Showing papers in "Cancer in 1975"

A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival

Abstract: The presenting clinical features of 71 patients with multiple myeloma were correlated with myeloma cell mass (myeloma cells X 10(12)/m2 of body surface area) determined from measurements of monoclonal immunoglobulin (M-component) synthesis and metabolism. Bivariate correlation and multivariate regression analyses showed that myeloma cell mass could be accurately predicted from A) extent of bone lesions, B) hemoglobin level, C) serum calcium level, and D) M-component levels in serum and urine. Analyses of response to chemotherapy and survival indicated significant correlation with measured myeloma cell burden. The results were synthesized to produce a very reliable and useful clinical staging system with three tumor cell mass levels (Table 7). For clinical research purposes, multivariate regression equations were developed to predict optimally the exact myeloma cell mass. Thus, initial staging can be quantitatively related to followup using tumor cell mass changes calculated from changes in M-component production. Use of the clinical staging system sould provide better initial assessment and followup of individual patients, and should lead to improved study design and analysis in large clinical trials of therapy for multiple myeloma.

The evolution of cancer of the colon and rectum.

Abstract: The malignant potential of adenomas of the colon and rectum varies with size, histological type and grade of epithelial atypia. The adenomatous polyp is usually small and has a low malignant potential, whereas tumors with a villous structure are usually larger and have a much higher cancer rate. Severe atypia is more common in villous adenomas than in adenomatous polyps. Evidence is presented which suggests that most cancers of the colon and rectum have evolved through the polyp-cancer sequence although the majority of adenomas do not becoma cancerous during a normal adult life span. The slow evolution of the polyp-cancer sequence is stressed. The implications of the polyp-cancer sequence for the design of cancer prevention programmes and the study of the aetiology of large bowel cancer are discussed.

Carcinoid Tumors An analysis of 2837 cases

Abstract: Two thousand eight hundred thirty-seven cases of carcinoid tumor from files at the National Cancer Institute were analyzed statistically. Tumors were found in the lung, ovary, and biliary and gastrointestinal tracts. Most were in the appendix, rectum, and ileum. Age-adjusted incidence rates were higher for black males, except for lung carcinoids. Carcinoids showed several differences from other kinds of tumor, including a low age for appendiceal and lung cases and low male/female and black/white ratios in the lung. Percentages of concurrent neoplasms and multiple carcinoids were low compared to other series. Five-year relative survival rates ranged from 99% (appendix) to 33% (sigmoid colon). Survival for colon cases was not so low as expected on the basis of the high rate of metastasis. Some appendiceal carcinoids were metastatic and may have killed 1 patient. Findings are compared with other studies.

The pathology of invasive breast cancer. A syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol no. 4).

Abstract: The inter-relationships of 32 pathologic and 7 clinical parameters encountered in the study of 1000 examples of invasive breast carcinoma have been presented. In some instances the biological significance of these associations is at present unclear. In others it is to be noted that there is no information provided as to the rank of their significance. Nevertheless, the associations that were encountered not only help further characterize the various forms of breast cancer but also provide information regarding the possible biological significance of some of their features. Although it is not our intention to minimize the possible significance of the inter-relationships of pathologic parameters, most emphasis in the summarizing statements which follow has been placed upon those correlations which may relate to prognosis. In this regard reference has been made to short-term treatment failure, vis a vis local recurrence and/or metastases, which may not necessarily accurately reflect patient survival, although generally such a relationship exists. Information in this regard as well as to the rank of the significance of these pathologic features shall be forthcoming when sufficient time has elapsed since the inception of this study to allow for such conclusions, i.e. survival or long-term treatment failure rates. Lastly, it becomes evident that the guidelines followed in the examination of these specimens appear to represent at least the minimum requirements necessary for a meaningful pathologic evaluation of breast carcinoma.

Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP

Abstract: This paper reports the preliminary results of a controlled study randomizing MOPP vs. a new four-drug combination (ABVD) in advanced Hodgkin's disease. ABVD consists of 6 cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide. The purpose for designing this new combination was two-fold: to compare the efficacy of ABVD with MOPP, and to demonstrate absence of cross-resistance between the two regimens. Of 60 patients entered into the study, 45 (MOPP25, ABVD20) are presently evaluable for the analysis of remission induction. No patient was previously treated with chemotherapy; 20% had relapsed after primary radiotherapy. Whenever possible, complete remission was defined also through rebiopsy of known organ involvement. Complete remission occurred in 76% of patients treated with MOPP and in 75% of those given ABVD, with no difference between the two regimens as far as stage (IIIB-IIIS and IV), histologic type, and prior irradiation were concerned. Crossover carried out for progressive disease or for relapse after initial remission showed absence of cross-resistance between MOPP and ABVD. Toxic manifestations after ABVD were in general well tolerated and reversible. The percent of optimal dose for each drug was as follows: adriamycin 87%, vinblastine 87%, bleomycin 96%, and imidazole carboxamide 96%. These preliminary results indicate that in terms of complete remission, ABVD could represent a successful alternative to MOPP to be used either in MOPP failures or in sequential combination with MOPP. However, the lack of long-term followup limits at the present time an adequate comparison between the two treatments.

Malignant soft tissue tumors of probable histiocytic origin (malignant fibrous histiocytomas): general considerations and electron microscopic and tissue culture studies.

Abstract: Correlated light and electron microscopic study of four fibrous histiocytomas of proven malignancy has confirmed the presence of histiocyte-like and fibroblast-like cells in this tumor. In addition, an undifferentiated cell type, giant cells, xanthomatous cells, and rare cells with morphological characteristics intermediate between those of histiocytes and fibroblasts were seen. "Nuclear body" type inclusions were commonly present in both principal cell types in all four cases, as were the somewhat less common cytoplasmic inclusion bodies. Electron microscopic study of a tissue culture of one of these tumors demonstrated only fibroblast-like, histiocyte-like, and xanthomatous cells. The possibility is suggested that both principal cell types in this tumor may derive from the same undifferentiated stem cell.

The central nervous system in childhood leukemia. II. Subacute leukoencephalopathy

Abstract: A study was performed to evaluate the clinical and histopathologic characteristics of a distinctive degenerative lesion within the central nervous system (CNS) of children with acute lymphocytic leukemia (ALL). Of the 231 patients in this study, 13 were found to have specific degenerative changes in telencephalic white matter. Morphologically, the principal changes consisted of diffuse reactive astrocytosis and multiple, noninflammatory necrotic foci, often containing varying amounts of mineralized cellular debris. Clinical features common to all patients with this leukoencephalopathy were: 1) cranial irradiation of 2000 rads or more and 2) methotrexate administered systemically after irradiation. Comparison of selected clinical features of patients with and without leukoencephalopathy showed that methotrexate administered intravenously after a cumulative dose of CNS irradiation of 2000 rads or more can result in degeneration of CNS white matter in patients with ALL. Age at time of irradiation, bacterial infections, nutrition, and CNS leukemia were not causally related to the development of this disease. This study suggests that chemotherapeutic agents may diffuse through the blood-brain barrier following CNS irradiation of 2000 rads or more.

Extraskeletal neoplasm resembling Ewing's sarcoma

Abstract: This article reviews the pathologic features and the behavior of 39 small, round, or oval cell sarcomas occurring in the soft tissues and considered histologically indistinguishable from Ewing's sarcoma of bone. The tumors affected chiefly young adults (median age 20 years) and most commonly involved the soft tissues of the lower extremity and the paravertebral region. Microscopically, they consisted of solidly packed small, round, or ovoid cells of great uniformity, arranged in sheets or lobules separated by strands of fibrous connective tissue. The nucleus of the tumor cells contained finely divided chromatin, a distinct nuclear membrane, and frequently a minute nucleolus. The scanty ill-defined cytoplasm contained varying amounts of glycogen. Sometimes the histologic picture was dominated by a "peritheliomatous" pattern, or by large areas of necrosis or hemorrhage. Followup data ranging from 1 month to 14 years were available in 35 of the 39 cases (93%). Of these, 13 were alive and 22 had died. In the majority of the fatal cases, the clinical course was rapid; metastatic lesions developed within a few months after the primary tumor was excised. The lungs and the skeleton were the two most common sites of metastasis. Cure may be achieved by wide local excision of the tumor at an early stage of the disease, combined with radiation therapy and chemotherapy.

