Familial polyposis coli: the spectrum of ocular and other extracolonic manifestations.

Familial polyposis coli (FPC) is hereditary condition that conveys a virtual 100% risk for the development of colon cancer in the untreated patient. A total of 56 patients with FPC underwent complete ophthalmic examination. Highly pleomorphic pigmented retinal lesions were identified bilaterally in 52% (n = 29) and unilaterally in 14% (n = 8) of our subjects. In all, 33 patients had one or more extracolonic expressions associated with FPC, including desmoids, osteomas, epidermoid cysts, lipomas, fibromas, and upper gastrointestinal tract polyps. In 15 patients, pigmented fundus lesions were the only extracolonic manifestations. No significant association between eye findings and other extracolonic manifestations could be established. The presence or absence of pigmented fundus lesions was found to cluster within families. Pigmented fundus lesions are probably a variably penetrant expression of the polyposis gene and do not appear to be specifically associated with subgroups of inherited polyposis syndromes such as Gardner's syndrome.

Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis.

Over a 4-year period in a chemoprevention trial on large bowel neoplasia, 58 patients with familial adenomatous polyposis were treated with 4 g of ascorbic acid (vitamin C)/day plus 400 mg of alpha-tocopherol (vitamin E)/day alone or with a grain fiber supplement (22.5 g/day). In this randomized, double-blind, placebo-controlled study, we determined the effects of these supplements on rectal polyps in these patients. Analysis by intent to treat suggested that the high-fiber supplement had a limited effect. Analysis adjusted for patient compliance showed a stronger benefit from the high-fiber supplement during the middle 2 years of the trial. The results provide evidence for inhibition of benign large bowel neoplasia by grain fiber supplements in excess of 11 g/day in this study population. The findings are consistent with the hypothesis that dietary grain fiber and total dietary fat act as competing variables in the genesis of large bowel neoplasia.

Hyperpigmented lesions of the retinal pigment epithelium in familial adenomatous polyposis.

Ophthalmic examinations were performed on 56 patients with validated familial adenomatous polyposis (FAP) for hyperpigmented defects of the retinal pigment epithelium. Such lesions were seen bilaterally in 29 patients (52%) and unilaterally in 8 patients (14%). Of the 56 patients, 33 had one or more of the extracolonic expressions associated with Gardner syndrome. We found retinal lesions in 8 patients without any of the expressions of Gardner syndrome. No association was found between Gardner syndrome and the retinal lesions when these patients were compared to patients without any stigmata of Gardner syndrome, nor was any significant association found when each of the expressions was compared individually with the presence of the pigmented retinal lesions. The presence or absence of eye findings were seen to cluster within families. There was no association with sex. Fundus lesions are apparently a variable expression of the FAP gene and are not specifically associated with Gardner syndrome.

The use of indomethacin, sulindac, and tamoxifen for the treatment of desmoid tumors associated with familial polyposis.

Seven familial polyposis patients with desmoid tumors were treated with indomethacin, sulindac, or tamoxifen either as single agents or in combination. Serial computed tomographic (CT) scan examination was employed for objective measurement of tumor size since physical examination alone was an inaccurate means to evaluate intraabdominal and retroperitoneal desmoids. Only one patient with minimal tumor burden demonstrated a favorable response with complete resolution of an abdominal wall desmoid.

Upper gastrointestinal neoplasia in familial polyposis.

Upper gastrointestinal (UGI) endoscopy was performed in 41 asymptomatic American patients with familial polyposis to assess the prevalence of gastric and duodenal polyps and to characterize their pathological features. Eighteen patients (44%) had UGI endoscopic abnormalities. Six patients had both gastric and duodenal lesions. Eight patients had only gastric polyps, and four had duodenal polyps only. The presence of other extracolonic expressions of polyposis had a suggestive but statistically insignificant correlation with UGI polyps. Patients with familial polyposis and duodenal adenomatous polyps are at high risk for the development of periampullary cancer; screening and identification of these individuals is recommended.

Psychosocial adjustment of familial polyposis patients and participation in a chemoprevention trial.

Psychological and social adjustment was assessed in eighty-nine individuals with familial polyposis, a genetically transmitted disease placing one at high risk for colon cancer. Three illness-related concerns were identified: fear about future health due to the high risk for cancer; guilt about transmitting a genetic disease to one's children; and concern about physical disfigurement resulting from surgery. Well-being scores were generally positive, although somewhat lower than those reported in a community sample. Two factors in particular influenced well-being scores: those with higher levels of concern about disfigurement reported lower well-being, and those with accurate information about the disease reported higher well-being. Of the eighty-nine individuals included in this study, sixty-one were participating in a clinical trial and twenty-eight had been invited but declined entry. Demographic and psychosocial factors were examined for their relationship to participation. Only three of these variables, length of time since diagnosis, religious affiliation, and geographic location distinguished participants from nonparticipants.

