Circulating fragments of cytokeratin 19 in patients with head and neck squamous cell carcinoma

In head and neck squamous cell carcinoma a reliable serum marker of carcinogenesis should be of predictive value for the development of recurrent disease or a second primary tumour. At the moment, such a tumour marker is not available. Recently, elevated levels of cytokeratin 19-fragments (Cyfra 21-1) have been detected in the serum of patients with lung cancer, in particular with squamous cell carcinoma. Cytokeratin 19 is an intermediate cell filament protein expressed in simple epithelia and their malignant counterparts. Therefore, in this prospective study, a standardized sandwich enzyme-linked immunosorbent assay for soluble cytokeratin 19 fragments was tested in the serum of 20 patients with a previously untreated head and neck squamous cell carcinoma. The results were compared with that of 20 control individuals. Our results showed significantly higher Cyfra 21-1 concentrations in the serum of patients with cancer (10.21 ± 3.03 ng/ml) than the controls (7.2 ± 2.63 ng/ml). After radical treatment the marker levels dropped significantly to 1.65+ 1.07 ng/ml. Cyfra 21-1 appears to be of value as a circulating tumour marker for head and neck squamous cell carcinoma especially in monitoring disease control.     

Isolated pulmonary nodules in head and neck cancer patients

Not infrequently, a patient with newly diagnosed head and neck cancer is noted on preoperative chest radiography to have a solitary pulmonary nodule. It is initially unclear whether the pulmonary nodule is a benign lesion or a metastatic or primary lung malignancy. Considerable controversy exists regarding the evaluation of such patients as well as the treatment, assuming that the pulmonary lesion is malignant. We have reviewed the UCLA experience with patients who had head and neck cancers and pulmonary cancers no more than 5 years apart, and reviewed the literature on early stage lung cancer. We present a rational approach to the workup and treatment of patients with head and neck cancer and a pulmonary nodule on chest radiography.     

Carcinoembryonic antigen and head and neck cancer

Carcinoembryonic antigen (CEA) concentrations were determined in the sera of 45 patients with a head and neck squamous cell carcinoma and of 13 controls. In 13 patients serial CEA measurements were made during the follow-up period. In 38% of the patients the serum CEA level was slightly elevated (greater than or equal to 2.5 ng/ml). Only 13% of the patients had clearly elevated CEA levels (greater than 5 ng/ml). CEA levels were significantly higher in patients with advanced, e.g. stage IV, disease but a correlation between serum CEA concentration and prognosis was not found. Patients who smoked had significantly higher serum CEA levels than non-smoking patients. In the serial determinations slight CEA elevations could be found in only 50% of patients with tumour recurrence. Combined with the data from the literature we conclude that serum CEA determination is not useful in predicting the outcome in patients with a head and neck squamous carcinoma.     

Head and neck cancer in cardiothoracic transplant recipients

INTRODUCTION: There is an increased incidence of cancer in patients after organ transplantation. We reviewed a large series of cardiothoracic transplant recipients to determine the incidence and natural history of head and neck malignancy. METHODS: A total of 1069 heart (n = 855), heart/lung (n = 111), and lung (n = 103) transplants were performed at Stanford University from January 1968 to February 1998. Demographic data, risk factors, and disease course were evaluated in patients who developed cancer. The mean length of follow-up was 8.9+/-5.2 years. RESULTS: One hundred twenty patients (11.2%) developed 547 non-lymphomatous malignancies. The mean number of malignancies per cancer patient was 4.6. The average time from transplantation to development of cancer was 63.1 months. A total of 50.5% of malignancies presented in the head and neck; 96.4% of these were cutaneous in origin and 3.6% were noncutaneous. Of cutaneous malignancies, 79.3% were squamous cell carcinoma and 15.9% were basal cell carcinoma Cutaneous malignancies most commonly presented on the scalp, cheek, lip, and neck. Noncutaneous malignancies involved the oral cavity (5), thyroid (4), and parotid (1). Thirteen percent of cutaneous head and neck cancers behaved aggressively, requiring extensive management including radical surgery, radiation, and/or chemotherapy. A total of 34.2% of cancer patients developed metastases and 54.9% of cancer patients died as a direct result of cancer. A total of 68% of cancer patients were smokers and 23.8% had significant alcohol use. CONCLUSION: Transplant recipients have an increased incidence of cancer presenting in the head and neck. Malignancies in transplant patients behave more aggressively than in the general population. Recognition of this aggressive biological behavior and heightened cancer surveillance should result in improved outcomes.     