Medullary carcinoma of the thyroid gland.

Abstract: One hundred thirty-nine surgically treated patients with medullary carcinoma of the thyroid gland (MTC) were seen in our institution between January, 1926 and December, 1973. The incidence of this tumor among all thyroid cancers was 8%. Twenty-nine patients had the familial form of MTC; they were subclassified, on the basis of the phenotype, into a group of 15 patients with Sipple syndrome (or multiple endocrine neoplasia (MEN) Type 2A) and a group of 14 patients with mucosal-neuroma phenotype (or MEN type 2B). Better survivorship was seen in the younger patients, in those with bilateral tumors, in familial MTC, and in patients whose tumor was confined to the thyroid gland at the initial surgery. The incidence of tumor recurrence was 34%. However, in those with adequate surgical treatment, the recurrence was only 23%. The 5- and 10-year survivorships were 80% and 67%, respectively. The best chance of cure lies in early diagnosis through the use of immunoreactive calcitonin measurement in family members at risk, and an aggressive surgical attack on the primary tumor and any cervical metastases.

Comparison of continuously infused 5-fluorouracil with bolus injection in treatment of patients with colorectal adenocarcinoma

Abstract: In a randomized series of 70 patients with with colo rectal adenocarcinoma, a comparison of systemic 5-fluorouracil chemotherapy administered as a continuous 120-hours infusion vs. intravenous bolus injection daily for 5 days demonstrated superiority of prolonged intravenous infusion. The most striking advantage of prolonged infusion of 5-FU was the absence of myelotoxicity. Fifteen of the 34 patients treated with infusion and 8 of the 36 patients treated by bolus injection developed objective tumor responses. The difference in response rate at least in part is explainable by unequal distribution of patients with different characteristics between the two treatment groups.

Combination versus single agent chemotherapy: a review of the basis for selection of drug treatment of cancer.

Abstract: In a period of a little over 20 years, chemotherapy of cancer has evolved from a period of empiricism with little impact on the cancer problem to become part of a sound medical discipline with firm scientific underpinning playing an increasingly important role in the control of cancer. This progress has come from an increasing knowledge of cancer biology and pharmacology and the application of this knowledge to improved design of clinical trials, with due consideration to the intricacies of the natural history of each disease in question. Now that the chemotherapeutic tools are sharpened, their use in combinations with other modalities in the previously unfamiliar setting of the patient with early stages of the disease promises to lead to an even more exciting chapter in clinical cancer research in the next decade.

Disseminated necrotizing leukoencephalopathy: A complication of treated central nervous system leukemia and lymphoma

Abstract: This report describes a form of disseminated necrotizing leukoencephalopathy that has been observed in four children with acute lymphoblastic leukemia, and one child with Burkitt's lymphoma terminating in a leukemic phase. In addition to systemic vincristine, cytosine arabinoside, cyclophosphamide, and steroids, these patients received courses of intrathecal methotrexate, cytosine arabinoside, and hydrocortisone, because of meningeal tumor cell infiltration. Whole brain radiation was also given either before or during intrathecal therapy. Three of the children had a progressive irreversible neurologic illness, which developed either at or shortly after the completion of combined triple intrathecal therapy, death ensuing approximately 2 months later. The neuro-pathologic lesions consisted of discrete multifocal necroses of coagulative type, apparently extending by confluence, and disseminated in the cerebral white matter in a random manner. In one case, extensive symmetrical demyelinating and necrotizing lesions involved the centrum ovale bilaterally. There was a remarkable absence of inflammatory cellular response and a relative paucity of macrophage reaction, with usually little or no tissue breakdown. In addition to demyelination and glial cell loss, there was striking axonal damage, with conspicuous axonal swellings both within and around the necrotizing lesions. The surrounding white matter showed focal status spongiosus and a moderate astrocytic response. Vascular fibrinoid necrosis was inconstant and, except in one case, rarely observed. The possible causal relationship of these lesions to combined triple intrathecal antimetabolite therapy and brain radiation is discussed.

