Carcinosarcomas of the female genital tract. A pathologic study of 29 metastatic tumors: further evidence for the dominant role of the epithelial component and the conversion theory of histogenesis

Carcinosarcomas of the female genital tract have generally been regarded as a type of sarcoma. Recent evidence suggests, however, that they may be more closely related to carcinoma. The histologic features of 29 carcinosarcomas with documented metastases were analyzed to study the relative importance of the carcinomatous and sarcomatous components and attempt to provide further evidence on the histogenesis of these neoplasms. Patients' ages ranged from 33 to 81 years (mean, 68). The primary tumor originated in the uterus in 17 cases, the ovary in 11, and the fallopian tube in one. Heterologous sarcoma was present in 21 of the primary tumors (72%). Myometrial invasion was present in all 15 of the uterine tumors treated with hysterectomy and consisted only of the carcinomatous component in 12 cases (80%). In two cases, which possibly developed as "collision"-type carcinosarcomas, the myometrium was separately invaded by carcinoma and sarcoma. Myoinvasive tumor consisted solely of sarcoma in one case. Lymphatic-vascular invasion was found in 10 of the primary tumors (eight uterine, two extrauterine) and consisted of pure carcinoma in all instances. The cellular composition of 62 metastases was evaluated. Of these, 51 metastases were diagnosed concurrently with the primary tumor in 21 patients (73%). Eleven metastases were diagnosed from 2 to 26 months after initial treatment. Carcinoma only was found in 43 metastases (70%), both carcinoma and sarcoma in 15 (24%), and sarcoma alone in four (6%). A total of 35 lymph node metastases occurred in 10 cases, consisting of carcinoma alone at 34 sites. The sole example of a purely sarcomatous lymph node metastasis occurred in one of the possible uterine "collision"-type tumors. Intraperitoneal metastases to serosal surfaces or the omentum occurred in 19 cases and consisted of both carcinoma and sarcoma in 14 and carcinoma only in five. Vaginal metastases occurred in four cases and consisted of only carcinoma in two, carcinoma and sarcoma in one and only sarcoma in one. Four patients had distant organ metastases, including one each to the liver (carcinoma only), breast (carcinoma only), bone marrow (sarcoma only), and brain (sarcoma only). Of the 51 concurrent metastases, only carcinoma was present in 37 (73%), both carcinoma and sarcoma in 13 (26%), and sarcoma alone in one. Of the 11 subsequent metastases, carcinoma alone was found in six (55%), sarcoma alone in three (27%), and both carcinoma and sarcoma in two (18%).(ABSTRACT TRUNCATED AT 400 WORDS)     

A long-term assessment of adjuvant chemotherapy on outcome of patients with extracapsular spread of cervical metastases from squamous carcinoma of the head and neck

BACKGROUND: Extracapsular spread (ECS) of cervical lymph node metastases of squamous cell carcinoma from head and neck sites portend poor prognosis. Therefore, a program of combined surgery, postoperative irradiation therapy, and adjuvant methotrexate and 5-fluorouracil (5-FU) was initiated in 1982 for such patients. METHOD: All patients operated on between June 1982 and December 1992 by the full-time faculty of the Department of Otolaryngology at the University of Pittsburgh School of Medicine were eligible and reported in this trial. All patients had negative surgical margins of excision of the primary carcinoma, and histologic evidence of cervical metastases with ECS. Postoperative irradiation included 50-60 cGy for 5 to 6 weeks followed by methotrexate and 5-FU administered on an outpatient basis on days 1 and 8 every 21 days. All patients were followed for 30 or more months for evidence of recurrent disease. RESULT: A total of 371 patients met eligibility criteria. Of this group, 53 (14%) were treated with surgery only, 187 (50%) received surgery and postoperative irradiation, and 131 (35%) received surgery, irradiation therapy, and chemotherapy. The primary site, extent of nodal involvement, and stage of the three patient groups were similar. However, performance status (Karnofsky) was best in the patients who received chemoradiation (average 90) when compared with those who received surgery and irradiation (average 80) or surgery only (average 70). Absolute disease free survival rate (30 months) was 9.5% in patients treated with surgery only, 34% in patients treated with surgery plus irradiation, and 53% in patients treated with surgery, irradiation, and chemotherapy. When adjusted for patients who died of intercurrent disease with less than 30 months follow-up, survival rates became 17%, 40%, and 58%, respectively. These differences are highly significant (P < 0.001). CONCLUSION: Results of this study suggest that postoperative chemoradiation may improve survival in patients with ECS of cervical metastases. Compliance with the chemoradiation was suboptimal and suggests that improved strategy must be developed.     