The spectrum of polyposis.

Familial polyposis is a systemic defect of growth regulation. Extracolonic expressions are common and serious, about equal in risk to carcinoma of the large intestine. Periodic surveillance of the upper gastrointestinal tract is particularly important. More intensive surveillance of the large intestine may lead to better results in patients with polyposis who have carcinoma of the large intestine develop.

Pancreatoduodenectomy for resectable malignant periampullary tumors.

The results of all 53 pancreatoduodenectomies performed at one hospital were reviewed for operative mortality, accuracy of operative diagnosis and long term survival. Although carcinomas of the ampulla are much more rare than those of the pancreas, the number of patients in our operative series with adenocarcinoma of the ampulla approached the number with adenocarcinoma of the pancreas, indicating that only those with small, early lesions of the head of the pancreas were considered to be appropriate candidates for pancreatoduodenectomy. Six of the 21 patients with carcinomas of the pancreas had histologically favorable tumors (three papillary adenocarcinomas, two cystadenocarcinomas and one islet cell carcinoma), although only one of these was correctly diagnosed preoperatively or intraoperatively. Eight patients had benign conditions, half of whom underwent planned resections for chronic pancreatitis. The over-all operative mortality for our series was 13.2 per cent. The operative diagnosis was incorrect in seven patients. Excluding cystadenocarcinomas and islet cell carcinomas, four patients with carcinoma of the pancreas survived five years and six patients with carcinoma of the ampulla survived five years, with corresponding survival periods of 2.5 and 5.1 years following pancreatoduodenectomy. We conclude that: 1, pancreatoduodenectomy should be used in a highly selective manner by surgeons experienced with such operations; 2, the high diagnostic error rate and the occurrence of histologically favorable tumors of the pancreas make the arbitrary exclusion of all tumors of the pancreas for resectional therapy an unsound policy, and 3, pancreatoduodenectomy remains the best therapy for resectable tumors of the periampullary region.

Effect of preoperative irradiation on resectability of colorectal carcinomas.

From 1968 to January 1, 1977, 44 patients with initially unresectable colorectal carcinoma were treated with preoperative radiotherapy and surgery. On presentation, unresectability was determined either clinically (26 patients) or by preradiotherapy laparotomy (18 patients). Preoperative irradiation consisted of 4500-5000 rad. After radiotherapy, 33 of 44 lesions were considered resectable. Seven of 33 patients underwent incomplete resection with mean survival of 17 months. Resection was complete in 26 of the 33 patients. Of the latter group (26), 18 patients are alive with no evidence of disease with minimum follow-up of 36 months. Detailed results are discussed.

Effects of amphetamine and amfonelic acid on the disposition of striatal newly synthesized dopamine.

A comparison of the in vivo biochemical actions of the psychotomimetic central stimulants, d-amphetamine (d-AMPH) and amfonelic acid (AFA), on the metabolism of rat striatal newly synthesized [3H]dopamine (DA) was made by pulse labeling with [3H]tyrosine. No evidence for the formation of the alcoholic DA metabolites [3H]3-methoxy-4-hydroxyphenylethanol (MOPET) or [3H]3,4-dihydroxyphenylethanol (DOPET) was found in control or drug-treated animals. Both [3H]3,4-dihydroxyphenylacetic acid (DOPAC) and [3H]homovanillic acid (HVA) concentrations were increased by AFA in the presence of haloperidol, while [3H]DA content was decreased. In contrast, d-AMPH, in the presence of haloperidol, decreased [3H]DOPAC and increased [3H]DA, even in monoamine oxidase-blocked rats. Thus monoamine oxidase inhibition did not appear to be a major factor in the action of amphetamine to increase [3H]DA, but cannot be excluded as a contributing factor to the lowering of [3H]DOPAC. Similar actions of d-AMPH were seen on preformed DA. Amphetamine may release newly synthesized DA in such a way that some of the released DA enters the neuronal storage system.

Actions of danazol in vivo on cytochrome P-450 and steroidogenic enzymes in rat testis and liver microsomal preparations.

The mechanism of action of danazol has not been established and the drug may act at multiple loci. Effects suggesting inhibition of pituitary gonadotropin release have been described while some in vitro studies have demonstrated competitive inhibition of steroidogenic enzymes. In addition, destruction of cytochrome P-450 by the acetylenic moiety of danazol is a possible mechanism. Following 14 days of danazol treatment (10 mg/kg/day), the specific content of rat testis microsomal cytochrome P-450 and the serum testosterone were decreased, in spite of no significant change in serum luteinizing hormone. Furthermore, simultaneous administration of human chorionic gonadotropin with danazol still resulted in a decrease in cytochrome. The activities of two testicular microsomal steroid-converting enzymes (17 alpha-hydroxylase and 17,20-lyase) were not altered when based on cytochrome P-450 content but were markedly depressed when based on microsomal protein. In liver, danazol showed a similar but less marked dimunition of the cytochrome. Surprisingly, steroid 17 alpha-hydroxylase activity in liver was significantly increased while other cytochrome P-450 dependent enzyme activities were not altered.

