of these 22 cases was thyroglobulin detected during follow-up, either during thyroxin suppressive therapy or during withdrawal for radioiodine scan. One of these low-thyroglobulin patients developed recurrent disease involving cervical lymph nodes, with positive radioiodine scan: thyroglobulin remained undetectable. On the contrary, in the patients with high or normal thyroglobulin presenting recurrence, the recurrence was indicated, in all cases, by increased thyroglobulin levels. From these findings it may be concluded that pre-operative assessment of serum thyroglobulin may identify patients who might present recurrence without increased thyroglobulin, and in whom standard follow-up by monitoring thyroglobulin serum levels is inadequate.

Thyroid disease in northern Italian children born around the time of the Chernobyl nuclear accident.

BACKGROUND: The Chernobyl nuclear accident of 1986 caused a dramatic increase in the incidence of thyroid cancers in exposed children in Belarus. Airborne radioactivity from the reactor spread over northern Italy, where rainout gave rise to low levels of radioactivity at ground level. PATIENTS AND METHODS: As the latency between exposure to ionising radiation and development of thyroid cancer is thought to be about 10 years, in 1996/1997 all children born in 1985 and 1986 and attending school in an area of Milan, Italy were examined for thyroid nodules. A total of 3949 children were examined by two physicians blinded to the examination and diagnosis of the other. The children were to be reassessed in 2001/2002. RESULTS: In total, 1% had palpable nodules. The nodule diagnoses were: Hurtle cell adenoma (one), thyroglossal duct cyst (one), thyroid cyst (four) and thyroiditis (four). The prevalence of thyroid disease in the cohort was indistinguishable from that of populations not exposed to radioactive pollution. Only 10 children re-presented for examination 5 years later; all were negative. The direct costs of the study were estimated at 21,200 Euros. CONCLUSION: The high cost of the study in relation to reassuring lack of increase in thyroid nodule prevalence suggests that further studies are not justified.

Late solitary thyroid carcinoma metastasis to the kidney: a case report.

Secondary tumour to the kidney is quite frequent. Even if, theoretically, all solid tumours may give rise to renal metastasis, secondary lesions to the kidney occur more commonly in patients with lung and breast cancer, melanoma and lymphoma. Only 15 cases of renal metastasis arising from a follicular thyroid carcinoma have been reported in the literature. Rarely, metastases to the kidney present as primary renal tumours and may be treated surgically for that mistaken diagnosis. Nevertheless, in patients with solitary late distant metastasis of thyroid cancer, complete surgical resection may be proposed, followed by 131I ablation in order to offer a better chance of prolonged survival. We describe a case of a renal mass undergoing radical surgery and revealing itself as a solitary metastasis from follicular carcinoma of the thyroid, appearing 10 years after total thyroidectomy and 131I ablation therapy.

Blood glutathione as a surrogate marker of cancer tissue glutathione S-transferase activity in non-small cell lung cancer and squamous cell carcinoma of the head and neck.

The identification of markers predicting the response to therapy is of the utmost importance in oncology. Several authors have suggested that increased levels of glutathione (GSH) and glutathione S-transferase (GST) activity might be meaningful predictors of poor responsiveness to chemotherapy in several human cancers, but the biological assays have not been standardised and published studies show conflicting evidence. The aim of the present study was to select a validated panel of tests to assess the GST/GSH system in a clinical setting. Matched blood and tissue samples (normal and malignant) from 52 cancer patients with either non-small cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (SCCHN) were investigated. GSH levels and GST activity were higher in cancer tissues than in matched normal tissues in both malignancies. The difference was statistically significant in NSCLC (P=0.0004 and P=0.0002, for GSH and GST, respectively) and borderline in SCCHN (P=0.03 and P=0.02, for GSH and GST, respectively). Moreover a strong correlation was found between the GSH level in whole blood and GST activity in cancer tissue in both malignancies (P=0.003, r=0.53 in NSCLC, P<0.0001, r=0.89 in SCCHN). In conclusion, reliable and robust methods for routine use in tissue extracts and in whole blood have been validated. Our finding regarding the GSH level in blood indicates that circulating GSH could have a clinical relevance as a surrogate marker of GST activity in tumour tissue.

Efficacy of vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy with involved field radiotherapy in early stage (I-IIA) Hodgkin disease patients.

Vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy (CT) with involved field radiotherapy (IFRT) was first described by the Stanford group as an active regimen in early stage Hodgkin's disease (HD). Here, we report our retrospective experience of a modified VBM schedule + IFRT in a similar group of patients. From 1988, 49 patients with stage I-IIA HD received vinblastine (VBL) 6 mg/m2, bleomycin (BLM) 10 IU/m2, methotrexate (MTX) 30 mg/m2 day 1,8 every four weeks for three cycles; IFRT was delivered four weeks later followed by three additional cycles of VBM with a dose reduction of BLM (6 IU/m2). The regimen was well tolerated, with grade 3-4 neutropenia occurring in 20 patients. No acute or late pulmonary toxicity was recorded in our series. Estimated Freedom from Progression (FFP) and Overall Survival (OS) at five years are 75% (95% CI, 60.1%-92.2%) and 85% (95% CI, 73.6%-98.1%), respectively. In this retrospective analysis, VBM + IFRT treatment with bleomycin dose reduction seems safe and active. Such combination could be considered as first line treatment for early stage HD patients with favorable prognosis and/or not suitable for anthracyclines-containing regimens.

