Established prognostic variables in N0 oral carcinoma.

OBJECTIVES: To examine the utility of established prognostic variables in patients with oral carcinoma and a clinically negative neck. STUDY DESIGN: Retrospective cohort study. METHODS: The distribution of occult metastases was assessed in 105 oral cancer patients with no clinical or radiological evidence of nodal disease. Predictors for nodal metastases, recurrence, and survival were examined. RESULTS: Occult neck metastases occurred in 34 percent of patients. Tumor thickness was the only independent predictor of occult metastases, with thin (5 mm) tumors having a 10 percent and 46 percent incidence of regional disease, respectively (P = 0.001). Nodal metastases and perineural invasion were significant predictors of survival. CONCLUSION: Patients with thick tumors are at high risk of nodal metastases and are likely to benefit from elective neck dissection. Comprehensive neck dissection should be considered in advanced primary disease. SIGNIFICANCE: Tumor thickness is the most important predictor of occult regional metastases in oral cavity cancer.     

Locally invasive,well-differentiated thyroid cancer: 22 Years' experience at Memorial Sloan-Kettering Cancer Center

Our experience with 32 cases of locally invasive well-differentiated thyroid carcinoma suggests the following: (1) Thyroidectomy may be limited to the area of gross tumor involvement with little risk of recurrence in the normal opposite lobe. (2) Elective neck dissection should be considered in patients with locally invasive tumors since the incidence of nodal metastases is high. As observed in this study, occult metastases were present in five of six patients dissected electively, and nodal metastases developed later in four of eight patients observed. (3) Surgical procedures for the primary tumor should remove all gross disease. This is possible with conservative operations in most patients; the only deaths from uncontrolled local disease occurred in two patients in whom gross disease was left at the first procedure. Most deaths were caused by distant metastases, and the 5, 10 and 15 year survival rates were 86, 64 and 64 percent, respectively.     

Carcinoma of the lung: results of treatment over ten years.

Mediastinal lymph node dissection in conjunction with pulmonary resection was performed on 437 patients with bronchogenic carcinoma at the University of Michigan Medical Center from 1959 to 1969. The absolute five- and ten-year survival rates for patients undergoing curative resection were 36.2 and 14.4%, respectively. The five-year survival of those without nodal metastases was 49.3%, and it was 31.1% in patients with hilar metastases only. The five-year survival of patients with mediastinal metastases who received radiation therapy was 23.1%. Of the 193 patients with squamous cell carcinoma, 43% lived five years free from disease. The five-year survival of patients undergoing resection who had no hilar lymph node metastases was 53%, and it was 47.5% in those with hilar metastases only. The five-year survival in patients with mediastinal metastases who received postoperative irradiation was 34.4%.     

Metastatic cutaneous squamous cell carcinoma of the scalp

Background: Metastatic cutaneous squamous cell carcinoma arising from the scalp, although relatively uncommon, is associated with a poor outcome. Older men with a history of baldness and actinic scalp lesions are particularly at risk. Methods: Between 1980 and 2005, 27 patients with metastatic cutaneous squamous cell carcinoma of the scalp were referred to the Head and Neck Cancer Service at Westmead Hospital, Sydney. Relevant data were extracted from a prospectively maintained database. Patterns of recurrence and outcome were analysed. Results: Median age at diagnosis was 70 years and median follow up was 45 months in 26 men and one woman. Ten primary (index) lesions were located on the midline scalp, 14 left sided and 3 right sided. Median lesion size was 18 mm and median thickness was 5.5 mm. The median time between treatment of the scalp primary and the development of nodal metastases was 8 months. In 10 patients, nodal metastases were present at the time of primary treatment. Fifteen patients developed parotid metastases (+cervical nodes in 7 of 15) and 12 developed cervical only metastases (5 of 12 level V). All patients underwent nodal surgery and most (75%) also received adjuvant radiotherapy. At the last follow up, 41% of patients had died from their disease. Median survival after relapse was 9 months and all patients experiencing relapse died with most (11 of 13) dying from metastatic disease. Conclusion: Patients with metastatic cutaneous squamous cell carcinoma of the scalp have a poor prognosis with most dying from regional relapse. Those treated with surgery and adjuvant radiotherapy had a better outcome.     

