A multifactorial analysis of melanoma. IV. Prognostic factors in 200 melanoma patients with distant metastases (stage III).

A multifactorial analysis of 200 cutaneous melanoma patients with distant metastasis (stage III) was performed on 13 clinical and pathological factors using the Cox regression analysis. There were only three dominant prognostic variables that independently predicted the patient's clinical course: (1) number of metastatic sites (1 vs. 2 vs. greater than or equal to 3, p less than 0.00001), (2) remission duration (less than 12 mo vs. greater than or equal to 12 mo, p = 0.0186), and (3) the location of the metastases (visceral vs. nonvisceral vs. combined, p = 0.0192). Factors that were not significant in the multifactorial analysis included the patients' age and sex, the site of the primary melanoma, the sequence of metastases, and all histopathological features of the primary melanoma (thickness, level of invasion, ulceration, growth pattern, pigmentation, and lymphocyte infiltration). For a single metastatic site, the 1-yr survival rate was 36%, while it was only 13% for 2 sites, and 0% for greater than or equal to 3 sites (p less than 0.00001). The 1-yr survival for patients was 40% for nonvisceral sites (skin, subcutaneous, distant lymph nodes) compared to only 11% for visceral metastases and 8% for combined sites (p less than 0.00001). Pulmonary metastases were associated with a significantly higher survival rate than metastatic melanoma in any other visceral site. The most common first site of distant metastases (either alone or in combination) was skin (38%), lung (36%), liver (20%), and brain (20%). The skin, subcutaneous and distant lymph node group was the first site of metastases in 59% of patients. This finding emphasizes the importance of careful physical exams in routine metastatic evaluations. Only a minority (25%) of stage I patients progressed to stage III disease after a median interval of 2.8 years. In contrast, the majority (75%) of melanoma patients with nodal metastases (stage II) progressed to stage III disease after a median duration of only 11 mo. Of the patients who eventually developed stage III disease, 95% of those who initially presented with stage II disease progressed within 3 yr, while stage I patients who progressed to stage III did not reach a 95% cumulative incidence until 8 yr.

Cystic epithelial-stromal tumor of the seminal vesicle.

A cystic tumor composed of atypical glands in a cellular stroma arose in the pelvis of a 49-year-old man. Two years later an identical tumor was again excised from the pelvis. Morphologic, immunohistochemical and ultrastructural studies indicate that this neoplasm arose in the seminal vesicle, possibly from a seminal vesicle cyst. The tumor did not involve the prostate gland, and immunohistochemical stains for prostate-specific antigen and prostatic acid phosphatase were negative. Ultrastructural study showed that both the glandular and mesenchymal components of the tumor recapitulated features of normal seminal vesicle, further establishing origin from this site. This tumor resembles the rare cystadenoma of the seminal vesicle, yet the cytologic atypia suggests low grade malignant potential. Following the second excision, the patient has had a disease-free interval of 18 months. Long term follow-up and recognition of additional cases is necessary to define the biologic potential of this unusual tumor.

A multifactorial analysis of melanoma. II. Prognostic factors in patients with stage I (localized) melanoma.

Stage I melanoma encompasses an extraordinary diversity of biologic behavior. In such a setting where numerous parameters appear to influence survival, a multifactorial analysis using Cox's regression model is a valuable statistical model. Using a computerized data base of 394 clinical stage I melanoma patients treated at this institution during the past 20 years, a multifactorial analysis was used to compare the relative prognostic strength of 11 parameters. Two pathological factors (tumor thickness and ulceration) and two clinial factors (initial surgical treatment and anatomic location) were identified as the dominant prognostic variables. Other factors examined simultaneously that did not provide additional predictive influence on survival included the level of invasion, pigmentation, growth pattern, lymphocyte infiltration, pathological state, sex, and age. Melanoma thickness was the most important factor for predicting survival in patients with stage I melanoma (P less than 10(-8). This parameter is easy to measure and provides a quantitative estimate of clinically occult regional and distant metastases. Contrary to other reports using single factor analysis, the type of initial surgical treatment, in fact, did influence survival after other variables were taken into consideration. Thus the multifactorial analysis supports the observation that patients with intermediate thickness melanoma thickness of 1.5 to 3.99 mm had a 78% 8-year survival rate with wide excision of the melanoma and elective node dissection, while none survived more than 8 years if a melanoma of the same thickness was only widely excised. Multifactorial analysis is a useful and important statistical method when comparing treatment alternatives and prognostic factors in patients with melanoma.