Small-intestinal digestion of partially resistant cornstarch in healthy subjects

Primary adenocarcinoma of sweat glands is a rare tumor; approximately 220 cases have been reported in the last 30 years. We reviewed the charts of patients with primary diagnosis of this tumor treated at the Mayo Clinic between 1935 and 1995. We included only cases with initial histology slides available for re-examination. Tumors were classified into five recognizable histologic patterns (solid, ductal, mucinous, microcystic adnexal, and adenocystic carcinoma) and graded by the Broder system. Statistical analysis consisted of Kaplan-Meier product limit method and Cox multiple regression test. In total, 55 patients were identified, and age ranged from 13 to 85 years (mean 59 years). Thirty-six patients (65 percent) presented to the Mayo Clinic for initial treatment; all except one had disease limited to the primary site. Microcystic adnexal carcinoma was the most frequent type, and more than 50 percent were grade 2 tumors. Among these 36 patients, 4 had some type of recurrence. Patients who developed metastasis had a high-grade tumor in the initial biopsy. Nineteen patients were referred with recurrence; 13 had local recurrence, 4 had regional diseases, and 2 had distant metastases. The histologic distribution showed 47 percent solid tumors, and 37 percent of them were grade 3. Multiple regression analysis did not show a difference in recurrence or survival when gender, age, tumor location, or histologic pattern was evaluated. In addition, there was no difference in the outcome between wide surgical resection and micrographic surgery. The only predictive factor for distant metastases and/or death (p < 0.003) was histologic grade. Overall 10-year survival rate was 86 and 60 percent for primary and referred patients, respectively. We conclude that histologic diagnosis of sweat gland carcinoma must be complemented by clinical examination to evaluate metastases. Clinical behavior depends on the histologic type of tumor, degree of differentiation, and clinical stage. On recurrence, the likelihood of further recurrences and mortality increases dramatically. Aggressive initial local ablation with tumor-free margins is recommended. In high-grade tumors, prophylactic regional lymph node dissection may further characterize tumor aggressiveness and may justify adjuvant radiotherapy as part of the primary treatment.     

Pathologic correlates of prognosis in lymph node-positive breast carcinomas

BACKGROUND: Many pathologic features of breast carcinomas have been proposed as prognostic correlates; their interrelationships and their relative value as prognostic indicators were studied. METHODS: A series of 399 axillary lymph node-positive infiltrating ductal breast carcinomas was studied histologically and compared with the patient prognosis. RESULTS: Many pathologic findings fit into two groups of closely related features--those related to the extent of local spread and those related to histologic anaplasia and mitotic count. Both groups correlated with the primary tumor size. The best predictors of long-term survival were measures of the extent of axillary metastasis (the number of axillary metastases, the size of the largest metastasis, and lymph node capsular invasion), which are components of the pathologic node stage. The mitotic count, tumor grade, primary tumor stage, smooth tumor border, tumor necrosis, and multifocal primary tumors were weaker but significant survival correlates. The mitotic count and Bloom-Richardson grade best predicted the survival time of patients with node-positive disease who died. Four years after diagnosis, less than 25% of the patients who would die of breast carcinoma in the low mitotic count and Bloom-Richardson Grade 1 (well differentiated) groups already had died; more than 75% of those in the high mitotic count and Bloom-Richardson Grade 3 (poorly differentiated) groups already had died. Among patients with small tumors (< 1.8 cm in diameter), those with one micrometastasis (1-2 mm) had a worse prognosis than those with uninvolved lymph nodes of similar size. CONCLUSION: The extent of axillary metastasis best predicted the long-term prognosis of patients with infiltrating ductal carcinoma and axillary metastases. The mitotic count and tumor grade best predicted the survival time of those who died.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Surgical treatment of lung cancer with chest wall invasion