Occult cervical metastases: immunoperoxidase analysis of the pathologically negative neck.

OBJECTIVES: The purpose of this study is to better estimate the true incidence of occult regional metastases associated with stage I and II squamous cell carcinoma of the oral cavity. The clinical and prognostic significance of micrometastatic disease discovered by cytokeratin immunoperoxidase reactivity in the previously pathologically N0 neck is also evaluated. METHODS: Forty patients treated between 1985 and 1996 with T1 or T2 squamous cell carcinoma of the lip and oral cavity were studied. All had primary surgical treatment including functional neck dissection. No metastases were demonstrated on hematoxylin and eosin microscopy. All specimens were reexamined with immunoperoxidase staining for cytokeratin. RESULTS: Five percent of patients had micrometastatic disease. Retrospective analysis of patients with a minimum follow-up of 2 years has failed to show a statistically significant association between a positive cytokeratin analysis and poor locoregional control or overall survival. CONCLUSIONS: Results suggest that the true incidence of occult metastases with carcinoma of the oral cavity is significantly higher than previously documented. However, the prognostic significance of these findings remains unclear.     

Prognostic value of initial mononucleated cell percentages in patients with epidermoid carcinoma of the head and neck

It has been established that staging of squamous cell carcinoma of the head and neck at the time of diagnosis carries the most significant prognostic factor. Searching for other prognostic factors at the time of diagnosis, the percentages of lymphocytes and monocytes in the peripheral blood were studied. The results revealed that there were significantly higher lymphocyte values in patients without regional lymph node metastasis compared with those with such metastasis (p = 0.0064). On the other hand, higher monocyte values correlated with advanced stages of the disease. Patients with regional lymph node metastasis had higher monocyte values than those without nodal metastases. Furthermore, the incidence of recurrences and metastases during the first year was significantly lower in patients who had lymphocyte values of 30 percent or more when compared with those with values of less than 30 percent (p = 0.0003). In addition, all patients with early stages (I and II) of disease had less than 10 percent monocytes. These data suggest that initial high lymphocyte and low monocyte percentages carry a better prognosis. It seems that the percentage of mononucleated cells in the peripheral blood may have the second most important prognostic value.     

Critical assessment of supraomohyoid neck dissection

During a recent 5-year period, 115 patients had 131 supraomohyoid neck dissections. Eighty-one percent of these procedures were performed for squamous carcinoma. Seventy-nine percent of the primary tumors were located in the oral cavity and 16 percent arose in the oropharynx. Almost 80 percent of the necks dissected for primary squamous carcinoma were clinically N0, and occult nodal disease was discovered in 31 percent of these neck specimens. When the supraomohyoid neck dissection specimen showed no involvement, the overall incidence of treatment failure in the neck at 2-year follow-up was 5 percent. Almost all patients with occult squamous carcinoma in the supraomohyoid neck dissection specimen received postoperative radiotherapy, and the failure rate in the neck was 15 percent. When neck nodes were both clinically and pathologically involved, neck recurrence developed in 29 percent of the patients despite the addition of adequate postoperative radiotherapy. Among those patients with nonsquamous primary tumors and a pathologically negative supraomohyoid neck dissection specimen, there was only one subsequent treatment failure in the neck. Supraomohyoid neck dissection appears to be a valid staging procedure for clinically N0 patients with primary squamous carcinomas located in the oral cavity or oropharynx, with an appropriate yield of occult nodal disease, and infrequent treatment failure in the dissected neck when the supraomohyoid neck dissection specimen is pathologically uninvolved. When nodal disease is clinically obvious, treatment failure is more frequent, even with the addition of postoperative radiotherapy. The role of supraomohyoid neck dissection in this setting deserves further study.     