Unilateral vocal cord paralysis causes contralateral false-positive positron emission tomography scans of the larynx

Positron emission tomography (PET) is used in the management of head and neck cancers. It identifies tissue with increased metabolic activity and is not specific for malignancy. A false-positive PET scan of the larynx is associated with vocal cord paralysis. We reviewed PET scan reports of patients with lung cancer from 1998 to 2001 to identify patients with increased 18-fluoro-2-deoxyglucose uptake in the larynx without a known history of head and neck cancer and then correlated this increased uptake with laryngoscopic findings. There were 17 patients who had a positive PET finding in the larynx. Fifteen of those had a false-positive PET scan in the larynx. All had contralateral vocal cord paralysis. Two patients were noted to have head and neck cancer. We conclude that vocal cord paralysis can cause a false-positive PET scan on the contralateral side of the larynx due to overactivity of laryngeal muscles that compensate for the paralyzed cord.     

De novo head and neck cancer arising in solid organ transplantation recipients: The Asan Medical Center experience

Objective

De novo cancers of head and neck area in solid organ transplantation recipients show standardized incidence ratio (SIR) of 3.8. Immunosuppression following transplantation is suggested to play as a crucial factor in pathogenesis of secondary malignancy. Prognosis of head and neck cancer arising in solid organ transplantation recipients is proven to have poor prognosis. The incidence, risk, prognosis, and survival of de novo malignancy of head and neck area in solid organ transplantation recipients in single-tertiary medical center followed up for 20 years.

Carotid rupture and tissue coverage

Carotid rupture following the treatment of head and neck malignancy is the most dreaded complication faced by the head and neck surgeon. Tissue coverage of the carotid artery has been advocated as the method of protection likely to prevent carotid rupture. A retrospective study was carried out to assess the benefit of carotid coverage and whether such protection plays a role in decreasing mortality and morbidity. A brief history of carotid protection is presented. A series of 194 head and neck cancer patients who underwent resection of their mucosal primary in continuity with radical neck dissection over a ten-year period was reviewed. No coverage was used in 120 cases, while 72 cases received carotid coverage. There was a 13% fistula rate and a 15% rate of wound complication without fistula. Six patients without recurrence who had carotid rupture or ligation for imminent rupture were identified. This group was scrutinized with regard to several parameters. Three received tissue coverage of the carotid system, while the other three were left unprotected. There was a 50% mortality rate and 25% rate of neurologic sequelae amongst the survivors. This review tends not to support the premise that tissue coverage is a major factor in the prevention of carotid rupture.     

An assessment of risk factors for the development of a second primary malignancy in the head and neck

This retrospective database study of 44,862 patients who had a history of a primary head and neck malignancy was conducted to identify any clinical variables that may predict the occurrence of a second primary head and neck malignancy. During a mean follow-up of 42.2 months, a second head and neck primary developed in 941 of these patients (2.1%). Statistical analyses revealed that a higher incidence of a second primary was associated with increased age and a location of the first primary in the larynx/hypopharynx, the oropharynx, a major salivary gland, or the nasopharynx. A lower incidence was associated with the presence of cervical nodal disease or treatment of the first primary with radiation therapy. Factors that had no effect on the risk of a second primary included sex, the size of the first primary tumor, a first-primary site in the oral cavity, and treatment of the first primary with cancer-directed surgery. The risk of a second primary head and neck cancer remained constant for at least 10 years.     

Glutathione and cisplatin resistance in head and neck cancer

Since glutathione is considered to be an important mediator of cancer cell resistance to cisplatin-based chemotherapy, we investigated glutathione in head and neck cancer by both laboratory and clinical investigations. MATERIALS AND METHODS: Intracellular glutathione concentration was measured in 7 different cell lines that originated from head and neck cancer and was correlated to their IC50 to cisplatin. Expression of gamma-glutamyl cysteine (gamma-GCS) mRNA was assessed by in situ hybridization and gamma-glutamyl transpeptidase (GGT) expression was assessed with immnunohistochemistry of 56 biopsy specimens from 51 clinical cases. Both these enzymes are important for maintenance of intracellular glutathione concentration. RESULTS: Intracellular glutathione concentration was strongly correlated with cisplatin IC50 (R2 = 0.814, P = 0.0012), suggesting that glutathione plays a major role in cisplatin resistance in head and neck cancer. High gamma-GCS expression was observed in 27 out of 47 specimens (57%), but the response rate to chemotherapy (63%) in the high expression group was not significantly different to the low expression group (P = 0.20). High GGT expression was observed in 32 out of 53 specimens (60%), but the response rate in the high GGT group was not significantly different to that of the GGT group. CONCLUSION: Although intracellular glutathione plays an important role in resistance to cisplatin in head and cancer cell lines, we failed to prove that two enzymes that contribute to the maintenance of intracellular glutathione concentration are predictive factors for the response to cisplatin-based chemotherapy. Since clinical cases are further complicated by interactions of the immune system, involvement of a variety of genes related to oncogenesis, and accompanying drugs such as 5FU, it is very difficult to determine a single factor to predict the response to cisplatin. More precise analysis is necessary to determine how head and neck cancer resists cisplatin.     

