Do synchronous colonic cancers arise from intracolonic metastatic spread?

SELECTED SLJMMARIES 2039

June 1987

ing in patients studied. Comment.

with

delayed

gastric

emptying

when

The results of this study are both surprising and disturbing. The gastric emptying abnormality in anorexia nervosa and its response to either metoclopramide or domperidone have been described before (Gastroenterology 1979;77:319-23; Dig Dis Sci 1985;30:713-22). Although the abnormality does not appear to be caused by the decreased body weight, in that patients with malnutrition and weight loss associated with inflammatory bowel disease do not have a delayed gastric emptying [Dig Dis Sci 1985;30:713-22), it is not known whether the gastric emptying disorder causes the eating disorder or vice versa. Despite evidente that prokinetic agents such as domperidone improve the gastric emptying in patients with anorexia nervosa ip whom a delayed gastric emptying is demonstrated, there are no reports of the efficacy of treating the gastric emptying disorder on the psychiatrit aspects or long-term weight of patients with this disorder. The esophageal motility findings in this study are quite disturbing. The criteria for making the diagnosis of primary anorexia nervosa are (a) age of onset before 25 yr; (b) anorexia nervosa with an accompanying weight loss of at least 25% of original body weight; (c) a distorted implacable attitude toward eating, food, or weight; (d) no known medical illness that could account for the anorexia nervosa and weight 10s~; and (e) no known psychiatrie disorder such as primary affective disorders, schizophrenia, and obsessive-compulsive and phobic neuroses. Criterion (9) is the difficult one. How far does one have to evaluate a problem before deciding that there is no underlying physical illness? Unfortunately the authors have not outlined how the “experienced psychiatrists” and ether “competent physicians” evaluated their patients before deciding on the diagnosis of anorexia nervosa. Achalasia is an underdiagnosed disorder in which symptoms may be present for years before the diagnosis (Br Med J 1964; 1:1135~0). In the early stages, there may not be the classica1 findings ofa dilated esophagus and bird beaked distal esophagus. It is also conceivable that a young woman might find the lack of desire to eat because of dysphagia and the subsequent loss of weight desirable; however, one would expect a history of dysphagia when asked for. Although a detailed history can differentiate between dysphagia and anorexia, this differente can be easily missed if specific questions are not asked, particularly of a less articulate patient. It is not clear how detailed a history or even evaluation was conducted in these patients. The pattern of referral is unknown and it was hopefully not via gastroenterologists. In my institution the pattern of referral to psychiatrists of patients thought to have anorexia nervosa is mainly via family practitioners, self-referral, or family members. A gastrointestinal evaluation with barium studies or manometry is not routinely performed, indicating that the history is the main step in deciding any further diagnostic steps. Psychological profiles in patients with functional bowel syndromes, such as esophageal motility disorders, have suggested that such patients have a greater frequency of psychiatrie diagnoses than controls (N Eng1 J Med 1983;309:1337-42). In this study no patients had anorexia nervosa. NO psychological profiles have been reported in patients with achalasia. In the article under discussion, the authors suggest that al1 patients with suspected primary anorexia nervosa should have disordered esophageal motility excluded as a cause for their illness. In the same journal is an editorial by a psychiatrist (Gut 1986;27:1115-9), who disagrees. He feels that there may have been an error in making the disagnosis of anorexia nervosa and emphasizes that the diagnosis of anorexia nervosa can be made on positive grounds rather than by the exclusion of ether diseases. The significante of this article depends on the evaluation of these patients. If a detailed history for gastrointestinal disorders and ether medical disorders that can

result

in anorexia

and weight

loss

was obtained,

and if the

psychologie history and behavior of the patients truly suggested that they demonstrated a pathologie attitude to weight gain, the conclusions would be valid and the findings would have relevance to al1 patients suspected of anorexia nervosa. This article, however, fails to report on this most important evaluation and therefore it would be premature to follow the advice of the authors in instituting an expensive and somewhat uncomfortable evaluation for al1 patients. One should accept the message that it can be possible for even experienced psychiatrists and internists to make a premature diagnosis of anorexia nervosa and one must be vigilant not to make assumptions based on a young female patient with pathologie weight 10s~. A. OUYANG, M.D.

DO SYNCHRO~OUS COLONIC CANCERS ARISE FROM INTRACOLONIC METASTATIC SPREAD? Schwartz D, Banner ments of Pathology and Rush-Presbyterian, cago, Illinois) Origin mas. A retrospective 58:2082-8.