From January 1986 to May 1998, 45 lung cancer patients with chest wall invasion (P3) underwent resection (40 male, 5 female), (median age 63.2 yrs (30-79)). Histological types were squamous cell carcinoma in 20, adenocarcinoma in 14, large cell carcinoma in 7, adenosquamous cell carcinoma in 2, and unknown in 2. Operative methods of lung resection were total pneumonectomy in 2, bilobectomy in 3, lobectomy in 38, and partial lung resection in 2. Resection was regarded as complete in 35 and incomplete in 10 patients. Thirty one patients had negative lymph nodes (N0), 9 had peribronchial or hilar lymph node metastases (N1), and 5 had mediastinal lymph node metastases (N2). The extent of tumor invasion to chest wall was P3a (invasion within parietal pleura) in 11, P3b-c (invasion to intercostal muscle) in 16, P3d (invasion to rib) in 18, patients. 5-year survival rate was totally 19.7%. Cisplatin based chemotherapy and concurrent thoracic radiation following surgery (CCRT) was performed in latest nine P3d cases. Partial response was observed in 5 of 9 cases (response rate 56%) and viable tumor cell in the primary site was not seen histologically in 5 of 9 cases. Three year survival rate was 46.9% for CCRT(+) 11.1% for CCRT(-). Acturial 5-year survival rate in P3a-d was 19.76%. P3d cases had poor survival, but CCRT improved prognosis of P3d cases.     

Squamous cell carcinoma of the soft palate

Thirty-eight patients with squamous cell carcinoma of the soft palate treated between 1960 and 1975 were reviewed. Males in the seventh decade predominated. All symptomatic patients complained of sore throat and/or odynophagia. Seventy-eight percent were symptomatic less than three months. Approximately equal numbers of patients presented with T1, T2, and T3 tumors. Twenty-seven percent had cervical metastases when initially seen. The majority (89%) of patients were treated with radiation initially and the remainder (11%) received radiation therapy at the time of postsurgical recurrence with an absolute five year survival of 33%. Patients less than 60 years of age and those with small primary tumors and no neck metastases demonstrated better survival. Radiation therapy to the primary tumor and neck appears to be the preferred modality of initial treatment.     

A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction

PURPOSE: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. METHODS AND MATERIALS: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. RESULTS: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p = 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. CONCLUSION: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective in controlling the ipsilateral neck disease.     

Effects of argipressin injected into medial amygdaloid body on blood pressure and heart rate in rats

Thirteen patients with primary carcinoma of the hard palate were seen over an 18-year period at the Mallinckrodt Institute of Radiology. Nine patients had adenoid cystic carcinoma, three had squamous cell carcinoma, and one patient had mucoepidermoid carcinoma. The median tumor size was 3 cm3. The patients were clinically staged: T = 1, T2 = 5, T3 = 3, T4 = 4. All were N0M0. Ten patients underwent excision and postoperative irradiation. The remaining three patients were treated definitively with radiotherapy. The 10-year disease-free survival is 77% with an actuarial local control rate of 92%. Patients with negative surgical margins had an improved local control and disease-free survival. Duration of radiation therapy, total tumor dose or histology had no impact on outcome. We conclude that combined surgery and irradiation gives good 10-year local control and disease-free survival rates in patients with this disease.     

Successful treatment of solitary extracranial metastases from non-small cell lung cancer