Total pharyngeal reconstruction using a pectoralis major myocutaneous tunnel.

Total pharyngeal reconstruction was performed using a pectoralis major myocutaneous flap. In this technique, the posterior wall of the neopharynx consists only of the prevertebral tissue, while the flap forms the anterior and lateral walls. The posterior wall heals by reepithelialization of the prevertebral fascia. Clinical experience with seven patients has shown that this technique provides a wide conduit and is not prone to develop stenosis.

Paragangliomas of the neck.

Between 1967 and 1990 inclusive, 28 patients with paragangliomas of the neck were diagnosed at the University of Alabama at Birmingham Affiliated Hospitals. There were 11 men and 17 women, whose ages ranged from 12 to 76 years (mean, 47 years). Tumor locations included the carotid bodies (19 cases), the vagus nerves (three), supraglottic larynx (two), the left lateral pharyngeal wall (one), posterior to the right jugular vein (not otherwise defined) (one), subcutaneous neck tissue (one), and a cervical lymph node with unknown primary (one). Diagnostic workup included angiography (23 cases) with preoperative embolization (three), computed tomography (one), magnetic resonance imaging (two), and urinary catecholamine assay (four). All 28 patients underwent resection of the lesions. Cranial nerve damage occurred in 11 patients (39%). There were no perioperative deaths or cerebrovascular accidents, although one of two saphenous vein grafts became thrombotic after carotid body tumor resection.

Does radical mastectomy still have a place in the treatment of primary operable breast cancer?

This study (Alabama Breast Cancer Project) reports the ten-year surgical results of a prospective randomized trial comparing Halsted radical mastectomy (RM) with modified radical mastectomy (MRM) for breast cancer. We entered 311 patients in the study between 1975 and 1978. Patients with histologically positive axillary lymph nodes were randomized after operation to receive melphalan or intermittent intravenous cyclophosphamide, methotrexate, and fluorouracil for one year. After a median follow-up of ten years, there was no significant difference in the survival of the two groups (RM, 71%; MRM, 64%). Local recurrence after RM was significantly lower than after MRM. A subset of patients with more advanced cancers (T3 and T2 with clinically positive axillary nodes) experienced significantly better survival at ten years following RM compared with MRM (59% vs 38%, respectively). These results indicate that overall survival is similar for patients treated by either RM or MRM. However, there is subset of patients with more advanced cancers whose ultimate survival can be favorably influenced by RM.

Pharyngoesophageal diverticulum complicated by squamous cell carcinoma.

Pharyngoesophageal (Zenker's) diverticulum is a relatively common acquired condition that may cause dysphagia and regurgitation of food. Squamous carcinoma may develop in such a diverticulum, but this complication is exceedingly rare and may not be suspected preoperatively. This report describes a case in which the diagnosis of squamous carcinoma was made after regurgitation of malignant tissue from a radiographically proven pharyngoesophageal diverticulum. The patient was treated by simple diverticulectomy and postoperative radiation therapy.

Malignant salivary tumors--analysis of prognostic factors and survival.

A group of 113 patients with malignant salivary gland tumors was retrospectively reviewed to analyze the association of clinical and histologic factors with survival. These factors were patient sex and age, tumor site, clinical stage, histologic diagnosis, tumor grade, and whether or not final surgical margins were clear. There were 57 parotid, 40 minor salivary, and 16 submandibular gland cancers. The histologic groups were mucoepidermoid carcinoma (49 patients), adenoid cystic carcinoma (31), adenocarcinoma not otherwise specified (18), acinic cell carcinoma (7), malignant mixed tumor (5), squamous cell carcinoma (2), and undifferentiated carcinoma (1). Univariate analysis of clinical factors showed that age and clinical stage significantly influenced survival. At 10 yr the predicted cumulative survival rates for Stage I, II, III, and IV tumors were 74%, 56%, 32%, and 10%, respectively. Tumor grade was the only significant histologic factor. This was most obviously reflected among patients with mucoepidermoid carcinomas. Cumulative survival at 5 yr was 94% for those with low-grade tumors and 26% for high-grade tumors. By multivariate analysis, clinical stage, age, and tumor grade remained highly significant. Analysis of patients with only Stage I and II disease demonstrated that the significant factors were patient age, tumor site, tumor grade, and whether or not surgical clearance was achieved. These results suggest that clinical stage should not be the exclusive determinant of the extent of surgery and that the selection of patients, for adjuvant therapy may be improved by an awareness of these prognostic factors.

