Predictors and timing of recovery in patients with immediate facial nerve dysfunction after parotidectomy.

BACKGROUND: Identification of predictors for permanent facial nerve dysfunction and timing of recovery are important for the management of patients who experience immediate facial nerve dysfunction after parotidectomy. METHODS: In this 6-year retrospective cohort study, 54 such patients were analyzed to determine the associated prognostic factors and timing of recovery. RESULTS: All 54 patients with immediate postparotidectomy facial nerve dysfunction experienced weakness of the marginal mandibular branch; 7% had coexisting zygomatic branch dysfunction. Forty-five patients (83%) achieved complete recovery. The cumulative rates of recovery at 1 month, 3 months, 6 months, and 1 year postparotidectomy were 31%, 70%, 81%, and 83%, respectively. Immediate postparotidectomy facial nerve dysfunction higher than House-Brackmann (H-B) grade III was the only poor prognostic factor (odds ratio, 6.6; 95% confidence interval, 1.2-35.4). Advanced age, malignant tumor, larger tumor size, and postoperative steroids did not exert significant effect on the recovery of facial nerve dysfunction. CONCLUSION: Immediate postparotidectomy facial nerve dysfunction greater than H-B grade III was a significant predictor of permanent dysfunction. Only 2% of patients achieved any improvement beyond 6 months postoperatively.

Treatment selection for tonsillar squamous cell carcinoma.

BACKGROUND: The optimal treatment for tonsillar squamous cell carcinoma (SCC) remains controversial. The purpose of this study was to evaluate long-term treatment outcomes of patients with tonsillar SCC, in order to aid in appropriate treatment selection. METHODS: We conducted a retrospective chart review of 105 patients with curatively treated tonsillar SCC between January 1996 and December 2005. Forty-three patients (41.0%) underwent primary surgery with or without adjuvant therapy (primary surgery group), and 62 patients (59.0%) were treated with radiotherapy/chemoradiotherapy (RT/CRT, organ preservation group). Twenty patients (19%) received tumor tonsillectomy before definitive RT/CRT and were grouped into the organ preservation group. RESULTS: No significant differences were observed between the primary surgery and organ preservation groups in terms of local control (p = 0.212), regional control (p = 0.684), distant metastasis (p = 0.627), 5-year disease-specific survival (DSS, p = 0.774), and overall survival rates (OS, p = 0.667). The rates of major complication (p = 0.216), long-term dependency on feeding tubes (p = 0.876), and tracheostomy (p = 0.401) were also similar. Advanced T classification (T3-4) was the only factor associated with significantly worse DSS (p = 0.007) and OS (p = 0.012). However, there was also no difference in final treatment outcomes in T3-4 patients regardless of whether they were treated with primary surgery or RT/CRT. In the organ preservation group, tumor tonsillectomy before RT/CRT did not improve local control (p = 0.520) or other treatment outcomes, including 5-year DSS (p = 0.707) and OS (p = 0.745). CONCLUSION: Both primary surgery and RT/CRT organ preservation are effective treatments for tonsillar SCC. Single modality treatment, either surgery or RT/CRT, can typically be provided for stage I-II diseases. Although RT/CRT organ preservation is used more frequently for stage III-IV tonsillar SCC in recent years, primary surgery combined with adjuvant therapy still achieves equivalent outcomes. Multidisciplinary pretreatment counseling and the facilities and personnel available are therefore important for decision-making. In addition, if RT/CRT organ preservation is selected as the primary treatment, tumor tonsillectomy is not indicated.

Role of TRPA1 and TRPV1 in the ROS-dependent sensory irritation of superior laryngeal capsaicin-sensitive afferents by cigarette smoke in anesthetized rats.

