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.

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.

Successful topical treatment of oral lichen planus and leukoplakias with fenretinide (4-HPR).

Eight patients with diffuse (non-operable) pre-cancerous lesions (oral lichen or leukoplakias) were treated with fenretinidec (4-HPR) applied topically twice daily. After one month of therapy two patients had complete remission and the other six had a greater than 75% response. 4-HPR was well tolerated, and no local or distant side effects were observed. Topical treatment may be combined with oral administration at lower doses to obtain therapeutic results with less toxicity than observed with oral administration alone. A study to further evaluate the efficacy of topical treatment is in progress at our institute.

Squamous-cell carcinoma of the upper lip - analysis of 123 cases.

Squamous cell carcinoma of the upper lip is rare and poorly described in the literature. We analysed retrospectively 123 cases occurring from 1929 to 1987. Greatest incidence was in the seventh decade and the M/F ratio was 2:1. Treatment was radiotherapy (36) or surgery (87). In early disease stages radiotherapy and surgery were equally effective, but in advanced disease surgery provided better results. Involved nodes indicate mandatory laterocervical submandibular lymph node dissection (bilateral for central lesions) but prophylactic dissection is inappropriate. The high frequency of relapse, tendency to plurifocality (as with all cercicofacial tumors) and risk of lymph node involvement underline the importance of regular and careful follow-up.

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.

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.

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.

Messages from completed randomized trials in head and neck cancer.

During the last three decades numerous randomized trials have been conducted in head and neck squamous cell carcinoma. The issue of pre- vs post-operative radiotherapy in advanced cancers was settled in the late 70s in favour of the latter approach and new fractionation schemes are currently being investigated, with no definite answers as yet. There is no uniform policy regarding the problem of elective neck dissection in early stage anterior oral cavity carcinoma. Often some chemotherapeutic regimen is involved in clinical trials in an attempt to improve on the standard of surgery and radiotherapy. Neoadjuvant chemotherapy has never been proven to benefit patients with advanced squamous cell carcinoma of the head and neck despite being able to decrease the rate of distant metastases. Chemotherapy given prior to or simultaneously with definite radiotherapy seems to offer the best chances for preserving vital organs, such as the larynx. Methotrexate is still the least toxic and most potent drug in recurrent or metastatic disease. The chemoprotective effect of low-dose isotretinoin on multiple primaries in the head and neck has yet to be evaluated.

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.

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.

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.

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.

Follow-up of oral leukoplakia after carbon dioxide laser surgery.

We evaluate the 3-year result of 145 oral leukoplakias operated on by outpatient carbon dioxide laser surgery at the Istituto Nazionale Tumori, Milan, Italy. The surgical technique that was used consisted of excision in 140 patients and vaporization in 5 patients. Cancer was found in 14 out of 140 patients who underwent excision (10%). In the analysis of the disease-free survival rate and of the unfavorable pattern of events, only 131 patients with benign postoperative histologic diagnosis were considered. Fifty-eight patients developed unfavorable events. The probabilities of remaining free of disease or of developing local relapses or new lesions at 3-year survival was 0.57, 0.27, and 0.19, respectively. Two patients had oral carcinomas after the operation. Forty patients modified their alcohol or tobacco habits or their teeth and/or prosthesis. Moreover, only two patients modified these factors before the unfavorable events occurred.

Outpatient surgical treatment with CO2 laser in oral cancer: immediate and long-term results.

The immediate and long-term results of excising squamous cell carcinoma of the oral cavity or lip by CO2 laser are analysed in 51 consecutive subjects treated as out-patients. From January 1982 to December 1989, 39 cases of T1 and 12 cases of small (less than 2.5 cm) non-infiltrating recurrences of squamous cell carcinoma were treated at the Istituto Nazionale Tumori in Milan. Complete removal was obtained in 44 instances, while in 7 cases cancerous margins were observed on the specimen; 5 of these underwent another wider treatment and 2 refused further therapy. Two of 39 T1 patients developed local relapses and 6/12 recurrent cancers relapsed again. Long term results are complicated by second primary cancers in 19 instances. Out-patient laser therapy is well accepted by patients and its use involves lowered direct and indirect health organisation and social costs.

CO2 laser surgery in laryngeal cancers: three year results.

The purpose of this paper is to evaluate the relapse-free survival and the overall survival at three years of 39 laryngeal cancers (10 T1 and 29 small recurrent carcinomas with mobile vocal cord) operated on by CO2 laser surgery at the Istituto Nazionale Tumori in Milan from 1982 to 1987. The 10 patients with T1 cancers had two local recurrences, whereas the 29 patients with recurrent carcinomas had 14 local recurrences. Local relapses occurred in 2/16 patients with cancer limited to the vocal cord and in 9/17 patients with glottic tumors extended to the anterior commissure or to the ventricular band or to the arytenoid. Supraglottic cancers recurred in 3/4 patients. The authors conclude that transoral laser surgery is an effective modality for treatment of T1 primary and small recurrent carcinomas of the larynx, when limited to the middle third of the vocal cord.

[Precancerous oral lesions. Diagnostic and therapeutic protocol]. / Le precancerosi orali. Protocollo di diagnosi e terapia.

The NRC (National Research Council) task force on head and neck cancer issued this document to help clinicians involved in diagnosing and treating precancerous oral diseases. Chapter 1 includes definition, epidemiology, risk factors (alcohol, smoking, poor oral hygiene), WHO classification, clinical picture of leukoplakias, erythroplasia, lichen planus, as well as their natural history. Chapter 2 points out the clinical signs to be looked for in order to make a proper diagnosis and discusses biopsy techniques. Chapter 3 deals with therapeutic procedures (surgical technique and medical treatment), while Chapter 4 concerns follow-up according to the clinical and histological diagnosis. Finally, some statistical forms are enclosed: Form 1 consists of information regarding educational qualifications, occupation, alcohol consumption, smoking and dietary habits; Form 2 consists of information about previous diseases and the history of the present disease; Form 3 records the signs and symptoms observed for the precancerous lesion; Form 4 records treatment modalities; Form 5 records patient follow-up.

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.