BACKGROUND: Recurrence after resection of non-small cell lung carcinoma is generally associated with a poor outcome and is treated with either systemic agents or palliative irradiation. Recently, long-term survival has been reported after resection of isolated brain metastases from non-small cell lung carcinoma, but resection of other metastatic sites has not been explored fully. METHODS: We have identified 14 patients who had solitary extracranial metastases treated aggressively after curative treatment of their non-small cell lung carcinoma. The histology was squamous carcinoma in 5, adenocarcinoma in 8, and large cell carcinoma in 1. Initially, 3 patients had stage I, 5 stage II, and 6 stage IIIa disease. RESULTS: The sites of metastases included extrathoracic lymph nodes (six), skeletal muscle (four), bone (three), and small bowel (one). The median disease-free interval before metastases was 19.5 months (range, 5 to 71 months). Complete surgical resection of the metastatic site was the treatment in 12 of 14 patients. Two patients received only curative irradiation to the metastatic site, with complete response. The overall 10-year actuarial survival (Kaplan-Meier) was 86%. To date, 11 patients are alive and well after treatment of their metastases (17 months to 13 years), 1 has recurrent disease, 1 died of recurrent widespread metastases, and 2 died of unrelated causes. CONCLUSION: Long-term survival is possible after treatment of isolated metastases to various sites from non-small cell lung carcinoma, but patient selection is critical.     

Changes in epidemic patterns of Kawasaki disease in Japan

Cholangiocarcinoma is the second most common primary tumor of the liver after hepatocellular carcinoma and accounts for 5 to 25% of primary hepatic malignancies. Patients with intrahepatic or peripheral cholangiocarcinoma (ICC) most often present at an advanced stage leading to a poor prognosis. A review of the literature has produced only 10 patients who have survived over five years. We review the case of a young woman with a large cholangiocarcinoma, who has been disease free for eight years. The patient was treated with a right hepatic lobectomy, and received 4 cycles of 5-fluorouracil and levamisole postoperatively. Known factors associated with longer survival in patients with ICC include lack of evidence of local invasion (i.e. capsular, lymphatic, or vascular), negative margins, mucoblia, and well differentiation of the tumor, as well as the absence of lymph node metastases. Our patient had negative margins and lymph nodes, and showed no local invasion. However, no mucobilia was noted, and the tumor was only moderately differentiated. Young age has never been associated with increased survival. ICC remains a relatively uncommon tumor with an insidious onset and late presentation contributing to poor survival. Surgical resection remains the only therapeutic option. Since few patients are potentially resectable at the time of presentation, efforts at early diagnosis and options for adjuvant therapy are imperative.     

Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated with radioiodine

From 1969 to 1990 there were 309 patients with differentiated thyroid carcinoma (241 papillary and 68 follicular) treated with radioactive iodine for functioning node metastases alone (n = 191) or distant metastases (n = 118) with or without node metastases. These patients represented 32.7% of 945 patients treated in our institution during the same period. Initial treatment included near-total thyroidectomy and 131I ablation of postsurgical thyroid residue, followed by L-thyroxine suppressive therapy. At the end of follow-up (mean 5.8 years), 146 patients (76.4%) in the group with nodal metastases were considered cured, as assessed by clinical and laboratory evaluation including whole body scan (WBS) and serum thyroglobulin (Tg) levels; 32 patients (16.7%) had persistent disease. Loss of 131I uptake in persistent metastatic lesions occurred in five patients (2.6%), and newly developed distant metastases occurred in eight patients (4.2%). Of the patients with distant metastases, 36.4% were cured by 131I. Distant metastases from papillary carcinomas had a higher cure rate than follicular carcinomas (p < 0.01). The metastases of four patients (5.2%) lost the property to take up radioiodine. Lung and bone metastases detectable by WBS but not by radiography were most likely to be cured by 131I. The overall survival at the end of follow-up was 95.8% in patients with only lymph node metastases and 76.0% in those with distant metastases. Tumor-related deaths were 3.6% and 23.7%, respectively. Our data indicate that 131I therapy is highly effective in the treatment of lymph node metastases from differentiated thyroid carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinative factors of biochemical cure after primary and reoperative surgery for sporadic medullary thyroid carcinoma

