Showing papers in "Cancer in 1992"

Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation.

Abstract: Background. Prostate cancer is the most prevalent nonskin cancer among men in the United States and is the second leading cause of cancer deaths in men, The cause of prostate cancer remains obscure. Recently it was hypothesized that low levels of vitamin D, a hormone with potent antitumor properties, may increase the risk for clinical prostate cancer. Methods. Because the major source of vitamin D is casual exposure to ultraviolet (UV) radiation, the authors examined the geographic distributions of UV radiation and prostate cancer mortality in 3073 counties of the contiguous United States using linear regression and trend surface analyses. Results. The geographic distributions of UV radiation and prostate cancer mortality are correlated inversely (P < 0.0001). Prostate cancer mortality exhibits a significant north-south trend, with lower rates in the South. These geographic patterns are not readily explicable by other known risk factors for prostate cancer. Conclusions. These data lend support to the hypothesis that UV radiation may protect against clinical prostate cancer. Viewed in conjunction with other recent data, including those demonstrating a differentiating effect of vitamin D on human prostate cancer cells, these findings suggest that vitamin D may have an important role in the natural history of prostate cancer.

Aneurysmal bone cyst. A clinicopathologic study of 238 cases.

Abstract: Aneurysmal bone cyst (ABC) is a nonneoplastic expansile bone lesion that mainly affects children and young adults. Primary ABC is relatively rare, with an incidence one half that of giant cell tumor of bone. In 238 patients with ABC studied in the Mayo Clinic files, more than 80% of the lesions were in long bones, flat bones, or the spinal column. Of the lesions initially treated at the Mayo Clinic, 95% were typical ABC; the rest were "solid" variants. Except for the absence of obvious cavernous channels and spaces, there was no significant histologic difference between solid variant and typical ABC. Radiographically, ABC is an eccentric expansile lesion commonly located at the metaphysis of long bones. Computed tomography and magnetic resonance imaging may show multiple internal septations or fluid levels. In the 153 patients treated, 19% had recurrence after curettage (intralesional excision). Recurrence was most common during the first 2 postoperative years.

Primary sarcomas of the heart.

Abstract: Seventy-five primary sarcomas of the heart were classified by histologic appearance as angiosarcoma (26 cases), undifferentiated sarcoma (18 cases), osteosarcoma (9 cases), fibrosarcoma (6 cases), malignant fibrous histiocytoma (6 cases), leiomyosarcoma (4 cases), myxosarcoma (3 cases), synovial sarcoma (2 cases), and neurofi-brosarcoma (1 case). The ages of the patients ranged from 1 to 75 years at the time of presentation (mean, 39 years). Angiosarcomas were predominantly right-sided and osteosarcomas left-sided. Forty patients treated surgically were examined, and survival correlated with clinical and histologic parameters. The survival rate was poor, with a mean of 11 months and median of 6 months. By univariate analysis, the survival rate was more favorable for patients with tumors located on the left side of the heart, without necrosis, with a low mitotic count, and without metastasis at diagnosis. Survival rates were better in patients receiving chemotherapy and radiation therapy. Age, gender, presence of differentiation, and histologic type did not affect prognosis. By multivariate analysis, a low level of mitotic activity and any therapy were the only significant factors affecting survival rate. Immunostaining with commercially available antisera was useful in the diagnosis of sarcoma but not in subclassification of 19 tumors so tested. Although the prognosis for patients with cardiac sarcomas is dismal, histologic grading is useful in predicting outcome, as has been shown for soft tissue sarcomas of other sites.

Characterization of 21 newly established esophageal cancer cell lines

Abstract: Twenty-one esophageal cancer cell lines (KYSE series) have been established from the resected specimens of patients with esophageal cancer. Three lines, KYSE-30, KYSE-50, and KYSE-70, were derived from the implanted tumor of nude mice (initial passage); others were derived from resected specimens. Each cell line was morphologically distinct. Detailed cytogenetic analysis indicated that each cell line was karyotypically unique, and DNA fingerprint analysis showed no cross-contamination among cells. Doubling time ranged from 13.7 to 75.5 hours, and modal chromosome numbers ranged from 46 to 120. Most cell lines grew in monolayer, but two cell lines (KYSE-50 and KYSE-360) grew as floating cell aggregates. No correlation was demonstrated between the establishment of cell lines and cell differentiation. These cell lines are the first reported to be homogeneous and individually unique and may provide a useful model for the study of human esophageal cancer.

The WHO Histological Typing of Odontogenic Tumours. A commentary on the Second Edition.

Abstract: This article introduces the revised World Health Organization (WHO) classification of odontogenic tumors and jaw cysts and certain bone lesions that either are peculiar to the jaws or have distinctive features in that location. The new and revised classification is compared with the previous version, the reasons for the changes are outlined, and reference is made to a number of newly characterized lesions that have been included.