The role of lymphadenectomy in penile cancer

In patients with squamous carcinoma of the penis, the presence and extent of metastases involving the inguinal nodes are the most important factors predictive of survival. Favorable prognostic indicators of cure in surgically treated patients in whom metastases develop include: (1) minimal nodal disease, (2) unilateral involvement, (3) no evidence of extranodal extension of cancer, and (4) absence of pelvic nodal metastases. Prophylactic lymphadenectomy in select patients at high risk for metastasis seems reasonable in lieu of prospective randomized trials because novel procedures have significantly decreased the morbidity of surgical staging. Patients with poor prognostic indicators either before or after surgery should be considered for multimodal therapy.     

Skip mediastinal nodal metastases in non-small cell lung cancer

Objective: To reveal the incidence and clinical significance of mediastinal nodal metastases without N1-station nodal metastases (‘skip-N2 metastases’) in non-small cell lung cancer (NSCLC). Methods: A total of 450 NSCLC patients who underwent tumor resection with a systemic mediastinal nodal dissection were retrospectively reviewed. p53 status and proliferative activity represented as proliferative index (PI) were also examined immunohistochemically. Results: Skip-N2 metastases were documented in 49 (13%) patients of all 450 patients; among 334 patients without N1-nodal involvement, 18% patients had skip-N2 metastases. The postoperative survival of skip-N2 patients was almost same as that for patients with metastases to both N1 and N2 nodes. Skip-N2 metastases were significantly more frequent in male patients and squamous cell carcinoma patients. In addition, the mean PI for tumor with skip-N2 metastases was significantly higher than that for any other pathologic nodal (pN)-status diseases. Combined with histologic type and PI, the incidences of skip-N2 metastases for adenocarcinoma showing lower PI were only 5% (7/137) of all patients and 7% (7/94) of patients without N1-nodal involvement. Conclusions: N1 nodal status is not a useful predictor of N2 nodal status in NSCLC, because skip-N2 metastases were documented in 18% patients showing no N1-nodal involvement. However, N1 node-guided dissection might be performed in patients with adenocarcinoma showing lower PI, because the incidence of skip-N2 metastases was extremely low.     

Meetings in North Americe,April–September, 1976

The results of major pulmonary resection in 58 patients greater than 70 years of age were reviewed. The histological distribution and extent of nodal metastases in this age group are the same as in younger patients. The absolute five-year survival rate for the 55 patients undergoing curative resection was 30% (17 patients). It was 36% (11 patients) for those patients with squamous cell carcinoma and 22% (5 patients) for those with adenocarcinoma. The operative mortality was only 14% (8 patients). Of the 49 patients treated by lobectomy, 17 lived five years or more free of disease, whereas none of the 6 patients treated by pneumonectomy survived five years.The five-year survival rate of 30% in this series of elderly patients treated by major pulmonary resection makes resections in such patients with bronchogenic carcinoma worthwhile.     

Three-field lymph node dissection for squamous cell and adenocarcinoma of the esophagus

OBJECTIVE: To determine the prevalence of occult cervical nodal metastases in patients with squamous cell cancer and adenocarcinoma of the esophagus, and to determine the impact of esophagectomy with three-field lymph node dissection on survival and recurrence rates. SUMMARY BACKGROUND DATA: Although esophagectomy with three-field lymph node dissection is commonly practiced in Japan, its role in the surgical management of esophageal cancer in the United States, especially in patients with esophageal adenocarcinoma, is essentially unknown. METHODS: This is a prospective observational study of esophagectomy with three-field lymphadenectomy. Eighty patients underwent resection between August 1994 and April 2001. Clinicopathological information and follow-up data were collected on all patients until death or June 2001. RESULTS: Hospital mortality and morbidity rates were 5% and 46%, respectively. Metastases to the recurrent laryngeal and/or deep cervical nodes occurred in 36% of patients irrespective of cell type (adenocarcinoma 37%, squamous 34%) or location within the esophagus (lower third 32%, middle third 60%). Overall 5-year and disease-free survival rates were 51% and 46%, respectively. Sixty-nine percent presented with nodal metastases. The 5-year survival rate for node-negative patients was 88%; that for those with nodal metastases was 33%. The 5-year survival rate in patients with positive cervical nodes was 25% (squamous 40%, adenocarcinoma 15%). CONCLUSIONS: Esophagectomy with three-field lymph node dissection can be performed with a low mortality and reasonable morbidity. Unsuspected metastases to the recurrent laryngeal and/or cervical nodes are present in 36% of patients regardless of cell type or location within the esophagus. Thirty percent of patients were upstaged, mainly from stage III to stage IV. An overall 5-year survival rate of 51% suggests a true survival benefit beyond that achieved solely on the basis of stage migration.     