The biology of distant metastases in head and neck cancer.

The detection and treatment of metastatic cancer continues to be a challenge for the head and neck oncologist. Unfortunately, head and neck cancer patients who develop distant metastases commonly present late in their course and rapidly succumb to their disease, despite advances in imaging technologies and increased sophistication of biochemical analyses. The development of a rational approach to detection and treatment of metastatic head and neck cancers should begin with an understanding of how these tumors occur and which patients are at greatest risk for developing them. This article presents an overview of the biological processes resulting in the speed of a malignancy from one site to another, with particular attention to head and neck carcinomas. The basic histopathologic, immunology and biochemical abnormalities associated with the development of these secondary tumors are also discussed.     

Neck dissection for non-squamous malignancy

Of 1030 patients who underwent neck dissection (radical, modified or selective) in a 27-year period 103 had malignant neck nodes from a primary site in the head and neck with a histological diagnosis other than squamous carcinoma. There were 71 men and 32 women in this group with a mean age of 55 years. 28 patients had neck dissection as part of their initial treatment and 75 for later nodal recurrence. Five-year survival was 52% (40-63%). Survival was site dependent, best for thyroid tumours and worst for tumours of the major salivary glands (χ2/1 = 6.52, P < 0.05). Histology significantly affected survival, best for papillary tumours and worst for melanoma and undifferentiated tumours (χ2/1 = 3.85, P < 0.05). Survival was worse with advanced N stage but varied little with node level. The number of nodes invaded had a highly significant effect on survival (χ2/1= 23.94, P < 0.001), but extracapsular rupture had no effect. Advanced T stage at the time of surgery had a significant adverse effect on survival using univariate analysis, but this effect disappeared using multivariate analysis. In the 75 patients who had neck dissections for nodal recurrence the presence of a simultaneous recurrence at the primary site had no significant effect on survival. These patients had a better 5-year survival than patients having neck dissection for squamous disease, but the usual predictors of survival in squamous carcinoma do not always apply to non-squamous malignancy. Keywords head and neck cancer non-squamous neck dissection survival     

Autologous and heterologous blood transfusion in head and neck cancer surgery.

OBJECTIVE: To determine if the use of autologous blood ameliorates the increased risk for cancer recurrence that has been associated with perioperative blood transfusion. DESIGN: Retrospective medical record review. SETTING: Tertiary care hospital. PATIENTS: One hundred sixty-five consecutive patients with stages II to IV squamous cell carcinoma of the head and neck treated surgically at a university hospital from January 1, 1989, through December 31, 1994. MAIN OUTCOME MEASURES: We evaluated the impact of perioperative autologous and heterologous blood transfusion and 10 other variables on recurrence. Univariate and multivariate analyses were used. RESULTS: Heterologous blood recipients had a 59% recurrence rate, whereas those who had received autologous blood or no transfusion had recurrence rates of 33% and 35%, respectively. The following 4 variables had a statistically significant association with recurrence by multivariate analysis: previous treatment of current malignancy (P<.001); receipt of heterologous blood (P = .04); positive margin (P = .04); and nodal disease (P = .04). The receipt of heterologous blood was associated with a 40% increased risk for recurrence. CONCLUSION: Autologous blood products should be used during head and neck cancer surgery if possible when transfusion is necessary.     