Preoperative irradiation in carcinoma of the pancreas.

Seventeen patients with carcinoma confined to the pancreas and the peripancreatic area received preoperative radiation therapy in an attempt to increase the resectability rate and to reduce the incidence of recurrence. The tumors were considered either unresectable or of borderline resectability. The radiation dose ranged between 4000--5000 rads, the majority of patients (75%) receiving 4400--4600 rads in 4 1/2--5 weeks. After a period averaging six weeks the patients were reevaluated for surgery. Eleven patients were explored and six underwent radical resection. Two patients remained disease free after five years. Pancreatic resection is feasible following a course of preoperative radiotherapy to a moderately high dose. It is suggested that the response of the primary tumor to radiotherapy be used as a criterion for selecting patients for reexploration and resection.

Pre- and transoperative localization of nonpalpable breast lesions.

Percutaneous needle localization should be performed before biopsy of a nonpalpable breast lesion, thereby eliminating the need for blind biopsy. With small cancers, transoperative localization is just as important to confirm excision of the lesion and ensure that representative sections are obtained from the area in question for histologic study.

Dopaminergic neuronal responses to a non-amphetamine CNS stimulant.

The present study compares the effects of d-amphetamine (d-AMP) and the potent non-amphetamine CNS stimulant, amfonelic acid (AFA), on the firing rate of single midbrain dopaminergic (DA) neurons and on neostriatal DA metabolism (dihydroxyphenylacetic acid--DOPAC). The results indicate that AFA, like d-AMP, reduces the firing rate of DA neurons, although unlike d-AMP, AFA does not cause a decrease in neostriatal DOPAC content and, in fact, enhances that produced by haloperidol (HALO). The AFA-induced decrease in firing rate, like d-AMP, is reversed by the DA receptor blocker HALO, but again unlike d-AMP, the decrease in firing rate is not prevented by catecholamine synthesis inhibition with alpha-methyl-para-tyrosine. Thus, both amphetamine and amfonelic acid have identical electrophysiological effects on DA neurons but act by different mechanisms.

Natural history of familial medullary thyroid carcinoma: effect of a program for early diagnosis.

To detect familial medullary thyroid carcinoma in a premetastatic stage, we administered tests provocative of calcitonin secretion (infusion of calcium or pentagastrin or both) each year for seven years to members of a pedigree now numbering 107. Since 1970, 21 patients converted from normal to abnormal secretory responses (two separate tests in which calcitonin levels exceeded 0.58 ng per milliliter). Twenty of 21 glands removed showed C-cell hyperplasia, and eight of the 20 also showed foci of carcinoma. As compared to the 12 patients with tumors detected during the first year of screening, all of whom had bilateral carcinoma (seven of 12 with local metastases), later carcinomas were smaller (mean diameter of 0.2 vs. 0.8 cm), were unilateral (in all but two cases) and occurred in younger patients (mean age of 14.9 vs. 36.4 years), and none had detectable metastases.

Preoperative irradiation of primarily unresectable colorectal carcinoma.

A series of 44 patients with colorectal carcinomas considered unresectable on presentation received preoperative irradiation to a dose of 4500--5000 rad (175--200 rad/day). After a waiting period averaging 6.5 weeks, 38 patients underwent exploration. Complete resection was possible in 27 patients. Of these, 22 patients remained disease-free with a median follow-up of 27 months. While longer follow-up periods are needed, the results indicate that the large percentage of unresectable and therefore surgically incurable colorectal carcinomas can be made resectable by preoperative irradiation, and a significant number of these may have been cured.

Enhancement of air filtration using electric fields.

Although polarized electrostatic air filters are efficient air filtrating devices, their main disadvantages are difficulty in collecting conductive particles or in operating at relative humidities above 70%. We describe here a new filter design that eliminates these problems. A nonconductive media, normally a glass fiber mat, is placed between two insulated conductive screens. As the voltage across the screens is increased, the penetration of particles decreases exponentially. Increasing the electric field from 0 to 10 kV/cm will decrease the mass penetration from 60% to less than 10% of a polydispersed 0.8 micrometer ammd(sigma g = 2.0) sodium chloride aerosol. The experimental effects of face velocity, particle charge and size, packing density, fiber size, and screen insulation mirror the theoretical effects of these variables on particle penetration.