BACKGROUND: Laryngeal exposure to cigarette smoke (CS) evokes sensory irritation, but the mechanisms are largely unclear. The TRPA1 and TRPV1 receptors are two types of Ca(2+)-permeant channels located at the terminals of airway capsaicin-sensitive afferents. We investigated the mechanisms underlying the airway reflex evoked by laryngeal CS exposure in anesthetized rats. METHODS: CS (7 ml) was delivered into a functionally isolated larynx, while the animals (n = 201) breathed spontaneously. Respiratory parameters were measured. All use of pharmacological agents involved pretreatment by laryngeal application. RESULTS: Laryngeal CS exposure immediately evoked a concentration-dependant apneic response that was unrelated to the nicotine content of the CS. This inhibition of breathing was abolished by bilateral sectioning of the superior laryngeal nerves (SLNs) or by perineural capsaicin treatment of the SLNs (selective blocking of capsaicin-sensitive afferent neural conduction), suggesting the involvement of superior laryngeal capsaicin-sensitive afferents in the reflex. The reflex apnea was significantly attenuated by N-acetyl-l-cysteine (antioxidant), EGTA (extracellular Ca(2+) chelator) and BAPTA-AM (intracellular Ca(2+) chelator), indicating the importance of reactive oxygen species (ROS) and Ca(2+). This reflex apnea was also partially reduced by HC030031 (TRPA1 receptor antagonist) and capsazepine (TRPV1 receptor antagonist), and was nearly abolished by a combination of these two antagonists, suggesting a central role for the TRPA1 and TRPV1 receptors. Furthermore, the reflex apnea was attenuated by indomethacin (cyclooxygenase inhibitor); however, the attenuation by indomethacin was not increased by pretreatment with HC030031 or capsazepine, indicating that TRPA1 and TRPV1 receptor functionality is, at least in part, linked to cyclooxygenase metabolites. CONCLUSIONS: The reflex apnea evoked by laryngeal CS requires activation of both TRPA1 and TRPV1 receptors, which are likely to be located at the terminals of superior laryngeal capsaicin-sensitive afferents. Laryngeal sensory irritation by CS seems to depend on the actions of ROS and cyclooxygenase metabolites on these two types of receptors.

Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma.

BACKGROUND: Risks of perineural invasion (PNI) in T1-2 oral tongue squamous cell carcinoma (SCC) have not been specifically elucidated. METHODS: Pathological features, including PNI, were re-reviewed under regular hematoxylin-eosin staining in 190 patients with T1-2 oral tongue SCC. RESULTS: Tumor thickness >5 mm, PNI(+), and lymphovascular invasion (+) independently predicted lymph node involvement. PNI(+) and neck observation also independently predicted neck recurrence, but only PNI(+) was associated with a poor disease-specific survival (DSS; p = .003). In patients who were clinically node negative (cN0), elective neck dissection contributed to a better DSS in patients with PNI(+) tumors (p = .046), but not in patients with PNI (-) tumors (p = .809). Additionally, increased tumor thickness predicted the presence of PNI. CONCLUSION: PNI is a crucial pathological feature for T1-2 oral tongue SCC. Elective neck dissection should be performed in patients who were cN0 with PNI. Careful evaluation for PNI should be advocated in regular pathological diagnosis.

There is no structural relationship between nasal septal deviation, concha bullosa, and paranasal sinus fungus balls.

This study aims to determine the relationship between nasal septal deviation, concha bullosa, and chronic rhinosinusitis by using a definitive pathological and simplified model. Fifty-two consecutive sinus computed tomography scans were performed on patients who received endoscopic sinus surgery and whose final diagnosis was paranasal sinus fungus balls. The incidences of nasal septal deviation and concha bullosa for patients diagnosed with paranasal sinus fungus balls among the study group were 42.3% and 25%, respectively. About 63.6% sinuses with fungus balls were located on the ipsilateral side of the nasal septal deviation, and 46.2% were located on the ipsilateral side of the concha bullosa. When examined by Pearson's chi-square test and the chi-squared goodness-of-fit test, no significant statistical difference for the presence of paranasal sinus fungus balls between ipsilateral and contralateral sides of nasal septal deviation and concha bullosa was noted (P = 0.292 and P = 0.593, resp.). In conclusion, we could not demonstrate any statistically significant correlation between the location of infected paranasal sinus, the direction of nasal septal deviation, and the location of concha bullosa, in location-limited rhinosinusitis lesions such as paranasal sinus fungal balls. We conclude that the anatomical variants discussed herein do not predispose patients to rhinosinusitis.

Effectiveness of narrow band imaging in patients with oral squamous cell carcinoma after treatment.