Microvascular reconstruction after previous neck dissection

BACKGROUND: Microvascular reconstruction of defects in the head and neck is more challenging in patients who have undergone a previous neck dissection, owing to prior resection of potential cervical recipient blood vessels used for free flap perfusion. OBJECTIVE: To evaluate the reliability and safety of free flap reconstruction in patients with previous neck dissection. PATIENTS AND METHODS: Sixty free flaps were performed in 59 patients with a medical history of neck dissection for head and neck cancer. This included patients undergoing salvage surgery for recurrent cancer as well as patients undergoing secondary reconstruction of cancer surgery-related defects. Flap selection included 25 radial forearm flaps, 20 fibula flaps, 7 rectus abdominis flaps, 7 subscapular system flaps, and 1 iliac crest flap. RESULTS: Recipient vessels were used in the field of previous neck dissection in approximately half the patients with previous selective neck dissection, while contralateral recipient vessels were always used in patients with a history of modified radical or radical neck dissection. Vein grafts were not necessary in any cases. One arterial anastomosis that was created under excessive tension required urgent reoperation and revision, but there were no cases of free flap failure. CONCLUSIONS: Free flap reconstruction of the head and neck is highly successful in patients with a history of neck dissection, despite a relative paucity of potential cervical recipient blood vessels. Heavy reliance on free flaps with long vascular pedicles obviated the need to perform vein grafts in the present series, probably contributing to the absence of free flap failure. Previous neck dissection should not be considered a contraindication to microvascular reconstruction of the head and neck.     

Tumor markers in patients with head-neck carcinomas

The clinical relevance of the tumor-associated antigens SCC (squamous-cell carcinoma), CEA (carcinoembryonic antigen), and CA (carbohydrate antigen) 19-9 as tumor markers is evaluated. Twenty-six patients with squamous-cell carcinoma of the head and neck region were studied in a six-month period. Concentrations above 2 ng/ml (SCC), 5 ng/ml (CEA), and 37 U/ml (CA 19-9) are regarded as markers of abnormal activity. Elevated tumor markers were found only in 12-15%. No correlation between the serum levels and tumor localization, staging, grading, or general condition was detected for any of the markers. In the follow-up, they revealed no disease-related information despite treatment variation. The results obtained suggest that, given the present state of biochemical possibilities and considering the rather low sensitivity for head and neck cancer, the routine assessment of SCC, CEA, and CA 19-9 serum levels is of no account.     

Evaluation of chest radiography versus chest computed tomography in screening for pulmonary malignancy in advanced head and neck cancer

OBJECTIVE: To evaluate the role of chest radiography versus chest computed tomography (CT) in screening for pulmonary malignancy in advanced head and neck squamous cell carcinoma (HNSCC). DESIGN: Retrospective review of imaging. SETTING: Head and neck cancer unit. METHOD: Over a period of 1 year, 26 patients with advanced HNSCC (T3/T4) were screened for pulmonary malignancy with both chest radiography and chest CT prior to definitive therapy. OUTCOME MEASURES: Radiologic evidence of malignancy. RESULTS: Twenty patients had a normal chest radiograph and a normal CT scan. Four patients had a normal chest radiograph but an abnormal CT scan. Three of these patients had a pulmonary malignancy and one had a suspicious lesion that resolved following surgery to the index tumour. Two patients had both an abnormal chest radiograph and CT scan. One of these had a pulmonary malignancy and one had a CT-guided biopsy of the chest lesion 4 weeks postoperatively, which was normal. Chest CT scanning therefore identified three chest malignancies that would have been missed by chest radiography alone. CONCLUSIONS: Chest CT is an effective tool in screening for malignant pulmonary disease in patients with advanced head and neck cancer and should be used instead of chest radiography to avoid false-negative results.     

Squamous cell carcinoma in the immunosuppressed patient: Fanconi's anemia.

The association of immunosuppression and head and neck cancer is supported by numerous reports demonstrating impaired cell-mediated immunity, depressed T-cell function, decreased lymphocyte responsiveness, and elevated circulating immune complexes. Fanconi's anemia (FA) is a rare autosomal recessive syndrome characterized by progressive pancytopenia, skeletal abnormalities, hyperpigmentation, and other congenital anomalies. Increased chromosomal instability and defective DNA repair have been uniform findings. Several reports suggest associated immune deficiencies. There is an increased frequency of leukemia, hepatocellular carcinoma, and squamous cell carcinoma (SCC), including six cases of head and neck SCC. We reported a young girl with FA who developed SCC of the tongue. Initial studies suggest low lymphocyte counts, but normal lymphocyte responsiveness. More precise characterization of the immune system defects in malignancy prone, genetically determined syndromes may provide clues for the diagnosis and treatment of patients with the more usual but more variable risk factors for SCC of the head and neck.     