Learning curve for translaryngeal tracheotomy in head and neck surgery.

OBJECTIVES: Translaryngeal tracheotomy (TLT) is a widely accepted procedure in intensive-care units for its simplicity of execution, low morbidity, rapid wound closure after cannula removal, good esthetic results, and lack of long-term sequelae. The aim of this study was to evaluate the feasibility and use of adopting TLT in patients with cancer undergoing major head and neck surgery. STUDY DESIGN: Prospective analysis of learning curve and incidence of complications in 41 patients with cancer who underwent TLT at the Division of Head and Neck Surgery of the European Institute of Oncology from November 1997 to June 1999. METHODS: Patient characteristics, pathology, anatomic characteristics of the neck, and surgical short-term and long-term complications were noted. The patients were divided into consecutive groups of six or seven patients, and time trends in occurrence of complications and time to execute the procedure were assessed. RESULTS: TLT performance time decreased from 50 minutes in the first seven patients to 24 minutes in the last group. The technique was easy to perform and safe, with only two minor complications during surgery. However, minor complications occurred in three and major complications in 17 patients in the days immediately following surgery, almost entirely attributable to lack of counter-cannula and stylet. CONCLUSIONS: In view of the high proportion of major complications, TLT using the presently available kit is unsuitable for major head and neck surgery. However, the considerable advantages of the technique would recommend it as a valid alternative to surgical tracheotomy if the kit included a counter-cannula and stylet.

Surgical treatment of laryngeal carcinoma with subglottis involvement.

Primary cancers arising in the subglottic region are rare and are characterized by a long asymptomatic phase. More frequently the subglottis is reached by tumors arising in the glottis or even the supraglottis through invasion of the paraglottic space. Involvement of the subglottis is associated with a relatively high frequency of stomal recurrences due to a peculiar lymphatic spread to the paratracheal nodes. We analyzed a retrospective series of 68 patients with squamous cell carcinoma of the larynx extending to the subglottis region submitted to total simple laryngectomy or total laryngectomy enlarged with hemithyroidectomy and dissection of level VI nodes (HT/SPD). Overall median follow-up is 46 months. Subglottic extension was correctly diagnosed before operation in only 13/68 patients, however the resection margins, systematically determined by the pathologist, were in every case negative. Stomal relapses in laryngectomized patients without HT/SPD have been more frequent (0.55% rate per month) than in those treated with laryngectomy and HT/SPD (0.07% rate per month). It is concluded that CT should be routinely applied in preoperative staging in order to estimate the extension of the neoplasia and surgery should always include hemithyroidectomy and dissection of the homolateral paratracheal nodes when there is even minimal involvement of the subglottis. Moreover, the high incidence of second tumors in our series is noteworthy; such patients might benefit from chemopreventive therapy.

Papillary carcinoma in thyroglossal duct remnants: presentation of four cases and decision procedure for prophylactic thyroid gland dissection.

Papillary carcinoma in thyroglossal duct remnants is a rare and usually unexpected finding. It is controversial whether or not prophylactic thyroid gland dissection is necessary in such circumstances. We present our experience of four cases. Based on this, a consideration of published risk factors, and evaluation of the likelihood of a primary versus metastatic origin of the malignancy, we present a therapeutic decision procedure. When the thyroid is normal, the patient presents low-risk factors for thyroid cancer, and there is evidence that the malignancy is primary, removal of all thyroglossal duct remnants by the Sistrunk procedure is sufficient.

Is there a role for sentinel node biopsy in early N0 tongue tumors?

BACKGROUND: Detecting metastases to the cervical lymph nodes is the main problem in the management of squamous cell carcinoma of the tongue. We investigated the ability of sentinel node (SN) biopsy to predict neck status in 11 patients with lateral T1-T2, N0, and M0 squamous cell carcinoma of the tongue who underwent ipsilateral neck dissection 30 to 40 days after primary surgery. METHODS: In 5 patients, technetium 99m-labeled particles were injected close to the operation scar on the day before neck dissection, and the labeled neck nodes were revealed by lymphoscintigraphy. The next 6 patients underwent lymphoscintigraphy both before surgery and before neck dissection. During neck dissection, the ipsilateral SNs were identified by using a hand-held probe and removed separately. RESULTS: Three patients (27%) had metastatic neck nodes. In all cases, labeled nodes were revealed by scintigraphy. Ipsilateral SNs were removed from 8 patients and correctly predicted the state of the neck (6 negatives and 2 positives). Lymphoscintigraphy before and after surgery revealed that drainage was modified after surgery in 5 of 6 patients; the pre-surgery drainage pattern varied markedly among the 5 pN0 patients. CONCLUSIONS: The technique allows easy and safe identification of SNs and shows promise in guiding selective neck dissection. Surgery on the primary tumor often modifies lymphatic drainage, so that SN biopsy may only be useful if the primary operation and neck dissection are performed at the same time.