Normalization of calcitonin levels after surgery has been regarded as the most powerful prognostic factor for medullary thyroid carcinoma (MTC). Although the prognosis of patients with persistent hypercalcitoninemia may be acceptable, the biochemical cure rate can be improved by new microdissection techniques. This raises certain questions: Can extension of locoregional lymphadenectomy (LA) further improve biochemical cure and survival after primary or reoperative MTC surgery? Which factors concerning TNM categories are associated with the possibility of postoperative normalization of calcitonin levels? This study included 64 patients with sporadic MTC operated on from 1986 to 1997. Altogether 27 patients underwent primary surgery, and 37 patients were reoperated, performing a microdissection of all four locoregional compartments (four-compartment lymphadenectomy, or 4CLA). For primary MTC the biochemical cure rate was 100% in node-negative patients and 33% in node-positive patients; the latter could be improved to 45% after 4CLA. In contrast to reoperative MTC, the rate of lymph node metastases (LNMs) with primary MTC correlated with the pT category (pT1 33%, pT2 53%, pT3 100%, pT4 100%) but not with age or sex. Again in contrast to reoperative MTC, mediastinal LNMs in primary MTC were present only in patients with a pT4 tumor. At reoperation, 4CLA was able to cure 22% of node-positive patients, 28% without proved distant metastases. No patient with extrathyroidal tumor involvement or distant metastases was biochemically cured after either primary or reoperative surgery. For all node-positive MTC patients, in addition to cervicocentral LA at least a bilateral cervicolateral LA is recommended. Transsternal mediastinal lymph node dissection is indicated in patients with LNMs in the cervicomediastinal transition, facilitating biochemical cure in up to 45% after the first operation and 22% after reoperative surgery of sporadic MTC.     

Identification of autolysosomes directly associated with proteolysis on the density gradients in isolated rat hepatocytes

BACKGROUND: More than 40% of patients who undergo curative resection of advanced colorectal carcinoma can be expected to have recurrence of the disease. The most frequent sites of recurrence are the liver (33% of patients) and lung (22%). Interest has therefore focused on treating hepatic or pulmonary metastases, or both, to improve the outcomes of these patients. Although surgical resection has become an increasingly accepted treatment for resectable localized hepatic or localized pulmonary metastases from colorectal carcinoma, the value of aggressive surgery for the removal of both hepatic and pulmonary metastases from patients with primary colorectal carcinoma remains to be clarified. METHODS: Data on 30 patients who had undergone resection of both hepatic and pulmonary metastases from colorectal carcinoma were included in the study. RESULTS: Independent, significant prognostic features were found to be the time that hepatic or pulmonary metastases occurred and the distribution of pulmonary metastases. Median survival times were 30 months (range, 7-108 months) after resection of both hepatic and pulmonary metastases and 48.5 months (range, 11-149 months) after excision of the primary colorectal tumor. Actuarial 1-, 3-, and 5-year survival after resection of both hepatic and pulmonary metastases was 86.7%, 49.3%, and 43.8%, respectively. No perioperative mortality occurred. There were three cases of minor morbidity, which the authors considered acceptable. CONCLUSIONS: Resection of both hepatic and pulmonary metastases from colorectal carcinoma may help to prolong the survival of a small group of patients with these metastases.     

Ovarian metastases from primary gastrointestinal malignancies: the Royal Marsden Hospital experience and implications for adjuvant treatment

We investigated the pattern and frequency of ovarian metastases in patients with primary gastrointestinal malignancies and evaluated the response to surgery, chemotherapy and in three cases radiotherapy. The literature reports that this group of patients have a poor prognosis, but no report has specifically addressed the response to chemotherapy. Using a database which is generated prospectively, we analysed 51 patients with primary gastrointestinal malignancies and ovarian metastases. All patients received chemotherapy but only 36 were evaluable for response; five had adjuvant treatment and ten had non-measurable disease. Seventeen patients had surgical oophorectomy and three patients received radiotherapy. The overall response rate to chemotherapy was 22%; eight partial responses and no complete responses. When stratified according to site of response, 11 (31%) patients had a partial response at sites of extraovarian metastases and only five (14%) had a partial response in the ovaries. Seven patients with primary colorectal cancer had a differential response in favour of extraovarian sites. The median survival was 9 months for the 51 patients. Three premenopausal women with resected gastric carcinoma received adjuvant chemotherapy and relapsed only in the ovaries. In primary colorectal tumours the response of ovarian metastases to chemotherapy is less than that for other sites. Therefore, the ovary may be a sanctuary site for metastases which has important implications for adjuvant chemotherapy in women. These women could be followed up regularly by transvaginal ultrasonography to detect such metastases at an early stage when they would be amenable to surgical resection. Surgery should be considered for selected patients who develop metachronous metastases, as patients may be rendered disease free for several months.     