Hyercalcaemia in head and neck squamous cell carcinoma

PURPOSE OF REVIEW: Patients with advanced head and neck cancer are being treated with chemo-radiotherapy, and life is being prolonged, with or without persistent disease, for longer than was previously. Hypercalcaemia may present in patients with advanced or disseminated head and neck cancer, and, as such, these patients may present to a larger variety of clinicians for advice concerning their symptoms and illness. Modes of presentation of hypercalcaemia and treatment strategies are reviewed. RECENT FINDINGS: There were previously few large series of head and neck cancer patients diagnosed with hypercalcaemia, which may or may not have been related to their cancer being treated. Investigations, by way of blood/serum calcium level, may identify such patients. Patients with cancer-related hypercalcaemia have a poor prognosis, but many may respond temporarily to treatment when offered, with an improvement of their quality of life and death. SUMMARY: Hypercalcaemia should and must be considered in all patients who have or possibly have a diagnosis of a head and neck cancer and who present unwell with symptoms of fatigue, lethargy and somnolence. Investigation must include serum calcium (corrected for serum albumin binding) and parathyroid hormone level. Patients may be treated by a combination of rehydration and bisulphonate therapy until the serum calcium is reduced to a level below 3 mmol/l. The majority of patients diagnosed with hypercalcaemia due to head and neck malignancy die of their diseases in the short term, but some may enjoy a prolongation of life with reasonable quality if diagnosed and treated aggressively.     

Are second primary head and neck cancers with previous hematological malignancy more aggressive than de novo head and neck cancers?

ObjectivesSecondary solid tumors can occur after the treatment of hematological malignancies and are associated with a poor prognosis. We evaluated the survival outcomes of patients with second primary head and neck cancers according to the site of cancer origin, type of hematological malignancy, and age.Materials and methodsWe enrolled all patients who underwent surgery for second primary head and neck cancer and were previously treated for hematological malignancy between 1997 and 2020. We analyzed the survival outcomes of patients with second primary head and neck cancer, and compared them with 3126 de novo head and neck cancer patients diagnosed during the same period at our hospital.ResultsThe 5-year overall survival (OS) rate was significantly worse for second primary head and neck cancer patients than de novo cancer patients (52.0 % and 77.9 %, respectively; p = 0.04) and those results were similarly observed in second primary oral cavity cancer (33.3 % and 75.7 %, respectively; p < 0.01). Patients with myelodysplastic syndrome and acute myeloid leukemia showed significantly worse 5-year OS rate than those with other types of hematological malignancies (p = 0.036). Multivariate analysis showed that bone marrow transplantation (BMT) was a risk factor for the recurrence of head and neck cancers (odds ratio = 6.635, p = 0.042).ConclusionPatients with second primary head and neck cancer, particularly of the oral cavity, had a worse prognosis than patients with de novo head and neck cancer. BMT predicts recurrence in second primary head and neck cancer patients.     

Nuclear magnetic resonance spectroscopy of plasma for the detection of head and neck cancer

The plasma of 15 normal volunteers, four patients with benign head and neck disease, and 12 patients with biopsy proven head and neck malignancies were evaluated using water-suppressed nuclear magnetic resonance (NMR) spectroscopy. While the mean full width at half height (HHLW) of the NMR spectra showed a significant difference between groups (P less than .05), the predictive value of a positive test was only 57% the sensitivity was only 33%, and individual values in all groups demonstrated considerable overlap. The mean HHLW of the control group was 38.5 Hz +/- 3.5 compared with 35.2 Hz +/- 4.7 for the cancer group and 35.0 Hz +/- 10 for the benign disease group. This method was not able to distinguish patients with malignancy from those with benign disease or controls. Its use as a specific screening method for head and neck malignancy cannot be recommended.     

Squamous cell carcinoma-associated antigen (SCC) as a tumor marker in the initial diagnosis of carcinomas of the head and neck region. Results of a prospective study after 24 months

The serum--SCC antigen levels of patients with head and neck tumors were studied prospectively to determine their value in the initial diagnosis of head- and neck-cancer patients. Serum concentrations above 2 ng/ml are considered abnormal. Preliminary results of the study after a 12-month period have been reported elsewhere (1). The final results of the study show an increased percentage (53%) of pathologic findings, mostly due to the increasing number of advanced stage tumors. High serum levels were found in 60% of the T4-tumors (Fig. 4a). Well differentiated carcinomas seem to be associated with the antigen more frequently than poorly differentiated tumors (Fig. 5). SCC antigen levels were examined as many as five times before the start of treatment (85 patients), and in one-third of those cases the differences between the serum levels exceeded 1 ng/ml. As far as 85% specificity is concerned, the ROC-curve shows a sensitivity of only 40% (Fig. 2) which, in addition to the fact that the antigen was most frequently found in cases of advanced tumors, indicates that the usefulness of the SCC antigen as a tumor marker for head and neck cancer must still be regarded as low.