BACKGROUND: We evaluated the effectiveness of narrow band imaging (NBI) in patients with oral squamous cell carcinoma (OSCC) after treatment. METHODS: In all, 101 consecutive OSCC patients underwent NBI examination for posttreatment follow-up. Four patients had local recurrence. Twenty-six second primary malignancies were found in 18 patients; 6 patients (33%) had more than 1 lesion. Seventeen lesions (65%) were carcinoma in situ or severe dysplasia. Most of them occurred in the oral cavity (77%). RESULTS: A higher incidence (18% vs 9%, p = .037) and less-advanced stage (4% vs 37%, p = .0005) of second primary malignancies were found among the NBI group compared with a previous cohort without NBI examination, and fewer patients needed postoperative adjuvant therapy (12% vs 50%, p = .0005). CONCLUSIONS: NBI is an effective method to identify early lesions in the head and neck area, especially the oral cavity, among patients with OSCC after treatment.

Treatment for T1-2 oral squamous cell carcinoma with or without perineural invasion: neck dissection and postoperative adjuvant therapy.

BACKGROUND: Although perineural invasion (PNI) has been a poor prognostic factor for head and neck cancers, few studies have focused on oral squamous cell carcinoma (OSCC). The independent significance of PNI in early T1-2 OSCC and the benefit of treatment modification based on PNI status have not been assessed. This study investigated the role of PNI in T1-2 OSCC patients, with focus on the controversial issues of neck management and postoperative adjuvant therapy. METHODS: PNI status was re-reviewed under hematoxylin and eosin staining in tumors of 307 consecutive T1-2 OSCC patients. Oncologic and survival outcomes were analyzed by univariate and multivariate analyses. RESULTS: PNI was identified in 84 (27.4%) patients, correlating with several established poor prognostic factors. In multivariate analysis, PNI remained an independent predictor for neck metastasis, neck recurrence, and a worse 5-year disease-specific survival. Elective neck dissection contributed to a significantly better 5-year disease-specific survival only in cN0 patients with PNI-positive tumors (P = 0.0071) but not in those with PNI-negative tumors (P = 0.3566). In low-risk patients who were treated by surgery alone, including neck dissection, the 5-year disease-specific survival rates were almost the same in those with PNI-positive tumors and those with PNI-negative tumors (92.0 vs. 92.9%; P = 0.9104). CONCLUSIONS: Elective neck dissection is indicated for cN0 patients with PNI-positive tumors for the efficacy of improving disease-specific survival as well as neck control. However, low-risk PNI-positive patients who undergo neck dissection do not need postoperative adjuvant therapy, because the residual risk from PNI is minimal.

Promising long-term results with attenuated adverse effects by methotrexate-containing sequential chemoradiation therapy in locally advanced head and neck squamous cell carcinoma.

OBJECTIVE: To reduce severe acute and late toxicities without compromising organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin-fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation. METHODS: Two induction courses of methotrexate (40 mg/m(2)/day, days 1, 8 and 15), cisplatin and 5-fluorouracil (25 and 750 mg/m(2)/day, days 1-4) were given in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head and neck squamous cell carcinoma. Responders received concurrent chemoradiation with weekly cisplatin (20 mg/m(2)/day) and 5-fluorouracil (400 mg/m(2)/day) on day 1. RESULTS: Among 57 patients (58% with Stage IV and hypopharyngeal cancer), the rates of Grade 3-4 toxicity were 30 and 74% during induction and CCRT, respectively. A total of 49 patients completed induction and began concurrent chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up of 62 months (range 19-83 months) for the current survivors, the 3-year overall and disease-specific survival estimates were 50 and 58%, respectively. The 3-year organ preservation survival was 74% in patients who achieved complete remission after concurrent chemoradiation, and 96% of current survivors are tracheotomy and feeding tube-free. No patient without local/regional failure suffered from distant metastasis. CONCLUSIONS: Methotrexate-cisplatin-fluorouracil induction chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation is an acute and late toxicity-acceptable protocol without attenuating organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma. In this patient cohort with advanced head and neck squamous cell carcinoma, overall and organ preservation survivals were encouraging, and provided promising long-term benefits of this approach.

The basis of preoperative vocal fold paralysis in a series of patients undergoing thyroid surgery: the preponderance of benign thyroid disease.