Leukoplakia revisited. A clinicopathologic study 3256 oral leukoplakias.

Abstract: During a 13-year period, 3256 specimens clinically diagnosed as leukoplakia “keratosis,” “white patch”) were submitted to the oral pathology laboratories of Indiana University School of Dentistry and Emory University School of Dentistry. These comprised 6.2% of the tissue specimens processed by these laboratories. The cases were analyzed as to age of occurrence, site of involvement, and pathologic findings. It was found that: leukoplakia occurs chiefly in the 5th, 6th, and 7th decades; about half of the lesions involved the mandibular mucosa, mandibular sulcus, and buccal mucosa; leukoplakia was slightly more common in men (54.2%). Microscopic study showed that 80.1% of the leukoplakias were varying combinations of hyperorthokeratosis, hyperparakeratosis, and acanthosis without evidence of epithelial dysplasia. Mild to moderate epithelial dysplasia was noted in 12.2% of specimens, and severe epithelial dysplasia or carcinoma in situ was found in 4.5%. Infiltrating squamous cell carcinoma was diagnosed in 3.1% of specimens submitted with a clinical diagnosis of leukoplakia. The risk of epithelial dysplasia, carcinoma in situ, or carcinoma varied between the anatomical locations of leukoplakia. The incidence of epithelial alteration, ranging from dysplasia to carcinoma, was 42.9% for lesions of the floor of the mouth, 24.2% for tongue lesions, and 24.0% for lip leukoplakias. The incidence of similar epithelial alterations in other sites varied from 18.8% for palatal lesions to 11.7% for leukoplakias of the retromolar area. The data suggest that there are regional differences in the incidence and character of leukoplakia in the United States. The Emory material, obtained almost exclusively from patients residing in the Southeastern United States, showed a proportionately higher total incidence, a lower male/female ratio, and a greater frequency of epithelial dysplasia, particularly in females, than the Indiana material, which came almost entirely from residents in the Northcentral United States.

Spindle cell lipoma.

Abstract: Spindle cell lipoma is a specific type of lipoma that is easily mistaken for a liposarcoma. An analysis of 114 cases of this tumor from the files of the Armed Forces Institute of Pathology reveals that is occurs chiefly in male patients between 45 and 70 years of age and affects the regions of the shoulder and posterior neck almost exclusively. Microscopically, it consists of an intricate mixture of lipocytes and uniform spindle cells within a matrix of mucinous material traversed by a varying number of birefringent collagen fibers. Ultrastructural studies in one case support the fibroblastic nature of the spindle cells. Followup information obtained in 63 patients with this lesion revealed a uniformly favorable clinical course, indicating that local excision is the treatment of choice, and that there is no need or reason for radical surgical procedures.

Hemangiopericytoma. A clinicopathologic study and long-term followup of 60 patients.