Surgical treatment of early-stage carcinoma of the oral tongue--wound adjuvant treatment be beneficial?

A group of 97 patients with clinical stage I and stage II squamous carcinoma of the oral tongue, treated by partial glossectomy alone, has been reviewed to define prognostic indicators. Sixty-seven patients were staged T1N0 and 30 were T2N0. Disease recurred in 28 patients (27%) and the most common site of failure was the ipsilateral neck (21%). The incidence of initial recurrence did not vary significantly with patient age, sex, T-stage, or when tumor size was examined in other subdivisions. The presence of perineural invasion significantly increased recurrence rate (P = 0.003) and decreased survival (P = 0.002). Disease-free survival at 5 yr was 73% for patients with T1 tumors, and 62% for T2 tumors. This difference was not significant. In this low-risk patient population with early stage carcinoma of the oral tongue, partial glossectomy is adequate treatment in most cases. However, we recommend postoperative radiation therapy to the primary site and ipsilateral neck for patients with perineural invasion. No evidence could be found to support adjuvant local therapy or elective neck treatment in the remaining patients.

Hayes Martin lecture. Vicissitudes of head and neck cancer.

In this study 136 of 167 patients (81 percent) with squamous cell carcinoma of the anterior tongue had no clinically evident neck node metastases. In 92 patients who received no elective treatment to the neck, 8 percent had recurrences at the primary site and 25 percent had recurrences in the neck with the primary site controlled. Three factors identify those patients at highest risk for harboring occult metastases: clinical size of the primary tumor, the presence of perineural invasion, and the sex of the patient (men fare worse). Patients with primary tumors of 1 cm or less in greatest diameter should not have elective treatment to the at-risk neck, patients with tumors greater than 3 cm in greatest diameter should receive treatment to the at-risk neck, and patients with cancer demonstrating perineural invasion should receive treatment to the at-risk neck. In the future, randomized controlled trials evaluating the efficacy of elective treatment to the at-risk neck should include only those patients at intermediate risk for harboring occult neck node metastases (that is, primary tumors 1 to 3 cm in greatest dimension without perineural invasion). Careful retrospective multifactorial analysis of the natural history and prognosis should always precede prospective, randomized trials to prevent the randomization of patients whose outcome can be predetermined on the basis of clinical and histologic characteristics.

Modified radical neck dissection. Terminology, technique, and indications.

The terminology relating to the various modifications of radical neck dissection is loose and confusing. A simple system of nomenclature has been suggested which allows specification of the node levels dissected and the structures preserved. A technique of modified neck dissection, which excludes dissection of the posterior triangle and spares the sternocleidomastoid muscle and spinal accessory nerve, has been described. We believe this operation is appropriate when local disease is advanced and clinically uninvolved neck nodes are likely to harbor occult metastatic disease, when resection of the primary tumor is through the neck, or when clinical disease in the neck is minimal. Patients with multiple palpable nodes, patients with nodes larger than 3 cm in diameter, patients with disease in the posterior triangle, and patients in whom radiotherapy to the neck has failed may be better served by radical neck dissection.

Squamous cell carcinoma of the buccal mucosa: analysis of prognostic factors.

Although the TNM system is the accepted standard for head and neck tumor classification, there are often discrepancies between tumor size and survival. This retrospective analysis of 89 patients with squamous cell carcinoma of the buccal mucosa was carried out to evaluate tumor thickness and depth of invasion as prognostic variables and to compare them to the standard parameters. Recurrence rates increased with tumor size, clinical stage, thickness, and depth of invasion. In univariate analysis, sex, clinical stage, thickness, and depth of invasion were significantly related to survival (p less than 0.10). Multivariate analysis revealed that only thickness was an independent variable (p less than 0.0001). Patients with tumors less than 6 mm in thickness had a significantly better survival rate compared with those patients with tumors greater than 6 mm in thickness, regardless of the tumor stage. Measurement of tumor thickness should be included in estimating prognosis, planning therapy, and comparing results in patients with squamous cell carcinoma of the buccal mucosa.