BACKGROUND: Preoperative vocal fold paralysis (VFP) is thought to be rare in patients with benign thyroid disease (BTD). In contrast with cases of malignancy, in which the recurrent laryngeal nerve (RLN) should be severed, in patients with BTD and VFP the RLN can be preserved without threatening patients' lives. This study investigates the clinical features that enable identification of patients who have VFP associated with BTD. METHODS: Medical records of 187 consecutive patients who underwent thyroid surgery were retrospectively reviewed. The association between preoperative VFP and pathology (benign or malignant), clinical features, and treatment results of patients with BTD and VFP were analyzed. RESULTS: Of the 187 patients, 145 patients had BTD and 8 of these cases (5.52%) had preoperative unilateral VFP. The prevalence of BTD with VFP was 4.3% (8/187). The other 42 patients had malignant thyroid disease and 4 of these cases (9.52%) had preoperative unilateral VFP. None of the aforementioned VFP was caused by previous thyroidectomy or surgery to the neck. Although the relative risk of VFP in patients with thyroid malignancy was 1.726 (9.52%/5.52%), there was no significant association between VFP and malignancy. Of the eight patients with BTD, benign fine-needle aspiration cytology or frozen sections, goiter with a diameter larger than 5 cm, cystic changes, and significant radiologic tracheo-esophageal groove compression were the common findings. During thyroidectomy, the RLN was injured but repaired in three patients. Two events occurred in patients who had severe RLN adhesion to the tumor caused by thyroidectomy performed decades ago. Two of the five patients without nerve injury recovered vocal fold function. The overall VFP recovery rate for patients with BTD and VFP was 25% (2/8). CONCLUSIONS: Preoperative unilateral VFP is not uncommon in thyroid surgery. Obtaining information on laryngeal function is of extreme importance when planning surgery, especially contralateral surgery. Goiter with preoperative VFP is not necessarily an indicator of malignancy. Benign perioperative cytopathologic findings with typical radiographic compression strongly suggest that VFP is caused by BTD. If, during thyroidectomy, the RLN is carefully preserved, recovery of vocal fold function may still be possible.

Management of base of tongue squamous cell carcinoma: experience with 85 patients in Taipei Veterans General Hospital.

BACKGROUND: The optimal treatment of base of tongue squamous cell carcinoma (BOTSCC) remains controversial. To optimize treatment planning, this study analyzed the outcomes of patients with BOTSCC treated in Taipei Veterans General Hospital. METHODS: Retrospective chart reviews were performed for 107 patients with BOTSCC from January 1990 to December 2004, and 85 patients were included, with a mean follow-up interval of 38 months. Patients were divided into surgical and radiotherapy/chemoradiation therapy (RT/CRT) groups. Potentially significant variables for survival were analyzed. RESULTS: The 3-year overall survival (OS) and disease-free survival rates were 40% and 37.1%, respectively. No significant differences in the patient and disease characteristics between the surgical (n = 39) and RT/CRT groups (n = 46) were found. Advanced overall stage (p = 0.034), cervical lymph node metastasis (p = 0.007), and regional recurrence (p = 0.024) were poor prognostic factors for OS. In early-stage disease (Stages I and II), the 3-year OS was higher in the surgical group (68.6%) than in the RT/CRT group (37.5%), but the significance was only borderline (p = 0.071). There was no significant difference in the 3-year OS between the patients in the surgical and CT/CRT groups with advanced-stage disease. In the surgical group, lymphovascular permeation (p = 0.015) and soft-tissue involvement (p = 0.01), determined by pathologic examination, were poor prognostic factors for OS. Recurrence occurred in 35 patients (41.2%), with no significant difference in local, regional, or distant control between the surgical and RT/CRT groups. CONCLUSION: These findings emphasize the importance of neck disease control in the treatment of BOTSCC. Although currently, RT/CRT is used more frequently, surgery may still have a role in the treatment of early-stage disease. Both surgery with adjuvant therapy and RT/CRT produced equivalent survival rates in the treatment of advanced-stage disease, but the recurrence rate was unsatisfactory. A more effective treatment modality with less early and late toxicity is needed.

Persistent Krüppel-like factor 4 expression predicts progression and poor prognosis of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one prevalent human cancer worldwide. No molecular markers are presently used for predicting prognosis in HNSCC. Krüppel-like factor 4 (KLF4) is a transcription factor with diverse physiological functions, and possesses opposing roles in different human cancers. The expression and roles of KLF4 in HNSCC remain to be elucidated. In this study, immunohistochemical (IHC) analysis of KLF4 in 62 HNSCC was firstly performed. IHC results demonstrated that 42 (67.7%) had decreased KLF4 expression compared with surrounding normal epithelium, while persistent KLF4 expression was demonstrated in 20 (32.3%). The IHC results were further verified by Western blot and real-time PCR analyses to confirm the robustness of staining and interpretation. Interestingly, persistent KLF4 expression independently correlated with a worse disease-specific survival (P = 0.005), especially in patients with advanced disease. In consistent with clinical observation, all five HNSCC cell lines tested revealed a low level of baseline KLF4 expression. Moreover, enforced KLF4 expression in cell line SAS significantly increased in vitro migration/invasion abilities, multi-drug resistance, and in vivo tumorigenicity. These results clearly illustrate that persistent KLF4 expression predicts poor prognosis and confers aggressiveness in HNSCC. Our data therefore provides valuable information that HNSCC with persistent KLF4 expression might require intensified combination treatment in future practice.