Abstract: The clinical courses of 60 patients with hemangiopericytoma of the somatic soft tissues are summarized in this retrospective study. The tumors were subjected to a comparative histologic review and classified as benign (12 lesions), borderline malignant (16 lesions), and malignant (32 lesions). Tumors with 1 mitotic figure per 10 high-power field and moderate cellular anaplasia or 1 mitotic figure per 20 high-power fields and moderate cellular anaplasia may be expected to follow a malignant clinical course. Six of the 16 tumors with these microscopic features (borederline lesions) metastasized (37.5%), and 6 exhibited local recurrences after excision. Of the 32 malignant tumors, 25 (78%) metastasized. Twenty-three patients with malignant tumors were followed for more than 5 years or until death from tumor, and only one patient was alive and free of disease. Fifteen of the 23 patients experienced one of more local recurrences. None of the benign tumors metastasized. Surgical ablation of hemangiopericytioma is, in our experience, the only satisfactory method of treatment. Amputation of an extremity need be done only when the location of the lesion precludes a wide local excision. Local recurrent tumor was experienced by 22 patients after an inadequate local excision. Long-term follow-up is recommended because metastasis became apparent in 11% of patients with malignant tumors and 7% with borderline tumors after 5 "disease-free" years.

Concepts for systemic treatment of micrometastases

Abstract: If total tumor cell kill is a requirement for "cure," as it probably is for at least some tumors, treatment of micrometastases containing less than or equal to 10-6 viable tumor cells is a problem facing all cancer therapists. Metastatic tumor cell foci of less than or equal to 10-6 cells, particularly if widely disseminated, are, in the main, grossly undetectable and are, therefore, the proper targets for the chemotherapist and the immunotherapist. Current knowledge of tumor cell population growth kinetics indicates that the growth fraction (viable cells undergoing active cell replication) is inversely related to population size. Micrometastases should, therefore, be more sensitive to antimetabolite (cell-cycle-specific) anticancer drugs than the larger, grossly apparent, primary tumor from which they were derived. In fact, drug response of the primarytumor may not reliably predict the sensitivity of micrometastases to cell-cycle-specific drugs. In addition, optimal drug treatment scheduling for effective, but noncurative, drugs against clinically recognized tumors may not predict optimal scheduling of the same drugs against micrometastases. This is shown particularly in cell-cycle-specific drugs, since the generation time of tumor cells in small population foci (less than 10-7 cells) is often significantly shorter than in larger population foci (greater than 10-7 cells). Since first-order cell kill kinetics characterizes effective drug kill of tumor cells and the best currently known anticancer drugs have variable but generally limited tumor cell kill potential, drug treatment of likely micrometastases should be started as soon after the end of likely noncurative radiologic or surgical treatment as possible. Experimental data indicating that significantly smaller numbers of viable tumor cells can establish lethal tumors in the presence of radiation-inactivated tumor cells than in their absence suggest that small populations of residual viable tumor cells in radiation-treated tumor sites may be a greater threat to clinical cure than similar sized populations remaining in situ after surgery. Experimental data supporting the above concepts are presented and discussed.

Malignant histiocytosis (histiocytic medullary reticulosis). I. Clinicopathologic study of 29 cases

Abstract: The clinical records and histologic materials from 29 cases of malignant histiocytosis (MH) have been reviewed, as well as autopsy findings in 14 cases. The mean age was 31 years, with a 2.2:1 male to female preponderance. Major physical findings included temperature elevation, lymphadenopathy, hepatomegaly, splenomegaly, and preterminal jaundice. Common laboratory findings were anemia, leukopenia, and thrombocytopenia. The median survival was 6 months, the mean 14 months, and the range from 1 month to 8 years. The histologic features observed in lymph nodes, liver, spleen, and bone marrow have been emphasized, as well as features useful in differential diagnosis. In contrast to our experience with the non-Hodgkin's lymphomas, bone marrow aspiration was superior to biopsy in assessing marrow involvement. Unusual manifestations included soft tissue infiltration in 5 cases; 2 of these patients presented with a soft tissue mass. The distinctive clinical as well as histologic findings warrant recognition and separation of MH from other hematopoietic disorders.