Uveal metastasis from carcinoid tumor. Clinical observations in nine cases

BACKGROUND: Carcinoid tumor is a low-grade malignancy that usually arises in the gastrointestinal tract or bronchus and rarely metastasizes to the eye. Metastasis of carcinoid tumor to the uvea can be confused clinically with other primary and metastatic uveal tumors. METHODS: The authors reviewed the records of 410 consecutive patients with uveal metastases referred to the Ocular Oncology Service at Wills Eye Hospital to identify those in whom carcinoid tumor was the primary neoplasm. The authors evaluated the clinical features of these metastases. RESULTS: Of 410 consecutive patients with uveal metastases, the primary neoplasm was a carcinoid tumor in 9 (2.2%). There were four men and five women. The mean age at ocular diagnosis was 50 years. In five patients (56%), the primary tumor was undiagnosed at ocular presentation. In the other four patients, the mean time interval from diagnosis of the primary carcinoid tumor to uveal metastasis was 89 months (range, 55-180 months). The site of the primary carcinoid tumor was the bronchus in seven patients, the esophagus in one, and the thymus in one. The site of intraocular metastasis was the choroid in six patients, the ciliary body in two, and the iris in one. All choroidal tumors had a characteristic orange color. Initial ocular treatment included external beam radiotherapy in five patients, plaque radiotherapy in two, argon laser photocoagulation in one, and local resection in one. Ocular tumor control was achieved in each patient. After a mean follow-up of 34 months, four patients (44%) are still alive. Five patients have died, with a mean survival of 34 months (range, 2-104 months) after the diagnosis of uveal metastasis. CONCLUSIONS: Uveal metastasis from carcinoid tumor is rare and tends to arise from the bronchus. Clinically, it has a distinctive orange color and may be associated with a longer systemic survival, compared with uveal metastasis from other primary sites.     

Structure-function studies on the inhibition of binding of alpha-thrombin to platelet GpIb alpha by the peptide D-Y-Y-P-E and the artifactual inhibitory activity of C-terminal E in this peptide

In papillary thyroid carcinoma lymphnode metastases at presentation do not seem to adversely affect survival, but do increase the risk of loco-regional tumor recurrence. The value of systematic versus selective lymphadenectomy is far less standardized, whereas the role of postoperative radioiodine in preventing either nodal recurrence or cancer death remains controversial. Clinical data of 36 N+ patients with papillary thyroid carcinoma who had undergone from 1990 to 1996 ipsilateral or bilateral neck dissection were retrospectively reviewed, to analyse the value of systematic lymphadenectomy. In our series of 50 extensive lymph node dissections (levels 2-6), the number of metastases in each specimen (mean value: 5) and the incidence of multiple level metastases (36%) were high. In 37.5% of the metastases at level 6 and in 11.1% at level 4, coexisting nodal involvement at level 2 was observed, without metastasization at intermediate levels. Multiple levels metastases and skip metastases were present in at least one third of the patients and could be excised only performing a complete dissection of the levels 2-6. Extra-capsular spread was found in 56% of the specimens. In 64.3% of these cases a functional neck dissection was performed. A modified radical or radical neck dissection was carried out in the other 35.7% of the cases. These patients received modified radical neck dissection (functional dissection with sacrifice of internal jugular vein) in 60% of the cases and radical neck dissection in the other 40%. In papillary thyroid carcinoma extensive lymphnode dissection at presentation has been stated to offer no advantage versus selective lymphadenectomy, causing increased morbidity. However, experienced surgeons report a low incidence (less than 5%) of accessory spinal nerve and cervical plexus permanent sequelae after functional neck dissection. In our opinion, patients with cervical lymph node metastases require a complete loco-regional neck dissection. Systematic lymphadenectomy, performed by lateral neck plus upper anterior mediastinal dissection, can yield a high disease-free survival. Moreover, this can limit the overall radio-iodine therapeutic dose and the risk of de-differentiation of recurrent tumor to the anaplastic type in patients with a long-term and near normal life-span.     