Regulation of excision repair cross-complementation group 1 by Snail contributes to cisplatin resistance in head and neck cancer.

PURPOSE: We investigated the mechanism and clinical significance of the epithelial-mesenchymal transition (EMT)-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC). EXPERIMENTAL DESIGN: The correlation between the expression of different EMT regulators and chemoresistance genes, such as excision repair cross complementation group 1 (ERCC1), was evaluated in cancer cell lines from the NCI-60 database and four human HNSCC cell lines. Ectopic expression of Snail or short-interference RNA-mediated repression of Snail or ERCC1 was done in HNSCC cell lines. Cell viability was examined for cells after cisplatin treatment. A luciferase reporter assay and chromatin immunoprecipitation were used to identify the transcriptional regulation of ERCC1 by Snail. Immunohistochemical analysis of Snail, Twist1, ERCC1, hypoxia inducible factor-1 α (HIF-1α), and NBS1 were done in samples from 72 HNSCC patients receiving cisplatin-based chemotherapy. RESULTS: The correlation between the expression of Snail and ERCC1 was confirmed in different cell lines, including HNSCC cells. In HNSCC cell lines, overexpression of Snail in the low endogenous Snail/ERCC1 cell lines FaDu or CAL-27 increased ERCC1 expression, and hypoxia or overexpression of NBS1 also upregulated ERCC1. Knockdown of Snail in the high endogenous Snail/ERCC1 cell line OECM-1 downregulated ERCC1 expression and attenuated cisplatin resistance. Furthermore, suppression of ERCC1 in Snail- or NBS1-overexpressing HNSCC cells enhanced sensitivity to cisplatin. Snail directly regulated ERCC1 transcription. In patients with HNSCC, coexpression of Snail and ERCC1 correlated with cisplatin resistance and a poor prognosis. CONCLUSIONS: Activation of ERCC1 by Snail is critical in the generation of cisplatin resistance of HNSCC cells.

Promising overall survival of patients with recurrent/metastatic squamous cell carcinoma of head and neck receiving gemcitabine plus cisplatin treatment: report of a multi-center phase II study.

PURPOSE: The efficacy and safety of gemcitabine in combination with cisplatin (GC) as the first-line treatment in patients with recurrent/metastatic (R/M) squamous cell carcinoma of head and neck (SCCHN) was examined. PATIENTS AND METHODS: Patients with R/M SCCHN without prior treatment for their R/M disease were eligible and treated with gemcitabine 1,250 mg/m(2) on day 1, day 8 and cisplatin 80 mg/m(2) on day 8 every 21 days. RESULTS: Forty patients were enrolled from March 2004 to January 2006, and 30 were evaluable for treatment effectiveness and outcome. The median age of evaluable patients was 50 years and all patients were male. Partial response was observed in 9 (30%) and stable disease in 7 (23.3%) patients. The overall response rate and disease control rate was 30 and 53.3%, respectively. The major toxic effects were ≥grade 3 leukopenia and anemia (65 and 27.5%, respectively). With a follow-up of 72 months, the median time to progression (TTP) was 128 days (95% CI, 78-242) and median overall survival (OS) was 401 days (95% CI, 216 approximately not reached). CONCLUSIONS: This GC regimen demonstrates a good activity and a promising survival period in patients with R/M SCCHN.

Role of ATP in the ROS-mediated laryngeal airway hyperreactivity induced by laryngeal acid-pepsin insult in anesthetized rats.