Immunoexpression of p53 protein and proliferating cell nuclear antigen in penile carcinoma.

PURPOSE: We examined p53 protein and proliferating cell nuclear antigen immunoexpression as prognostic factors to the outcome of squamous cell carcinoma of the penis in 50 patients. MATERIALS AND METHODS: Penectomy and lymphadenectomy were performed in 14 patients with clinically positive nodes while 36 with cN0 disease were treated with penectomy and kept under surveillance that resulted in subsequent lymphadenectomy due to nodal relapse in 8. Of 21 patients with confirmed nodal metastases 18 died of disease. Immunohistochemical reactions were performed via the avidin-biotin-immunoperoxidase method and the results were compared with tumor pT stage, grade, nodal status and cause specific death. RESULTS: In univariate analysis proliferating cell nuclear antigen staining showed association only with nodal metastasis (p = 0.04) while p53 staining exhibited correlation with tumor pT stage (p = 0.0005), grade (p = 0.02), lymphatic spread (p = 0.02) and cause specific survival (p = 0.003). Multivariate analysis showed that p53 immunoreactivity was the only factor with prognostic significance for disease progression and cause specific survival. Tumor pT stage, grade and proliferating cell nuclear antigen staining had no significance for nodal metastases and cause specific death. CONCLUSIONS: Proliferating cell nuclear antigen staining had no prognostic value for disease progression. Since p53 over expression was associated with tumor progression and cause specific death, perhaps it should be evaluated in staging and therapeutic planning for patients with squamous cell carcinoma of the penis.     

The incidence of occult metastases for cancer of the oral tongue and floor of the mouth: Treatment rationale

One hundred thirty-six surgical cases of squamous cell carcinoma of the oral tongue and floor of the mouth at the Emory University Hospitals were reviewed for the incidence of occult metastases. Thirty-five percent of the T1 T2 lesions of the anterior tongue had occult metastases. The figure was 31.5% for similarly staged lesions of the floor of the mouth. The presence of regional metastases resulted in a 2-year determinate survival rate of 37% and 32% for patients with oral tongue and floor of the mouth lesions, respectively. The poor prognosis in the study for delayed cervical metastases and the high incidence of occult cervical metastases have led the authors to propose a more aggressive therapy for the clinically negative necks in these two sites of squamous cell carcinoma of the oral cavity.     

Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection

OBJECTIVE: To evaluate the long-term outcome of aggressive surgery incorporating hepatic resection and systematic nodal dissection for advanced carcinoma involving the hepatic hilus. SUMMARY BACKGROUND DATA: Few long-term results are available regarding radical surgery incorporating major hepatectomy and nodal dissection. METHODS: A retrospective analysis was undertaken in 107 patients with carcinoma involving the hepatic hilus treated between 1980 and 1997. Resectional surgery was performed in 65 patients, 52 of whom underwent major hepatectomies. The effects of clinical and pathologic factors were assessed by univariate and multivariate analyses. RESULTS: Sixty percent of the patients with resectional surgery had stage IVA or IVB disease, and 92.3% of them underwent major hepatectomies. No in-hospital deaths were encountered in the 35 most recent resections, whereas there were six deaths in the early period. Resectional surgery was associated with a survival benefit, especially when resection margins were free from cancerous infiltration. The estimated 5-year survival rate after resection, including all deaths, was 34.8%; this was 51.6% when the margins were clear. Nodal involvement was documented in 44.6% of the resections. However, patients with metastases limited to the regional nodes showed a survival rate similar to that in patients without nodal involvement. Significant predictive factors for survival after resection were extension to the gallbladder, nodal status, resectional margins, histologic type, and gender. CONCLUSIONS: The combination of major hepatectomy with systematic nodal dissection gave a good chance of prolonged survival for patients with carcinoma involving the hepatic hilus, even when the disease was advanced. Less-extensive procedures were also beneficial for less-advanced disease if clear resectional margins were secured.     