Aggressive growth and neoplastic potential of odontogenic cysts. With special reference to central epidermoid and mucoepidermoid carcinomas

Abstract: An aggressive form of odontogenic cyst known as the keratocyst has been reviewed with a report on the findings of 70 new instances. Recurrence after 2 years of followup was found to be 20%. From both a review of the literature and original cases, carcinomatous and ameloblastomatous transformation in odontogenic keratocysts seems to be an extremely rare phenomenon. Alternatively, epidermoid carcinoma and mucoepidermoid carcinoma arising centrally within the jaws are often associated with other types of dental cycts. Review of 36 instances of central epidermoid carcinoma has disclosed that 75% were associated with a cyst lining; the 2-year survival rate was found to be 53%. Central mucoepidermoid carcinoma was associated with a dental cyst or impacted tooth in 48% of the cases, and enjoyed a 100% 2-year and 5-year survival; however, 2 patients were recorded alive with disease at 4 months and 10 years, whereas another patient succumbed to disease 14 years postoperatively.

Sarcoma of soft tissue: clinical and histopathologic parameters and response to treatment.

Abstract: Radical dose radiation therapy alone or combined with limited surgery has been employed in the management of 100 patients with primary (71) and recurrent (29) sarcoma of soft tissue. Results of this experience show that a combination of conservative surgery and radiation therapy, based upon radical dose levels and sophisticated techniques, is effective: only 13 of 100 patients showed local regrowth during a followup of 2-12 years. This may be compared with an expected congruent to 25 recurrences had treatment been radical surgery (wide resection or amputation). For lesions located on the distal extremities (elbow-hand, knee-foot) there were local failures in only 3 of 59 (5 percent). Further, 75 percent of patients treated by the improved techniques utilized in the recent 8 years retained a useful limb which is free of pain or edema. Histopathologic grade is demonstrated to be an important indicator of prognosis of local recurrence and of disease-free survival. Local recurrence rates were 0/23, 9/53, and 4/24 for Grades 1, 2, and 3. Disease-free survival rates were 19/23 (86 percent), 27/53 (51 percent), and 4/24 (17 percent) for Grades 1, 2, and 3, respectively. Invasion of skin appeared to be a sign of poor prognosis; 8 of 9 such patients developed distant metastases.

Radiation tolerance of the spinal cord.

Abstract: A series of nine cases of radiation myelopathy seen at the University of California, San Francisco (UCSF) is reviewed, and their treatment data converted into nominal single doses (NSD) and equivalent single doses (ED). The 1% incidence level of myelopathy in the thoracic cord is 1015 rets (ED), and the 50% incidence level is 1476rets (ED). Caution should be used when utilizing a rapid fractionation schedule; it appears that 2000 rads in 5 fractions and 3000 rads in 10 fractions is a safe regimen for the thoracic spinal cord.

Modification of radiation injury to normal tissues by chemotherapeutic agents

Abstract: The effects of several cancer chemotherapeutic agents on radiation damage to normal intestine, esophagus, and lung tissue were evaluated in LAF 1 mice using quantitative endpoints. In all tissues tested, actinomycin D increased injury and BCNU did not. In the intestine, adriamycin enhanced radiation damage more than any other agent. Bleomycin increased damage in the esophagus but not in the lung or intestine. Cyclophosphamide increased injury only in the lung, where vincristine caused minimal injury, and hydroxyurea, none. Only prednisolone caused significant radioprotection when given at the time of irradiation or at the time of expected death from pulmonary injury.

"Residual" mammary carcinoma following simulated partial mastectomy.

Abstract: Treatment of mammary carcinoma by partial mastectomy rather than by total mastectomy and axillary dissection may diminish the chances of long-term cure by risking incomplete removal of all local carcinoma at the initial operation. This study was undertaken to determine by pathologic examination how often carcinoma might remain in the breast and axilla after partial mastectomy. The operation was simulated in 203 mastectomy specimens after operations for unilateral invasive carcinoma. In so far as could be determined on gross examination, the entire primary lesion was included in the quadrant which was excised in the simulated procedure. Among 100 women with primary lesions less than 2 cm in diameter, 26% had carcinoma in the breast which remained after simulated partial mastectomy. Six percent of them also had axillary node metastases. An additional 30% only had axillary node metastases. When the primary lesion was more than 2 cm in diameter, 38% of patients had carcinoma in the breast after simulated partial mastectomy, of whom 29% also had axillary metastases. After simulated partial mastectomy, carcinoma was found in 80% of breasts from patients with lesions in the subareolar area, in contrast with 25–35% of patients with a primary carcinoma in one of the four quadrants. None of the 9 patients with medullary and colloid carcinomas that measured under 2 cm had axillary metastases or carcinoma in the breast outside of the primary quadrant. The findings suggested that a familial history of breast carcinoma or a large primary lesion may be associated more often with multifocal disease, but factors such as age at diagnosis, axillary status, and the mammogram report did not have significant predictive value for distinguishing between patients who did or did not have carcinoma in breast tissue after the primary had been removed by a simulated partial mastectomy.