Primary liver cancer in Japan

Abstract: . Proceedings of JSUM 51:273-274 44. Deixonne B, Makuuchi M, Pissas JM (1988) Ultrasonography of the liver. In: Deizonne B, Lopez FM (eds) Operative ultrasonography. Springer-Verlag, Berlin 45. Tanaka M, Suto T, Kunikane M, Moriyama Y, Kondoh H, Soejima Y, Sasaki D, Yoshida Y (1988) Angiographic pooling findings in cases with hypo echoic hemangiomas of the liver (English abstract). Jpn J Ultrasonics 15:221-230. Jpn J Ultrasonics 15:221-230 46. Takehara Y, Nomura M, Matsukawa S, Yasuda T, Yamashita K, Tanaka I, Matsuzawa K, Kojima M, Ohno Y, Matsuda M (1987) Diagnosis of the ultrasonogram: Focal nodular hyperplasia (FNH) (in Japanese). Rinsyou Syoukaki Naika 2:13251330 47. Oda T, Sakaguchi S, Okumura M (1990) A case of focal nodular hyperplasia of the liver: Study on diagnostic imaging (English abstract). Fukubu Gazou Shin dan 10:81-87 48. Morita S, Okajima K, Tamio T, Kubokawa M, Matsui A, Nakata E, Nakajima T, Ishiga N (1987) A case of focal nodular hyperplasia of the liver and the review of previously reported 44 cases in Japan (in Japanese). Jpn J Gastroent 84:302-306 49. Freeman MP, Vick CW, Taylor KJW, Carithers RL, Brewer WH (1986) Regenerating nodules in cirrhosis: Appearance with anatomic correlation. AJR 146:533-536 50. Ida M, Kitagawa K, Kawamura I, Matsui 0, Takashima T, Shinmura K, Kinami Y, Shinozaki K (1984) A case report of regenerative nodule in liver cirrhosis: Ultrasonographically mimicking hepatocellular carcinoma (English abstract). Acta Hepatol Jpn 25:400-404 51. Lee S, Fujita N, Yano A, Kobayashi G, Chon an A, Mochizuki F (1988) A case of hyperechoic regenerating nodules mimicking hemangioma of the liver (English abstract). Jpn J Med Ultrasonics

Carcinoma of the gallbladder. Histologic types, stage of disease, grade, and survival rates.

Abstract: Data on patients with gallbladder cancer listed in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were reviewed. Between 1977 and 1986, 3038 patients were recorded in the Program. Histologic grade, histologic type, stage of disease, and vascular invasion were correlated with outcome. Compared with all other histologic types of cancer, papillary carcinomas had the most favorable prognosis. The 2-year survival rate for patients with papillary carcinoma was 47%. A correlation with survival existed between grade, stage of disease, and vascular invasion. The study confirmed that cancers of the gallbladder occur more often in older age groups and are more common in women. Almost 40% of cases are found at an advanced stage. For patients whose enolase tumor was limited to the gallbladder at the time of surgery, the 2-year survival rate was 45% and the 5-year rate was 32%.

Percutaneous Ethanol Injection in the Treatment of Hepatocellular Carcinoma in Cirrhosis. A Study on 207 Patients

Abstract: In 207 cirrhotic patient carriers of hepatocellular carcinoma (HCC), percutaneous ethanol injection (PEI) was administered with ultrasound guidance. The patients were classified as Child's Class A, 136; B, 54; and C, 17. Their mean age was 63.5 years, and the male-female ratio was 3.5:1. There was a single HCC less than 5 cm in diameter in 162 patients; 45 had more than one HCC. The follow-up ranged from 5 to 71 months (mean, 25 months). No noteworthy complications occurred during or after 2485 treatments. The 1-year, 2-year, and 3-year survival percentages (by the Kaplan-Meier method) for the patients with one HCC were 90%, 80%, and 63%, respectively. The corresponding percentages by Child's class were 97%, 92%, and 76% for Class A; 88%, 68%, and 42% for B; and 40%, 0%, and 0% for C. The 1-year, 2-year, and 3-year survival rates for patients with more than one HCC were 90%, 67%, and 31%, respectively. These results were similar to those found by others and showed that PEI was a safe, reproducible, easy-to-do, and low-cost therapeutic technique. In terms of survival, these PEI results were better than the published results of no treatment and equivalent to those of surgery. In uncontrolled series, bias can play an important role. Therefore, additional trials would be useful. Cancer 1992; 69: 925–929.

Genetic alterations in the adenoma--carcinoma sequence.

Abstract: Tumorigenesis is thought to be a multistep process in which genetic alterations accumulate, ultimately producing the neoplastic phenotype. A model was proposed to explain the genetic basis of colorectal neoplasia that included several salient features. First, colorectal tumors appear to occur as a result of the mutational activation of oncogenes coupled with the inactivation of tumor-suppressor genes. Second, mutations in at least four or five genes are required to produce a malignant tumor. Third, although the genetic alterations often occur in a preferred sequence, the total accumulation of changes, rather than their chronologic order of appearance, is responsible for determining the tumor's biologic properties. Several different genetic alterations were identified that occur during colorectal tumorigenesis. Activational mutation of the ras oncogene was found in approximately 50% of colonic carcinomas and in a similar percentage of intermediate-stage and late-stage adenomas. Allelic deletions were discovered of specific portions of chromosomes 5, 17, and 18, which presumably harbor tumor-suppressor genes. The target of allelic loss events on chromosome 17 has been shown to be the p53 gene, which is mutated, not only in colonic cancer, but also in a large percentage of other human solid tumors. The gene dcc recently was identified; this candidate tumor-suppressor gene on chromosome 18 appears to be altered in colorectal carcinomas. The protein encoded by the dcc gene has significant sequence similarity to neural cell adhesion molecules and other related cell-surface glycoproteins. By mediating cell-cell and cell-substrate interactions, this class of molecules may have important functions in mediating cell growth and differentiation. Alterations of the dcc gene may interfere with maintenance of these controls and thus may play a role in the pathogenesis of colorectal neoplasia. Another candidate tumor-suppressor gene also was identified on chromosome 5, mcc (for mutated in colorectal cancers). The mcc genetic alterations include one tumor with somatic rearrangement of one mcc allele and several tumors with somatically acquired point mutations in the coding region. Studies currently are ongoing to (1) identify additional tumor-suppressor gene candidates, (2) increase our understanding of normal tumor-suppressor gene function, and (3) demonstrate the functional tumor-suppressor ability of these genes both in vivo and in vitro.

Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications.

Abstract: Endocrine-paracrine cells of the prostate (also known as APUD or neuroendocrine cells) constitute, in addition to the basal and exocrine secretory cells, a third population of highly specialized epithelial cells in the prostate gland. These endocrine-paracrine cells contain, and most likely secrete, serotonin and calcitonin, as well as variety of other peptides. Little is known of the functional role of these cells, but they probably subserve a paracrine or local regulatory role. They may also regulate via endocrine, lumencrine, or neurocrine mechanisms. These endocrine-paracrine cells probably play a significant role during prostatic growth and differentiation as well as regulating the secretory process of the mature gland. Neuroendocrine differentiation in prostatic carcinoma occurs in the form of the relatively rare small cell carcinoma and carcinoid or carcinoid-like tumor, but most commonly as focal neuroendocrine differentiation in a conventional prostatic adenocarcinoma that is a very frequent, if not ubiquitous phenomenon, and reflects tumor cell heterogeneity mimicking the normal differentiation process. The world's literature on neuroendocrine differentiation in prostatic carcinoma is reviewed. Neuroendocrine differentiation in all types of prostatic carcinoma appears to correlate with a poor prognosis. This correlation is probably multifactorial and may relate to a positive correlation with grade, a direct resistance to hormonal manipulation, and/or autocrine/paracrine growth factor activity due to the secretion of neuroendocrine products. Neuron-specific enolase and chromogranin, as well as other neuroendocrine products, may be useful as serum markers in patients with prostatic carcinoma with neuroendocrine differentiation. New therapeutic strategies need to be developed to treat these tumors. This includes the use of specialized protocols that have been effective against neuroendocrine carcinomas arising in other organ systems.

Breast conservation versus mastectomy. Is there a difference in psychological adjustment or quality of life in the year after surgery

Abstract: Women with a breast cancer diagnosis often are given a choice between breast conservation or mastectomy as the primary treatment for their cancer. Despite the high frequency of this cancer, there is little systemic information about the effect of surgical treatment on the quality of life or psychological adjustment of the patient. In this study, the authors prospectively evaluated quality of life, performance status, and psychological adjustment in 109 women who had primary breast cancer treatment. During the year of follow-up, no statistically significant differences in quality of life, mood disturbance, performance status, or global adjustment were found between the two surgical groups, and both groups of patients improved significantly during the year of observation (P = 0.0001). As was predicted, patients receiving mastectomy reported more difficulties with clothing and body image; however, these results apparently did not affect the assessment of mood or quality of life. The authors conclude that patients receiving breast conservation therapy do not experience significantly better quality of life or mood than patients having mastectomy; however, patients having breast conservation surgery have fewer problems with clothing and body image. Women receiving breast conservation therapy may require more intensive psychosocial intervention in the postoperative period because of the added burden of primary radiation therapy.

The World Health Organization's Histological Classification of Salivary Gland Tumors. A commentary on the second edition.

Abstract: The second edition of the World Health Organization's Histological Classification of Salivary Gland Tumors is more extensive and detailed than the previous edition published 20 years ago. The new edition is based on data regarding newly described tumor entities and the behavior and prognosis of the previously classified tumors. The distinct morphologic features of monomorphic adenomas justify their separation for purposes of identification. Among the carcinomas, various types were distinguished for purposes of recognition, prognosis, and treatment. The term tumor was replaced by carcinoma in the following two entities: acinic cell carcinoma and mucoepidermoid carcinoma. The tumor-like lesions were described in more detail.

Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients

Abstract: Background Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. Herein, the authors report a series of 64 patients with small cell carcinoma of the urinary bladder. Methods Histologic slides and medical records from 64 patients with small cell carcinoma of the urinary bladder were reviewed for morphologic, demographic, and clinical data. All patients fulfilled the criteria established for small cell carcinoma according to the World Health Organization classification system. The 2002 tumor, lymph node, and metastasis (TNM) system was used for pathologic staging. The correlations of various clinicopathologic characteristics with survival were analyzed. Results Patients ranged in age from 36 years to 85 years (mean age, 66 years). The male-to-female ratio was 3.3:1.0. Among patients with clinical information available, 65% had a history of cigarette smoking, and 88% presented with hematuria. All but one patient had muscle-invasive disease at presentation. Thirty-eight patients (59%) underwent cystectomy. Sixty-six percent of patients had lymph node metastasis at the time of cystectomy. Twenty patients (32%) had pure small cell carcinoma, and 44 patients (68%) had small cell carcinoma with other histologic types (35 patients had urothelial carcinoma, 4 patients had adenocarcinoma, 2 patients had sarcomatoid urothelial carcinoma, and 3 patients had both adenocarcinoma and urothelial carcinoma). With a mean follow-up of 21 months, 68% of patients died of bladder carcinoma. None of the clinicopathologic parameters studied (age, gender, presenting symptoms, smoking history, the presence of a nonsmall cell carcinoma component, chemotherapy, or radiation therapy) were associated with survival. No significant survival difference was found between patients who did and did not undergo cystectomy (P = 0.65). Patients who had organ-confined disease had marginally better survival compared with patients who had nonorgan-confined disease (P = 0.06). The overall, 1-year, 18-month, 3-year, and 5-year disease-specific survival rates were 56%, 41%, 23%, and 16%, respectively. Conclusions The prognosis for patients with small cell carcinoma of the urinary bladder remains poor, even though the overall survival for patients with bladder carcinoma has improved significantly over the last decade.

Family history and the risk of stomach and colorectal cancer

Abstract: Background. The role of a family history of selected neoplasms in first-degree relatives in the risk of gastrointestinal cancers has been investigated, but requires further quantification. Methods. A case-control study was conducted in northern Italy on 628 histologically confirmed incident cases of stomach cancer, 766 cases of colon cancer, 456 cases of rectal cancer, and 1766 controls admitted to hospital for acute, nonneoplastic, non-digestive tract disorders. Results. Significant associations were observed between a family history of gastric cancer and stomach cancer risk (relative risk [RR], 2.6), and between a family history of intestinal cancer and colon (RR, 2.4) and rectal cancer (RR, 1.7). There was a tendency for the risks to be above unity for a family history of stomach cancer and for a number of other cancer sites (including esophagus, intestines, liver, pancreas, gallbladder, and lung), and the RR were of borderline statistical significance for cancer of the liver and intestines. The RR for a family history of lung cancer was 1.5 for stomach, 1.2 for colon, and 1.3 for rectal cancer, with none of the estimates being significant. There was no consistent pattern of risk with reference to the type of first-degree relationship; the RR was similar for stomach cancer with reference to parents and siblings, and for colon and rectal cancer, it was only moderately higher with reference to siblings. Significant trends in risk with the number of first-degree relatives were observed for all three cancer sites investigated. Conclusions. In terms of population attributable risk, approximately 8% of stomach cancers and 3% of colorectal cancers would be related to this familial component.

Pathology and prognosis of gastric carcinoma. Findings in 10,000 patients who underwent primary gastrectomy.

Abstract: Background. Despite recent advances in diagnosis and treatment, gastric carcinoma remains a major cause of death in the world. Methods. The clinicopathologic profile of 10,000 consecutive patients who underwent primary gastrectomy during 1962-1989 were reviewed and prognostic factors influencing survival in those with gastric carcinoma were analyzed in 7031 patients. Results. Incidence of gastrectomy for carcinoma has increased steadily and the rate of early carcinoma exceeded that of advanced carcinoma in the recent period of 1985-1989. Five-year and 10-year survival rates were 46.1% and 35.2% in 3868 patients with advanced carcinoma, and 88.8% and 77.3% in 3163 patients with early carcinoma, respectively. In patients with advanced carcinoma, significantly poorer survival rates were noticed for patients older than 70 years of age, those who underwent total gastrectomy, tumors involving the entire stomach or greater than 10 cm in diameter, a macroscopic diffusely infiltrative pattern, adenosquamous histologic type, positive surgical resection margins, or lymph node metastasis. None of the above poor prognostic features were identified in patients with early gastric carcinoma group except for those older than 70 years of age. Although lymph node metastases were present in 10% of early gastric carcinomas, this feature did not impart a poor prognosis. Patients with advanced carcinoma grossly resembling an early carcinoma had an intermediate prognosis, suggesting the existence of a developmentally midstage lesion between early and advanced carcinoma. Conclusions. The study illustrates that the most important role for clinicians treating with gastric carcinoma should be early detection and aggressive surgery for resectable tumors, followed by detailed pathologic examination.

The indications for elective treatment of the neck in cancer of the major salivary glands

Abstract: To define the indications for elective neck treatment, the cases of 474 previously untreated patients were reviewed who had locally confined major salivary gland cancers treated between 1939 and 1982. Clinically positive nodes were present in 14% (67 of 474). Overall, clinically occult, pathologically positive nodes occurred in 12% (47 of 407). By univariate analysis, several factors appeared to predict the risk of occult metastases; however, multivariate analysis revealed that only size and grade were significant risk factors. Tumors 4 cm or more in size had a 20% (32 of 164) risk of occult metastases compared with a 4% (nine of 220) risk for smaller tumors (P less than 0.00001). High-grade tumors (regardless of histologic type) had a 49% (29 of 59) risk of occult metastases compared with a 7% (15 of 221) risk for intermediate-grade or low-grade tumors (P less than 0.00001). In view of the low frequency of occult metastases in the entire group, routine elective treatment of the neck is not recommended. High-grade tumors and larger tumors have a high rate of occult neck metastases, and treatment should be considered in this group.

A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer.