The pathogenetic mechanisms of laryngeal airway hyperreactivity (LAH) in patients with extraesophageal reflux are unclear. We recently reported that a laryngeal acid-pepsin insult produces LAH that is mediated through sensitization of the capsaicin-sensitive laryngeal afferent fibers by reactive oxygen species (ROS) in rats. Since ROS may promote the release of ATP from cells, we hypothesized that activation of P2X purinoceptors by ATP subsequent to an increase in ROS induces LAH in an inflamed larynx that has been insulted by acid-pepsin or H(2)O(2) (a major type of ROS). The larynxes of 208 anesthetized rats were functionally isolated while the animals breathed spontaneously. Ammonia vapor was delivered into the larynx to measure laryngeal reflex reactivity. Laryngeal insult with acid-pepsin or H(2)O(2) produced LAH with similar characteristics. The H(2)O(2)-induced LAH was prevented by laryngeal pretreatment with dimethylthiourea (a hydroxyl radical scavenger), suggesting a critical role for ROS. The LAH induced by both insults were completely prevented by ATP scavengers (a combination of apyrase and adenosine deaminase) or a P2X receptor antagonist (iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate). Laryngeal application of a P2X receptor agonist (alpha,beta-methylene-ATP) also produced LAH. An insult with either acid-pepsin or H(2)O(2) similarly promoted an increase in the levels of ATP, lipid peroxidation, and inflammation in the larynx. Our findings suggest that laryngeal insult with acid-pepsin or H(2)O(2) induces inflammation and produces excess ROS in the rat's larynx. The latter may in turn promote the release of ATP to activate P2X receptors, resulting in sensitization of capsaicin-sensitive laryngeal afferent fibers and LAH.

Positron emission tomography in surveillance of head and neck squamous cell carcinoma after definitive chemoradiotherapy.

BACKGROUND: We assessed the role of (18)F-fluoro-deoxy-glucose positron emission tomography (PET) in detecting head and neck squamous cell carcinoma (HNSCC) after definitive chemoradiotherapy (CRT). METHODS: A prospective study presented 80 PET before and after CRT for 44 patients, including 44 first-time post-CRT scans performed between 12 and 17 weeks after radiotherapy completion, as well as 10 repeated scans in the subsequent follow-up. PET interpretations were compared with clinicopathologic outcomes. RESULTS: PET demonstrated better performance than CT in post-CRT surveillance. Considering all 54 post-CRT PET scans, sensitivity for detecting primary tumors was 100%, specificity 93%, positive predictive value (PPV) 80%, and negative predictive value (NPV) 100%. For cervical diseases, sensitivity was 100%, specificity 98%, PPV 92%, and NPV 100%. For distant metastases, sensitivity was 100%, specificity 98%, PPV 86%, and NPV 100%. CONCLUSIONS: Negative PET readings were reliable for predicting free of HNSCC and helpful for selected patients in post-CRT surveillance.

Role of chest computed tomography in head and neck cancer.

OBJECTIVES: To evaluate the role of chest computed tomography (CT) in patients with head and neck squamous cell carcinoma (HNSCC) and to determine the optimal timing and predictive factors for positive findings. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Two hundred seventy screening chest CT scans performed in 192 patients with HNSCC during a 42-month period were reviewed. MAIN OUTCOME MEASURES: The scans were categorized as new cases, follow-up cases, or recurrent cases. The results were classified as abnormal or normal. Scans of patients having a radiologic diagnosis of a malignant neoplasm of the lung or an indeterminate lesion were considered abnormal. Factors correlating with an abnormal chest CT scan or development of malignant neoplasm of the lung were analyzed, including the timing of imaging and the patients' clinicopathologic data. RESULTS: Seventy-nine scans (29.3%) were considered abnormal. The rate of an abnormal scan was significantly higher in the follow-up case group (44.2%) than in the new case group (14.2%) (P < .001). Ten of 15 indeterminate scans (66.7%) with small (<1 cm) solitary pulmonary nodules showed disease progression on subsequent follow-up scans, changing the patients' diagnoses to a malignant neoplasm of the lung. The predictive factors for development of a malignant neoplasm of the lung were initial N2 or N3 disease, stage IV disease, recurrent disease, and distant metastasis to another site. CONCLUSIONS: Chest CT is recommended for high-risk patients, especially during the follow-up period. Intensified evaluation and management are mandatory for indeterminate small solitary pulmonary nodules because of the high rate of malignant neoplasms.

Chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer.