A clinicopathologic study of 92 cases of granulosa cell tumor of the ovary with special reference to the factors influencing prognosis.

Abstract: Ninety-two cases of granulosa cell tumor of the ovary have been studied. The clinical and pathologic data from this group were similar to that obtained in previous series. Because of the long natural history of many granulosa cell tumors, crude death rates over a relatively short period give little indication of the true malignant potential of these neoplasms and hence corrected survival rates were calculated; these show that, if no patient died from any other disease, approximately half of the women with this neoplasm would die, as a result of the tumor, within 20 years. Factors indicating a relatively poor survival rate were: age over 40 at the time of diagnosis, a presentation with abdominal symptoms, a palpable mass, a solid large tumor, bilateral tumors, extraovarian spread, and numerous mitotic figures in the tumor. It is suggested that all granulosa cell tumors should be considered as malignant and that the factors pointing to a poor prognosis are those indicating that a particular tumor has been diagnosed at a late stage in its natural history, either because it has been present for a long time or because it is highly malignant. There are no definite criteria for defining the prognosis in a case in which the tumor has been removed at any early stage in its natural life history.

Preoperative irradiation for carcinoma of the rectum and rectosigmoid colon: Report of a national veterans administration randomized study

Abstract: In 1964 the Veterans Administration Surgical Adjuvant Group (VASAG) initiated a large-scale, controlled, randomized protocol to study the role of low-dose preoperative irradiation (2000-2500 rads/10fractions/12 days) in patients with operable adenocarcinoma of the sigmoid colon and rectum. This report analyzes the data in 700 patients, all at 5-year risk. There appears to be a definate benefit to irradiated patients who undergo abdominoperineal resections, when compared with the controls. This advantage is reflected in improvement of 5-year survival, and reduction in lymph node invasion, local recurrence, and distant metastases. A second protocol has been initiated in 30 VA hospitals employing a higher dose (3150 rads) to extended portals (toL2) to male patients who require abdominoperineal resections.

Clinicopathologic review of 88 cases of carcinoma metastatic to the pituitary gland

Abstract: Clinical and pathologic features of 88 cases of carcinoma metastatic to the pituitary gland were reviewed. In 61 (69.3%), metastases were localized either in the posterior lobe alone or in the posterior and anterior lobes together; only 12 (13.6%) involved the anterior lobe alone. Diabetes insipidus was present in 6 patients (6.8%), one of whom also had clinical panhypopituitarism due to metastatic tumor and necrosis in the anterior pituitary lobe. Breast and lung were the most frequent primary sites in women and men, respectively. Sixty-four (72.7%) of these glands were grossly normal at necropsy. Metastases to the pituitary gland occur more frequently in the posterior lobe than in the anterior lobe, and my ve reflected clinically by diabetes insipidus in patients with diseminated carcinoma. Clinical panhypopituitarism is a rare accompaniment of anterior lobe involvement.

Geographic pathology of occult thyroid carcinomas.