Abstract: A significant increase in the dose intensity of chemotherapy with fluoropyrimidines and platinum complexes has resulted from selective circadian timing and/or circadian modulation of the infusion rate. The relevance of such chronopharmacologic strategy for improving the outcome of metastatic colorectal cancer was evaluated in an extended Phase II clinical trial involving 93 patients. Of these, 49% previously had received chemotherapy and/or radiation therapy. The drugs 5-fluorouracil (5-FU, 700 mg/m2/d) and folinic acid (FA, 300 mg/m2/d) combined with oxaliplatin (l-OHP, a nonnephrotoxic platinum complex, 25 mg/m2/d) were infused continuously for 5 days every 3 weeks. In a pilot randomized study, the infusion of all three drugs at a constant rate resulted in World Health Organization (WHO) Grade 3 or 4 toxicity in all four patients compared with no such toxicity in four patients if the infusion rate was modulated according to circadian rhythms. In this Phase II trial, drug delivery was modulated sinusoidally over the 24-hour day with peak flow rates at 4 AM for 5-FU and FA and at 4 PM for l-OHP, using an ambulatory programmable-in-time pump. All patients and 784 of 839 courses (93%) were evaluable for toxicity. Dose-limiting toxicities (WHO Grade 2 to 4) included diarrhea (19% of courses) and vomiting (35% of courses). In addition, WHO Grade 2 to 4 hematologic or mucosal toxicity, respectively, occurred in 2.5% and 7% of courses. Two toxic deaths were encountered. Peripheral sensory neuropathy led to discontinuation of l-OHP in 14 patients after 7 to 12 courses; it completely disappeared within 3 months. Fifty-four of the 93 patients had an objective response (58%; 95% confidence limits, 48% to 68%), irrespective of previous treatment or prior documented progression while receiving standard chemotherapy with 5-FU and FA or continuous 5-FU. Complete responses (CR) were seen in 6 patients (4 of which were proved histologically) and, after surgery, in 12 additional patients (overall CR rate, 18 of 93 [19%]; 95% confidence limits, 11% to 27%). Median progression-free survival (PFS) and overall survival were, respectively, 10 and 15 months, irrespective of prior therapy. Both PFS and survival were significantly longer in patients with a good performance status (PS, 0 or 1, by WHO criteria; respectively, 12 and 21 months) than in patients with poor PS (respectively, 8 and 10 months; P less than 0.01, by log-rank test). This chronopharmacologic protocol may have circumvented, to some extent, both the natural and acquired resistance of colorectal cancer to chemotherapy.

Mucoepidermoid carcinoma of intraoral salivary glands. Evaluation and application of grading criteria in 143 cases.

Abstract: The histopathologic criteria most useful for grading of mucoepidermoid carcinomas are controversial. To identify those histologic features most important in the grading of intraoral mucoepidermoid carcinomas, 143 cases of this disease with clinicopathologic correlations were studied. Twelve histopathologic features of each tumor and their clinical presentation were correlated with patient outcome. Seven patients died of disease, 5 had regional metastases only, 10 had recurrences only, and 121 had no additional problems. Clinical features suggesting aggressive behavior were short duration, presence of clinical symptoms, and location of tumor in the tongue and floor of the mouth. The histopathologic features that indicated high-grade behavior were an intracystic component of less than 20%, four or more mitotic figures per ten high-power fields, neural invasion, necrosis, and cellular anaplasia. The simultaneous assessment of these features showed improved prognostic correlation over individual parameters. A quantitative grading system was devised using these features. Tumors with a point score of 0 to 4 were considered low grade, and none of 122 patients with scores in this range died of their tumor, although 9 had recurrences only and 3 had regional metastases. Point scores of 7 or above indicated highly aggressive behavior. Six of ten patients with these high scores died of tumor. Most of these six patients had recurrences and regional metastases, and all had distant metastases. Two other patients had regional metastases only. Scores of 5 to 6 were considered intermediate between low-grade and high-grade scores because only 1 of 13 patients with these scores died of disease. Three of the five patients with regional metastasis had low-grade tumors, indicating the inability of the grading system to identify them. Nonetheless, with an average follow-up on these patients of 10 years after treatment of the metastasis, no patient had additional problems. The relative objectivity of our proposed grading system for intraoral mucoepidermoid carcinomas may help achieve more accurate and consistent grading of these rare tumors.

Plasmacytoma. Treatment results and conversion to myeloma

Abstract: Forty-six cases of solitary plasmacytoma were reviewed for response to radiation and progression to multiple myeloma. Cases were classified as solitary plasmacytomas of bone (SPB) (32 cases) or extramedullary plasmacytomas (EP) (14 cases). There was an overall 93% response rate of the tumor to radiation therapy: 62% had a complete response after radiation therapy, whereas 31% had a partial response. Conversion to multiple myeloma was influenced by the type of plasmacytoma; 53% of the patients with SPB converting to myeloma versus 36% of the patients with EP. Time from diagnosis to conversion for patients with SPB showed no evidence of plateau, with conversion continuing to occur even after 17 years. The median survival time for patients after conversion to myeloma was 14.5 months and was not affected by time to conversion. Serum protein level, presence of monoclonal gammopathy, and size of primary lesion were of some prognostic significance in predicting conversion to myeloma. Adjuvant chemotherapy did not affect the incidence of conversion but did appear to delay conversion to myeloma. Seven patients in whom multiple sequential solitary plasmacytomas developed formed a distinct subset, with a median time to a second plasmacytoma of 63 months. In three of these patients, conversion to myeloma occurred subsequently. This study supports the idea of EP having a lower incidence of conversion to myeloma and a different natural history from SPB, with SPB likely to be multiple myeloma in evolution.