Carcinoma of the lung in patients under 40 years of age

Bronchogenic carcinoma in the young population (40 years of age or less) is reported to present in an advanced stage and to have a virulent course. Between 1969 and 1979, 101 patients (65 men and 36 women) presented with cancer of the lung. Their mean age was 36.2 +/- 3.9 years (range 18 to 40 years). Eighty-seven percent had a history of cigarette smoking. Fifty percent of the patients had a strong familial history of malignancy of several organs. The interval between onset of symptoms and diagnosis was 4.01 +/- 3.48 months (3.56 +/- 3.34 for the surgically treated group and 4.16 +/- 3.53 for the nonoperated or unresectable group). Diagnosis was made at bronchoscopy in 32 patients, during thoracotomy in 30 patients, during nodal biopsy in 28 patients, and on cytologic examination of the sputum in 9 patients. The most common cell types were adenocarcinoma in 39 patients, squamous carcinoma in 29 patients, and oat cell carcinoma in 18 patients. Eighty-six patients (the majority) presented in stage III, whereas 9 were in stage I and 6 were in stage II. Twenty-seven patients (26.7 percent) underwent resection for cure, whereas 18 patients were inoperable at surgery. Eighteen of the surgical patients had adjuvant radiotherapy, and chemotherapy, immunotherapy, or both. The average length of survival for the nonresected patients was 7.12 +/- 5.9 months (range 1 to 36 months) and the actuarial survival was 1.5 percent at 36 months. The survival for the surgically managed patients was 56.1 +/- 52.6 months (range 3 to 168 months) or 48 percent at 36 months. At 46 to 168 months after treatment, the only survivors were 13 patients who were surgically managed. Stage III patients had longer survival after surgery (24.1 +/- 24.6 months to 7.09 +/- 5.90 months; range 3 to 74 months and 1 to 36 months, respectively). The survival at 5 years for patients with stage I disease was 78.8 percent, stage II disease 66.6 percent, and stage III disease, 3.6 percent. Early diagnosis and aggressive surgical management are necessary to improve the survival of patients with bronchogenic carcinoma under 40 years of age.     

Transcapsular spread of metastatic squamous cell carcinoma from cervical lymph nodes

The incidence, extent, and selected clinicopathologic correlations of transcapsular spread from metastatic tumor in the cervical lymph nodes have been investigated in 210 specimens obtained by radical neck dissection from 203 patients with squamous cell carcinomas of the head and neck. Transcapsular spread was detected in 137 of 159 (86 percent) positive specimens, and classified as macroscopic in 74 (54 percent) and microscopic in 63 (46 percent). Macroscopic transcapsular spread was seen most frequently in association with large nodal masses more than 3 cm in diameter (48 of 70 specimens, 69 percent), but also occurred in some specimens with smaller lymph nodes less than 3 cm in diameter (26 of 67 specimens, 39 percent). Anatomic structures most commonly invaded in areas of neck dissection with macroscopic spread from nodal metastases were skeletal muscle (39 dissections) and the adventitial coat of the internal jugular vein (27 dissections). Macroscopic transcapsular infiltration was associated with a high incidence (44 percent) of recurrent tumor in the ipsilateral neck, particularly within 12 months of surgery. Microscopic transcapsular growth was associated with a lower incidence (25 percent) of recurrent tumor in the ipsilateral neck but the difference did not reach statistical significance. Similar recurrence figures (32 percent) were found in the minority of patients whose nodal disease was intracapsular at the time of neck dissection. More precise definition of the morphologic extent of transcapsular spread could be important in clarifying its clinicopathologic correlations.     