DNA cytophotometry and prognosis in typical and atypical bronchopulmonary carcinoids. A clinicomorphologic study of 100 neuroendocrine lung tumors

Surgical material obtained from 100 patients with typical carcinoids (TC) and atypical carcinoids (AC) of the lung (including 100 primary, four residual tumors, and four lymph node or distant metastases) was investigated by conventional histology and scanning DNA cytophotometry. Of the 60 TC (96%), 58 exhibited euploid DNA histograms compared with only 20 (50%) of the 40 AC. The morphologic findings were related to the patients' survival (median observation period, 9 years). Statistical analyses disclosed the histologic type of disease (TC versus AC) and the DNA content of tumors (euploid versus aneuploid) to affect prognosis significantly (p < 0.001). Deaths resulting from tumor were exclusively observed among patients with atypical (eight of 40) or DNA aneuploid carcinoids (eight of 22). Six patients were alive with persistent tumor manifestations 3 to 20 years after initial diagnosis, four with DNA diploid primary carcinoids. The presence of lymph node metastases alone was not associated with poor prognosis as long as the primary tumor or the related metastases showed a diploid DNA content. DNA cytophotometry thus might be regarded as an adjunctive prognostic criterion in individual carcinoid cases.     

Radiation therapy enhances the therapeutic effect of immunotherapy on pulmonary metastases in a murine renal adenocarcinoma model

In order to improve the efficacy of immunotherapy, we have evaluated the effects of radiation therapy combined with interleukin 2 (IL-2) treatment in a murine metastatic renal adenocarcinoma model (Renca). Pulmonary metastases were induced in Balb/c mice by intravenous injection of Renca and five days later a sublethal dose of radiation (300 rads) was administered either to the whole body or to the left lung only. One day following radiation, immunotherapy was given for 5 consecutive days of IL-2 at 5,000 Cetus units intraperitoneally, twice daily. The animals were either sacrificed on day 23 or 33 to assess tumor burden, or were followed for long term survival. We found that pretreatment with irradiation greatly enhanced the therapeutic efficacy of immunotherapy and was manifested by a significant reduction in pulmonary metastases and an increase in survival. When combined with immunotherapy, local tumor irradiation was not only as effective as whole body irradiation, but irradiation of one lung reduced the number of metastases similarly in both lungs. This suggests that local tumor irradiation may act through a systemic mechanism to increase the anti-tumor response mediated by IL-2 therapy.     

Tape stripping induces marked epidermal proliferation and altered TGF-alpha expression in non-lesional psoriatic skin

PURPOSE: This study was performed to establish the classification and the treatment modality for recurrent cervical cancer of the vaginal stump after hysterectomy. PATIENTS AND METHODS: Ninety patients with centrally recurrent cervical cancer of the vaginal stump following hysterectomy were treated with high-dose-rate intracavitary brachytherapy with or without external irradiation. The intervals between primary surgery and vaginal recurrences varied from 3 months to 36 years. Tumor size of the vaginal stump was determined by bimanual rectovaginal examination at the time of recurrence and was classified into three groups, i.e., small (no palpable tumor), medium (less than 3 cm), and large (3 cm or more). RESULTS: The 10-year survival rates for all patients were 52%. Survival was greatly influenced by the tumor sizes of the vaginal stump. The 10-year survival rates of patients with small, medium, and large size tumors were 72, 48, and 0%, respectively. All patients with large size tumors died within 5 years. Of 90 patients, 75 (83%) were determined by physical examination to be free of tumor on at least one visit within 2 months of the completion of treatment (CR). The remaining 15 patients (17%) had physical findings suggestive of residual tumor (Residual). The overall 10-year survival rate for all patients with CR was 63%, compared with 10% for the patients with Residual (P < 0.0001). The incidences of distant metastases of the patients with or without local failure were 55 and 13%, respectively (P < 0.0001). The patients with local failure had significantly higher incidence of metastases. Most patients with small size tumor were treated with brachytherapy alone, and the survival rates of these patients were not improved by combination with external irradiation. CONCLUSION: These results suggest that tumor size was a significant prognostic factor for recurrent cervical cancer of the vaginal stump. Patients with small size tumors were recommended to be treated with brachytherapy alone.