Surfing prognostic factors in head and neck cancer at the millennium.

The ability to reliably predict cancer outcome could tailor therapy to the aggressiveness of the tumour to achieve the best results in terms of loco-regional control, overall survival and quality of life. Retrospective and prospective clinical trials involving large series of patients have validated some predictive clinical and pathological factors, whereas the utility of many other prognostic factors has not been established. This has led to some confusion in clinical practice. In order to clarify the significance, role and cost of these prognostic factors we carried out a Medline search of all papers published between 1993 and 1998 concerning the reliability and cost of markers with prognostic significance, in head and neck squamous cell carcinoma, and assessed the results according to a number of criteria relating to reliability and cost. Regarding reliability we classified prognostic factors into: (1) those with a proven significance based on the fact that they were unanimously reported as having an independent statistical correlation with outcome and prognosis; and (2) those for which results were not unanimous, and which significance is still controversial. Cost analysis showed a substantial difference between validated tests which are of low cost and experimental tests which are expensive. Based on these data regarding both the reliability and cost of each prognostic factor, we propose guidelines for their use in clinical practice in the year 2000.

Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer. A pilot study.

PURPOSE: To evaluate the feasibility of induction chemotherapy followed by concomitant chemotherapy and hyperfractionated irradiation in locally advanced, inoperable head and neck cancer. METHODS: A pilot study was undertaken comprising 3 cycles of cisplatinum (100 mg/m2, day 1) and 5-fluorouracil (1000 mg/m2 in continuous intravenous infusion over the first 120 h) followed by bifractionated radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant weekly cisplatinum infusion (50 mg/m2). RESULTS: Six patients were enrolled in the study. All of them completed the protocol therapy. Severe mucositis and myelotoxicity were the most common acute side effects observed in all and in 5 of the patients, respectively. Acute toxicity required interruption of concomitant chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary. Opioid analgesic parenteral therapy was administered in 4 patients. Three of them had to be hospitalized. One patient experienced cerebral stroke 1 day after the completion of therapy and died 7 days later. Due to high acute toxicity, patient accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4 patients are alive, 3 of them are free of disease and in 1 local progression has been diagnosed. CONCLUSIONS: High acute toxicity of induction cisplatinum and 5-fluorouracil followed by concomitant cisplatinum and hyperfractionated irradiation calls for less toxic treatment schedules in locally advanced inoperable head and neck cancer.

Combined treatment of advanced oropharyngeal cancer with external radiotherapy and three-step radioimmunotherapy.

The prognosis of patients with locally advanced head and neck cancer remains grim due to poor locoregional tumour control. In the attempt to eradicate residual disease, various novel modalities have been tested, among which radioimmunotherapy (RIT) has shown some potential. We present a case of locally advanced oropharyngeal carcinoma successfully treated with a combination of various treatments including surgery, radio-chemotherapy and three-step RIT, with the avidin-biotin pretargeting system. A partial tumour response was achieved after surgery and radio-chemotherapy; persistent disease was documented at computed tomography (CT), ultrasound (US) and immunoscintigraphy (ISG) 10 weeks after the end of chemo-radiotherapy. The good correlation between the tracer localization in the scintigraphic images and residual mass visualized at CT suggested the application of three-step RIT using systemic administration of yttrium-90 (py) biotin. At present, 17 months after RIT, the patient is alive with no evidence of disease as documented by magnetic resonance imaging (MRI) and US. This is the first case of complete clinical remission of a head and neck carcinoma induced by combined treatment including pretargeted RIT with 90Y-biotin.

Prognostic factors in head and neck oncology: a critical appraisal for use in clinical practice.

BACKGROUND: An ideal prognostic factor would provide information about the biological behaviour of a tumour, permitting the prediction of the outcome and response to therapy. Nowadays there is a considerable confusion concerning the value, significance and use of the know prognostic factors in head and neck cancer. MATERIAL AND METHODS: A meta-analysis of works published in literature between 1993 and August 1997 on prognostic factors in head and neck oncology was carried out. RESULTS: Prognostic factors were analysed and classified according to Wennenberg in the following groups: patient-related factors, tumour-related factors and factors predicting response to therapy. CONCLUSIONS: We propose a classification of prognostic factors in head and neck cancer according to their significance and reliability: factors of proven significance and experimental factors. This classification might be useful to select guidelines to use in clinical practice.