Clinical and pathologic prognostic variables in oropharyngeal squamous cell carcinoma

Eighty-five patients with squamous cell carcinoma of the oropharynx were studied to assess the value of histopathologic parameters related to their survival. The overall survival was 58 percent at 3 years and 51 percent at 5 years. Stepwise logistic regression analysis was used to determine the prognostic value of each of the histopathologic features. The extent of in situ carcinoma and presence of multifocality were positive predictors of survival, and perineural invasion and nodal involvement on clinical examination were negative predictors. None of the other parameters used in this study attained statistical significance. We conclude that the histologic grade traditionally used to predict clinical behavior may not be useful. Clinical stage, particularly nodal status; perineural invasion; and the multifocal or in situ disease, should be considered in pathologic reports to provide better prognostic profile in oropharyngeal carcinoma.     

Surgical management of squamous cell carcinoma of the floor of the mouth

Treatment failure and survival in 209 patients with squamous cell carcinoma of the floor of the mouth treated with surgery as the single curative modality are reported. Fifty percent of the patients had stage III and IV disease. The primary tumor was excised with 1 to 2 cm margins and the mandible was resected in 73 percent of the patients; 77 percent underwent radical neck dissection. No cures were observed in 11 patients with involved surgical margins on permanent section. For 198 patients with uninvolved margins, determinate survival at 5 years for all stages was 49 percent and 69, 64, 46, and 26 percent for stages I through IV (p less than 0.01). The most common sites of initial and ultimate treatment failure were the neck (42 of 72 patients) and distant metastases (33 of 53 patients), respectively. Treatment of the neck is identified as an unresolved problem in the management of early stage disease. Recent improvements in survival for stage III and IV disease are accounted for, in part, by adequate surgical resection.     

Long-term experience with childhood thyroid carcinoma.

Twenty patients with well-differentiated thyroid carcinoma, 20 yr of age or younger have been treated at Vanderbilt University Hospital. The young patient with thyroid carcinoma frequently presents with far-advanced disease but enjoys an improved survival. Preoperative scintiscanning is useful in the evaluation of patients with childhood thyroid carcinoma. A new noninvasive scan is described and appears to be promising in the preoperative differentiation between benign and malignant thyroid lesions in children and young adults. There is a high instance of nodal metastases, but long-term follow-up would indicate that lobectomy and modified neck dissection are sufficient for most patients. However, total thyroidectomy can be performed safely in those patients with disease in both lobes. Additionalally, frozen section diagnoses were found to be helpful in diagnosing and staging thyroid carcinoma.     

Cervical lymph node metastasis after local excision of early squamous cell carcinoma of the oral cavity

A total of 54 patients with stage I and stage II squamous cell carcinoma of the oral cavity were reviewed as to treatment modality, adequacy of treatment, and site of failure. Surgery was employed as the sole initial treatment modality in 52 patients. Forty-three underwent primary tumor excision alone and 9 underwent elective neck dissection at the time of primary tumor excision. The patients who underwent elective neck dissection at the time of excision of the primary tumor had a 3 year survival rate of 88 percent, in comparison to a survival rate of 77 percent in those patients whose initial therapy was directed solely at the primary tumor. A low incidence of local recurrence (2 percent) and a high incidence of neck recurrence (42 percent) were documented in those patients treated by primary tumor excision alone. Patients who underwent salvage neck dissection for recurrent neck node metastases had a 3 year survival rate of 56 percent. This study has documented a high incidence of cervical node recurrence in patients with T1 and T2 squamous cell carcinomas of the oral cavity treated by primary tumor excision alone and a poor survival rate after salvage therapy. A small group of patients who underwent elective neck dissection had a demonstrably high survival rate. These observations lend support to the call for elective neck dissection in patients with stage I and II oral cavity carcinoma but are not conclusive. Therapeutic decisions regarding elective treatment of the neck will continue to be made according to the best judgment and prejudices of the individual surgeon until a prospective, randomized multi-institutional study addressing this specific issue is undertaken.