A clinicopathologic and immunohistochemical study of gastrointestinal stromal tumors

Abstract: The clinicopathologic and immunohistochemical features in 120 cases of gastrointestinal stromal tumor (GIST) were reviewed. Excluding 24 cases of gastric schwannoma, 96 cases of GIST consisting of 62 benign tumors and 34 sarcoma (low grade, 17; high grade, 17), with 9 cases arising in the esophagus, 57 in the stomach, 28 in the small intestine, and 2 in the colon, were studied. All esophagus and colon tumors were benign and resembled a conventional leiomyoma histologically. However, the gastric and small intestine benign tumors mostly showed histologic features of cellular or epithelioid leiomyoma. Immunohistochemically, desmin caused a positive reaction in all esophagus and colon tumors, but only 26% of gastric and small intestine tumors. However, muscle-specific actin (HHF35) caused a positive reaction in most GIST (92%). The 10-year survival rates of the patients with gastric sarcoma and those with intestinal sarcoma were 74% and 17%, respectively. These results showed that histologic and immunohistochemical features were distinctly different, depending on the location in the gastrointestinal tract; that most GIST, excluding schwannoma, had smooth muscle differentiation; and that sarcomas had a more favorable prognosis when they occurred in the stomach rather than the intestine.

Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone

Abstract: The authors conducted a retrospective analysis of 1178 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. The minimum follow-up time was 3 years. The 10-year actuarial pelvic failure rate in Stage IB was 6% for tumors less than 3 cm, 15% for tumors 3 to 5 cm, and 30% for tumors more than 5 cm (P = 0.0018). The 10-year actuarial pelvic failure rate in Stage IIA was 10% for tumors less than 3 cm, 28% for tumors 3 to 5 cm, and 20% for tumors more than 5 cm (P = 0.09). Stage IIB unilateral nonbulky tumors (less than 5 cm) had a 20% pelvic failure rate compared with 28% for bilateral lesions and 35% for unilateral bulky tumors (more than 5 cm) (P = 0.35). In Stage IIB, pelvic failures were greater when disease extended into the lateral parametrium (30%) compared with medial parametrial involvement only (17%) (P = 0.01). In Stage III unilateral nonbulky tumors, the pelvic failure rate was 28% compared with 45% to 50% for unilateral bulky lesions (P = 0.002). Bilateral parametrial disease in Stage IIB did not increase the pelvic failure rate (21% in both subgroups) (P = 0.83), whereas in Stage III, bilateral parametrial involvement was associated with a 48% pelvic failure rate versus 28% for unilateral extension (P less than or equal to 0.01). Five-year disease-free survival (DFS) rates for IB tumors less than or equal to 3 cm was 90% versus 67% for tumors more than 3 cm (P = 0.01). In Stage IIA tumors less than or equal to 3 cm, 5-year DFS was 70% versus 45% for tumors more than 3 cm. Patients with Stage IIB nonbulky tumors (less than or equal to 5 cm in diameter) had better 10-year DFS (65% to 70%) compared with those with bilateral bulky tumors (45% to 55%) (P = 0.10). Stage III patients with unilateral nonbulky tumors had a 55% 10-year DFS compared with 35% to 40% for bulky tumors or bilateral parametrial involvement (P = 0.002). The authors concluded that clinical stage and size of tumor are critical factors in the prognosis, therapy selection, and evaluation of results in carcinoma of the uterine cervix.

Boron neutron capture therapy for cancer. Realities and prospects.

Abstract: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10 (10B), is irradiated with low-energy thermal neutrons (nth) to yield (4He) alpha-particles and 7Li nuclei (10B+nth-->[11B]-->4He+7Li+2.31 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of 10B and nth to individual cancer cells to sustain a lethal 10B(n, alpha) 7Li reaction. The current review covered the radiobiologic considerations on which BNCT is based, including a brief discussion of microdosimetry and normal tissue tolerance. The development of tumor-localizing boron compounds was discussed, including the sulfhydryl-containing polyhedral borane, sodium borocaptate (Na2B12H11SH), and boronophenylalanine (BPA), both of which are currently being used clinically in Japan as capture agents for malignant brain tumors and melanomas, respectively. Compounds currently under evaluation, such as boronated porphyrins, nucleosides, liposomes, and monoclonal antibodies (MoAbs), were also considered. Nuclear reactors have been used as the exclusive source of neutrons for BNCT. The use of low-energy (0.025 eV) thermal neutrons and higher-energy (1-10,000 eV) epithermal beams, beam optimization, and possible alternative neutron sources (accelerators) were also discussed. Clinical studies performed in the United States during the 1950s and 1960s for the treatment of malignant brain tumors were reviewed. Current studies in Japan and future studies in Europe and the United States concerning the treatment of glioblastomas and melanomas by BNCT were discussed, as were critical issues that must be addressed if BNCT is ever to be a useful therapeutic modality.