Neck dissection with and without radiotherapy: prognostic factors, patterns of recurrence, and survival.

A group of 179 patients who had 205 neck dissections between 1979 and 1984 has been reviewed to assess the influence of adjuvant radiotherapy on survival. Lymph nodes were histologically involved in 91 of 107 radical neck dissections (85 percent) and 55 of 98 modified neck dissections (56 percent). Eighty-two patients received adjuvant radiotherapy of 5,000 rads or more. Patients with involved nodes had significantly lower survival rates than those with uninvolved nodes. Among patients with involved nodes, survival was significantly lower when two or more nodes were involved, when there was nodal involvement at multiple levels, or when extracapsular spread was present. Adjuvant radiotherapy was associated with a reduced recurrence rate in the ipsilateral neck but the incidence of distant metastases was higher. When patients with involved nodes were subgrouped according to prognostic factors, the survival of irradiated patients was improved only in the highest risk group, but this was not statistically significant. When radiotherapy is added to neck dissection for treatment of cervical metastases it can be expected to reduced ipsilateral neck recurrence and prevent relapse in the contralateral neck. Improved survival may depend on an ability to detect and treat occult distant metastases.

Histopathological prognostic factors of certain primary oral cavity cancers.

The TNM classification of cancers arising in the upper aerodigestive tract is a generally useful and widely applied method for estimating prognosis and planning therapy. In two retrospective reviews of patients with oral cavity cancers, we identified additional histopathological characteristics that were significantly related to treatment outcome. A study of 136 patients with squamous cell carcinoma of the anterior tongue (without clinical metastases) demonstrated, in a multifactorial analysis, three factors associated with a high risk of occult metastases: Clinical size of the primary tumor, presence of perineural invasion, and male gender. In a second analysis, of 89 patients with squamous cell carcinoma of the buccal mucosa, many pathologic and clinical parameters were related to prognosis using single-factor analysis. However, in multifactorial analysis only tumor thickness and vascular invasion were predictive of outcome.

Conventional TRAM flap versus free microsurgical TRAM flap for immediate breast reconstruction.

Immediate breast reconstruction using the transverse abdominal myocutaneous island (TRAM) flap was performed in 54 patients over the past 3 years at our institution. This represented approximately 59 percent of patients undergoing all types of immediate breast reconstruction. In 10 patients, the abdominal island flap was transferred as a free flap based on the deep inferior epigastric pedicle. These patients were compared with the other 44 patients, in whom the flap was transferred using the conventional technique. The TRAM flap is well suited for immediate breast reconstruction because the procedure can be carried out simultaneously with mastectomy using separate operating teams and instruments. The operation is safe and relatively free of complications. The free TRAM group compared favorably with the conventional group in terms of complications, operating time, estimated blood loss, hospitalization, and return to functional baseline. The free TRAM flap appears to be as safe as the conventional technique with the advantages of a more limited rectus muscle harvest, improved medial contour of the breast due to the lack of tunneling, and perhaps a healthier flap because of the large donor vessels.

The logic of adjunctive therapy in surgical patients with resectable cancer.

The principles and rationale of using multiple modalities (surgery, chemotherapy, radiotherapy, and immunotherapy) to treat solid malignancies is reviewed. Animal models of human tumors have clearly demonstrated the superiority of combining local treatment (eg, surgery) with systemic treatment (eg, chemotherapy). Although the results of many trials of adjunctive therapy in man are still preliminary, they warrant the caustious generalization that multiple modality therapy will increasingly become more effective than surgery alone for most types of solid tumors. Although the strategy of employing adjunctive therapy is rational, it must be emphasized that the therapeutic efficacy of specific drugs or agents for particular patients or tumor types has not always been satisfactory. Clinical trials now in progress may demonstrate more effective regimens. In the meantime, physicians should be cautious about using adjunctive therapy as standard treatment until long-term benefits and safety have been demonstrated. Participation in clinical trials is encouraged to verify the validity and application of this therapeutic approach.