Abstract: Thyroid glands obtained from patients in southeastern Canada, northeastern Japan, southern Poland, western Colombia, and from Japanese living in Hawaii were serially step-sectioned and examined microscopically using identical techniques and diagnostic criteria. The prevalence of occult papillary thyroid carcinoma was significantly higher in Japan (28.4%) and in Hawaiian Japanese (24.2%) when compared with Canada (6%), Poland (9.1%), and Colombia (5.6%). The carcinomas were all papillary except for a single follicular lesion from Colombia. There was no significant sex prevalence. Most of the patients were between 40 and 79 years of age, but there was no particular predominant decade. Only the Colombian series had a large number of younger patients, and they showed a slightly lower prevalence of occult carcinomas before age 40. Most papillary thyroid carcinomas grow slowly and probably remain occult for the life of the patient.

Risk of second tumors in survivors of childhood cancer

Abstract: A new malignancy was diagnosed in 19 of 414 long-term survivors of cancer in childhood. All but two lesions were attributable to prior radiotherapy; eight were successfully treated. Excluding 4 patients ascertained in connection with the second malignancy, there were 15 in the series who developed a new cancer, in contrast to 0.7 cases expected (p less than 0.001). The 20-year (5-24 years after initial diagnosis) cumulative probability of a second cancer was 12% (S.E. 4%), and the radiation-related cancer rate was 1.8 cases in exposed tissues per million person-years per rad. Host susceptibility may have had an etiologic role, but an oncogenic effect of chemotherapy was not demonstrable. Another 13 study patients developed benign tumors. These findings emphasize the importance of long-term surveillance of children with cancer.

Erythroplakia of the oral cavity

Abstract: Erythroplakia of the oral cavity is a specific disease entity which must be differentiated from other specific or nonspecific inflammatory oral lesions, although this can only be done in most cases by biopsy. A series of 58 cases of oral erythroplakia has been retrieved from 65,354 consecutively accessioned biopsy-surgical specimens. The disease was found to have no apparent sex predilection (31 males and 27 females) and was most frequently seen during the 6th and 7th decades. The most common site of occurrence in females was the mandibular alveolar mucosa-mandibular gingiva-mandibular sulcus, whereas this was the least common site in males. The floor of the mouth was the most common site in males, followed by the retromolar area in both males and females. The histologic findings emphasized the serious nature of the disease, since 91% of the specimens were either invasive carcinoma, carcinoma in situ, or severe epithelial dysplasia.

Abnormalities of taste sensation in cancer patients.

Abstract: In fifty patients with cancer, subjective and objective correlates of anorexia of malignancy were studied. Decreased taste was reported by 25patients, and an aversion for meat was reported by 16 patients. The decreased taste symptom correlated with an elevated taste threshold for sweet (sucrose), and the symptom of meat aversion correlated with a lowered taste threshold for bitter (urea). The likelihood of having a taste abnormality increased with increasing extent of disease, but not with histologic type of neoplasm. Patients with an abnormality of taste had an increased incidence of weight loss compared with patients with normal taste, even though many in the latter group had other causes of weight loss. These observations suggest that an abnormality of taste may be one determinant of the anorexia of malignancy. Better understanding of the anorexia in the cancer patient may contribute to the care of the patient.

Mesenchymal tumors of the uterus. V. Intravenous leiomyomatosis: A clinical and pathologic study of 14 cases

Abstract: Fourteen examples of intravenous leiomyomatosis in the FIP files were studied. Growth beyond the uterus occurred in 10 of the 14 examples, largely in vessels in the broad ligament and in uterine and iliac veins. Metastasis to the heart occurred in 1 example. The study provides evidence that is consistent with both theories of origin of intravenous leiomyomatosis; namely, that it may arise either from the wall of veins within the myometrium or be a result of unusually extensive vascular invasion from a leiomyoma of the myometrium. Intravenous leiomyomatosis should be distinguished from a leiomyoma with vascular invasion by arbitrarily limiting the designation of leiomyoma with vascular invasion to neoplasms in which the vascular growth is a microscopic finding and confined within the leiomyoma. Criteria are given for distinguishing intravenous leiomyomatosis from endometrial stromal sarcoma, leiomyosarcoma, leiomyoma with vascular invasion, and leiomyomatosis peritonealis disseminata.