Survival, prognosis, and therapeutic response in osteogenic sarcoma. The Memorial Hospital experience.

Abstract: Two hundred seventy-nine consecutive patients with Stage II osteogenic sarcoma of the appendicular skeleton treated between 1976 and 1986 were studied to identify predictors of long-term survival. Survival was 77% and 73% at 5 and 10 years, respectively, with continuously disease-free survival being 70% and 69%. On univariate analysis, the most significant predictors of survival were the location of the primary lesion, local control of the tumor, and the degree of necrosis in the primary tumor after intravenous neoadjuvant chemotherapy (histologic response). On initial multivariate analysis, similarly, only location and histologic response to chemotherapy predicted disease-free outcome. After statistical control for local recurrence, only histologic response to chemotherapy was retained as an independent predictor, suggesting that in this data set, the location of primary lesion exerted its effect only secondarily through its association with the ability to provide local control. The risk of local recurrence was almost fivefold higher in tumors of the femur than in tumors of other locations (relative risk, 4.6) and, within the femur, was more than threefold higher in the proximal femur than in the distal femur (relative risk, 3.4). None of the other primary tumor or patient characteristics studied yielded independent predictive significance for survival. The rate of failure was almost fivefold as high in those with an incomplete response to chemotherapy compared with those with a complete response to chemotherapy (relative risk, 4.9; 95% confidence interval, 2.2 to 11). Even in those patients with minimal or no necrosis in the primary tumor, ultimately 62% and 54% were disease-free at 5 and 10 years, respectively.

Multiple cancers in the prostate. Morphologic features of clinically recognized versus incidental tumors.

Abstract: Multiple independent tumors were identified in specimens from 117 of 234 prostatectomies for clinical adenocarcinoma; there were 266 incidental cancers in these 117 prostates. The clinically detected carcinoma was the largest (or only) tumor in all 202 Stage B cases. However, among 32 Stage A cases (detection by transurethral resection), there were 8 prostates in which an incidental tumor was larger than the clinically manifest cancer. These were all small tumors except for two incidental cancers with a volume greater than 2cm3; roughly 80% of incidental carcinomas were smaller than 0.5 cm3, whereas fewer than 20% of manifest tumors were smaller than 0.5 cm3. Comparison with a series of cancers found incidentally at cystoprostatectomy for bladder cancer showed the same volume distribution as incidental (smaller) carcinomas in patients with prostate cancer. This distribution was thought to reflect the volume distribution of prostate cancer in the general population older than 50 years of age. It was concluded that additional incidental tumors are common in patients with prostate cancer, but their sum of volumes is seldom as large as the clinical cancer volume.

Immunohistochemical identification of tissue factor in solid tumors.

Abstract: Patients with cancer experience a much higher than expected incidence of thromboembolic disorders, commonly referred as Trousseau syndrome. Although this association has been well documented, the etiology of the hypercoagulable state is not known. The expression on tumor cells of tissue factor (TF), a membrane-bound lipoprotein that functions as a cofactor to factor VIIa in the initiation of the extrinsic pathway of blood coagulation, has been postulated as a possible mechanism. Whereas the distribution of TF in normal tissues is known, no large survey of TF expression in malignant tissues has been reported. In this study a polyclonal, monospecific rabbit anti-human TF IgG was used for immunohistochemical localization of TF antigen in 85 different tumor specimens. In general, cell types which normally express TF continued to do so after malignant transformation (41 of 60 epithelial tumor specimens were positive for TF). Tumors of nonepithelial origin frequently lacked TF, with only 3 of 19 specimens containing evidence of TF antigen. In addition five of six benign tumors did not express TF. Many tumor types commonly associated with Trousseau syndrome, for example lung, pancreatic, breast, colon and gastric carcinomas, stained positively for TF. Based on this survey, it appears that TF expression by tumors may be an important factor in the pathogenesis of a hypercoagulable state in some patients with cancer.

Variables correlated with the risk of lymph node metastasis in early rectal cancer

Abstract: To ascertain the risk of lymph node metastasis (LNM) from early rectal cancer, the authors retrospectively analyzed 154 patients with pT1 or pT2 rectal cancer treated by radical resection. Gross and microscopic pathologic characteristics of the primary tumor were examined as predictors of LNM. Comparisons were done by Fisher's test; significance was defined as a P value of less than 0.05. The incidence of LNM for T1 and T2 tumors was 3 of 26 (12%) and 28 of 128 (22%), respectively. LNM occurred significantly less often in well-differentiated cancers (0 of 12, 0%). The incidence of LNM for T1/T2 tumors without lymphatic vessel invasion (LVI) or blood vessel invasion (BVI) (20 of 119, 17%) was significantly less than that for T1/T2 tumors with LVI or BVI (10 of 32,31%). None of the T1 tumors without LVI or BVI had LNM. There was a trend toward decreased LNM for sessile nonulcerated tumors compared with nonpolypoid, exophytic, or ulcerated lesions (P = 0.06). Tumor size and colloid histologic characteristics were not significant predictive features for LNM. The data suggest that local excision alone is adequate for well-differentiated or moderately differentiated T1 rectal cancer in the absence of LVI or BVI and for well-differentiated T2 tumors. Radical resection or local excision combined with pelvic radiation therapy may be more appropriate for the remainder of early cancers.

Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma.

Abstract: Determinants of 5-year survival were evaluated after complete resection of pulmonary metastases from adult soft-tissue sarcomas Fifty-eight patients had complete resection (median survival 25 months, P = 00002), with a 258% absolute 5-year survival (15 of 58 patients); six patients had unresectable disease (median survival 6 months) and were excluded from additional analysis Eleven patients remain disease free, with a median follow-up of 76 months Significant independent prognostic indicators associated with improved survival (P less than 005) included metastasis doubling time of 40 days or greater (median survival 37 months versus 15 months if less than 40 days); unilateral disease on preoperative radiography (33 months versus 15 months if bilateral disease); three or fewer nodules on preoperative computed tomography (40 months versus 14 months if 4 or more nodules); two nodules or fewer resected (40 months versus 17 months if 3 or more nodules resected), and tumor histology (33 months for malignant fibrous histiocytoma versus 17 months for all others) Multivariate analysis identified the number of nodules detected by computed tomography preoperatively as having significant prognostic value

Impact of cyclophosphamide on long‐term reduction in sperm count in men treated with combination chemotherapy for ewing and soft tissue sarcomas

Abstract: Background. Treatment of cancer with multiple-drug chemotherapy regimens or radiation therapy can cause either temporary azoospermia of various durations or permanent azoospermia in young men. Methods. To identify which drugs in which doses contribute to long-term or permanent azoospermia, semen analyses were done on patients with Ewing and soft tissue sarcomas before, during, and after treatment with either CYADIC (cyclophosphamide, doxorubicin, and dacarbazine), or CYVADIC (vincristine added to CYADIC). Some patients also received other drugs or radiation therapy. Results. From pretreatment levels that were similar to those of control subjects, sperm production declined to azoospermia within 4 months of treatment. Sperm production returned in some patients after treatment; 40% of men recovered to normospermic levels by 5 years after treatment. Few patients showed continued recovery of sperm production after that time. The cumulative dose of cyclophosphamide was the most significant determinant of recovery to normospermic levels; approximately 70% of those who had received doses less than 7.5 g/m2 (median, 4.1 g/m2) recovered, but only 10% recovered when doses exceeded 7.5 g/m2. Conclusions. Thus, a risk of permanent sterility is associated with the use of the CYADIC and CYVADIC regimens in young men, especially when the cumulative dose of cyclophosphamide is greater than 7.5 mg/m2.

A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer.

Abstract: To decrease the toxicity of hepatic arterial fluorodeoxyuridine (FUDR) administered through an Infusaid pump (Shiley Infusaid, Inc., Norwood, MA), 50 patients with liver metastases from colorectal cancer were selected randomly to receive FUDR, 0.3 mg/kg/d, for 14 of 28 days, with or without a total dose of 20 mg of hepatic arterial dexamethasone for 14 of 28 days. Patients were stratified according to the percentage of liver involvement by tumor and the perfusion pattern on macroaggrated albumin perfusion scan (MAA) scan. There was a trend toward decreased frequency of bilirubin levels in the group receiving dexamethasone plus FUDR versus the group receiving FUDR alone (9% and 30%, respectively, had a 200% or greater increase from baseline; P = 0.07). Patients in the group treated with dexamethasone and FUDR received higher doses of FUDR in the second, third, fifth, and sixth months than those receiving FUDR alone; however, this was statistically significant only in the fifth month (percentages of planned dose received: 42% and 19%, respectively; P = 0.05), and there was no overall difference for the total 6-month period. The complete and partial response rates were increased in patients receiving dexamethasone and FUDR versus FUDR alone (8% and 63% versus 4% and 36%, respectively; P = 0.03), and there was a trend toward increased survival with the addition of dexamethasone (median, 23 months and 15 months, respectively; P = 0.06). In conclusion, the use of hepatic arterial dexamethasone is associated with an increased response rate and a trend toward increased survival and decreased bilirubin levels. Therefore, the authors recommend additional investigation of the use of dexamethasone with chemotherapy to treat hepatic metastases.

Feasibility of breast-conservation surgery after induction chemotherapy for locally advanced breast carcinoma.

Abstract: To determine whether preoperative chemotherapy sufficiently downstages disease in patients with locally advanced breast cancer to allow breast-conservation surgery, the clinical, mammographic, and histologic responses were analyzed after three cycles of preoperative vincristine, doxorubicin, cyclophosphamide, and prednisone that were administered to 143 patients with 1988 American Joint Committee on Cancer Stage IIB (17%), IIIA (36%), or IIIB (41%) disease or positive supraclavicular lymph nodes (6%) who had a complete (16%) or partial (84%) clinical response and underwent total mastectomy and axillary node dissection. Thirty-three (23%) were potential breast-conservation candidates based on criteria of complete resolution of skin edema, residual tumor size less than 5 cm, and absence of known tumor multicentricity or extensive intramammary lymphatic invasion. Of these 33, the initial tumor size decreased from a median of 5 cm to less than 1 cm, with 42% having no residual tumor in the mastectomy specimen and 45% having negative nodes. No tumor was found in any other quadrant of the breast, and no patient had a recurrence in the chest wall. After a median follow-up of 34 months, only three patients had distant metastases; two of these died of disease.