OBJECTIVE: Laryngeal preservation is a challenge for the treatment of advanced hypopharyngeal cancer. The objective of this study is to evaluate the results of chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer at a single institute and the impact of treatment factors on prognosis. METHODS: The study population consisted of 42 consecutive patients with resectable stage III-IV hypopharyngeal cancer. Patients with T4b tumor, synchronous primary cancer or those treated palliatively were excluded. Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) was performed in 32 (76.2%) patients, whereas primary CCRT was done in the other 10 (23.8%). Patients were grouped according to the dose intensity of chemotherapy and total dose of radiotherapy (RT). RESULTS: Grade 3-4 toxicities occurred mostly during CCRT. Thirty-five (83.3%) patients received an optimum dose of cisplatin (CT-optimum), 27 (64.3%) received an optimum dose of RT-optimum and 26 (61.9%) received optimum doses of both (CRT-optimum). CT- and RT-optimum both correlated significantly with better disease-free survival (DFS) (P < 0.001 and = 0.003), overall survival (OS) (P < 0.001 and = 0.004) and laryngeal preservation survival (LPS) (P = 0.01 and 0.04). The 3-year DFS, OS and LPS for CRT-optimum patients were 48.1, 50.0 and 45.6%, respectively. CONCLUSIONS: Achievement of optimum treatment dose remains challenging in chemoradiotherapy laryngeal preservation for advanced hypopharyngeal cancer. Intensive patient care and monitoring by experienced multi-disciplinary teamwork are mandatory. The criteria for selecting patients who will respond to and complete the treatment remain key issues for future investigation.

Methotrexate and leucovorin double-modulated 5-fluorouracil combined with cisplatin (MPFL) in metastatic/recurrent head and neck cancer.

BACKGROUND: To determine the efficacy and safety profile of the combination of cisplatin and 5-fluorouracil modulated both by methotrexate and leucovorin in metastatic/recurrent squamous cell carcinoma of the head and neck. METHODS: Twenty-eight patients were treated with cisplatin 40 mg/m2/day continuous infusion for 24 hours on day 1; high-dose 5-fluorouracil 2,000 mg/m2/day and leucovorin 100 mg/m2/day continuous infusion for 48 hours on days 1 and 2; methotrexate 40 mg/m2/day as a bolus infusion 4 hours before 5-fluorouracil and leucovorin on day 1. The treatment was repeated every 2 weeks in a cycle. RESULTS: The overall response rate was 25%, and 14% of the patients achieved stable disease status. Subgroup analysis demonstrated significantly improved overall survival in the disease-control group (12.0 months vs. 5.3 months, p<0.001). Only 3 (10.7%) patients developed grade 3-4 neutropenia, and none developed grade 3-4 non-hematologic toxicity. CONCLUSION: This multiagent-containing regimen has an excellent safety profile and improved survival in disease-control group of patients with metastatic/recurrent squamous cell carcinoma of the head and neck.

Effectiveness of pharmacokinetic modulating chemotherapy combined with cisplatin as induction chemotherapy in resectable locally advanced head and neck cancer: phase II study.

PURPOSE: To test the efficacy and safety of pharmacokinetic modulating chemotherapy combined with cisplatin (PMC-cisplatin) as induction chemotherapy (ICT) before definitive treatment in patients with respectable locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Patients with stage III-IV resectable locally advanced HNSCC were enrolled. All eligible patients received PMC-cisplatin regimen as ICT containing intravenous leucovorin 250 mg/m(2) and 5-FU 600 mg/m(2) on day 1, oral tegafur-uracil (UFUR) 250 mg/m(2)/day on days 1-5, repeated every week for six courses. Cisplatin 100 mg/m(2 )was given during the first and fourth courses of PMC. For ICT responders, concurrent chemoradiotherapy (CRT) with cisplatin/tegafur-uracil/70 Gy radiotherapy was performed. Salvage surgery plus postoperative CRT was given to ICT non-responders. RESULTS: The overall response rate of PMC-cisplatin as ICT was 76%, including a complete remission rate of 23%. The overall organ preservation rate of the multimodality treatment was 75%, with 97% in ICT responders. At a median follow-up of 25 months, 47% of the patients were still alive and disease-free. The superiority of disease-free survival was demonstrated in ICT responders. The 3-year overall survival rate was 67%. The toxicity of treatment was acceptable. CONCLUSIONS: Application of PMC-cisplatin as the induction chemotherapy before definitive treatment provides a promising result in treatment response and survival of advanced HNSCC. This regimen is effective and safe, and further studies considering the combination of PMC with other chemotherapeutics such as taxanes to improve the clinical outcome of advanced HNSCC is warranted.