BF, Roseman DL, Coon JS (Departand Surgery, Rush Medical College St. Luke’s Medical Center, Chiof multiple “primary” colon carcinoflow cytometric study. Cancer 1986;

Synchronous colonic cancer, or the simultaneous presentation of multiple primary large bowel tumors occurs in -2%-6% of al1 colon cancer patients and has been documented in the literature for over 100 yr. The question asked in this study was whether such tumors arise as independent primaries or from transluminal or intramural spread. The technique of flow cytometry has been used to measure nuclear deoxyribonucleic acid content in normal, premalignant, and malignant epithelium. Tumor cells may contain normal (diploid) or abnormal (aneuploid) amounts of DNA. In this retrospective study, 23 previously fixed, paraffinized colon carcinomas from 10 patients were analyzed for DNA ploidy using flow cytometry. The results indicated the following three main subgroups: (a) tumors with differing DNA ploidy, (b) tumors were al1 diploid, and (c) tumors with identical DNA aneuploidy. Fiftyseven percent of al1 tumors revealed only a single diploid peak, the remainder having clearly defined aneuploid and diploid populations. An imperfect correlation was noted between the percentage of cycling cells, assessed parametrically, and the histologically observed mitotic rate. One possible source of error in estimating (S + Gz M) phases may have come f!om the presence of inflammatory and stromal cells present in the tumors. There was no correlation between tumor histology and any of the three subgroups. NO correlation was present between histoiogy and DNA ploidy. The authors conclude that the group 3 results showing multiple tumors with identical aneuploidy within each tumor is strongly suggestive of intracolonic metastatic spread from a single primary site. Comment. The recent development of techniques (J Histochem Cytochem 1983;31:1333-5) to analyze fixed, paraffin-embedded pathologie material for cellular DNA content has sent numerous investigators off into the pathology archives to perform valuable retrospective studies. Because synchronous tumors are relatively

2040

SELECTFD SUMMARIES

GASTROENTEROLOGY Vol. 92, No. 6

rare, it could take a considerable

time to obtain a statistically valid sample size. The material used in this study was obtained over a 3-yr period, but stil1 the numbers were too smal1 for any statistical analyses. Based on these preliminary results it would now seem worthwhile to increase the sample sizes in order to confirm the significante of the initial conclusions. In such studies it is important to adhere to strict pathologie criteria for the diagnosis of multiple primary tumors (Am J Cancer 1932;16:1356-414). A considerable number of flow cytometry DNA studies have been recently published. The reported incidence of DNA aneuploidy in colon carcinomas has ranged from 39% to 74%. Abnormal DNA ploidy has been related to a more aggressive overall clinical course (J Nat1 Cancer Inst lQ82;69:15-22). The correlation between DNA ploidy and tumor grade has been poor. A major premise in the present stucly is that an independent origin of two or more fumors having identical DNA aneuploidy within one colon would he a highly unlikely ‘event. The authors address this potential concern by probability analyses of individual cases. A fucher observation was that tumors with identical DNA from a single colon may exhjbit markedli different histopathologie features. Thus, although the genotype may be similar, phenotype can differ significantly. The present paper also suggests the converse is true, namely the histoiogic similarity does not always imply a single origin. L. R. JACOB&

M.D.

MUSCLE POWER +4ND GLUCC)SE/POTAS$IUM IN UNIlERNOU~SIJED PATIENTS Chan STF, McLaughlin SJ, Ponting GA, et al. (Academie Surgicai Unit, St. Mary’s Hospita& London, United Kingdom) MuscIe power after glucose-potassium loading in undernourished patients. Br Med J 1986;293:1055-6. This paper studied muscle functjon by electrical stimulation and showed tbat the ratio of the low to the high frequency response was ipcreased, and the relaxation rate slowed, in rr+alnourished preoperative patients. By giving a high glucose (25 kcal/kg . day as 20% dextrose) and potassium infusion (20 mmol&OO ml glucose) they normalized muscle function. Comment. This paper confirms our earlier observations that the maxima1 force at higher frequenties is reduced [and thus the resulting ratio of low to hjgh frequency force is raised) in malnourished humans and animals. The relaxation rate is also slowed.‘This paper shows that short-term (48 h) refeeding can correct these abnormalities, presumably before any possible increase in truc lean body mass. Thus the feeding of energy and intracellular electrolyte appear to be important. Clearly these findings are of ipterest because they indicate that functional abnormalities related to malnutrition can be reversed separately from tissue growth, and that short-term feeding may be of benefit before surgery. This and other studies open a new way of looking at malnutrition apd refeeding. K. N. JEEJEEBHOY,

SYMPATHETIC

TONE IN CIRRHOSIS

Willet 1, Esler M, Jennings Service, Research

Baker Medical Unit, Alfred

M.D.

G, Dudley F (Gastroenterology

Research Hospital,

Institute, and Clinical Melbourne, Australia)

Sympathetic tone modulates portal venous pressure in alcoholic cirrhosis. Lancet 1986;ii:93942 (October 25). The clinical picture presented by many alcoholic cirrhotic patients often suggests the presence of excess activity of the sympathetic nervous system. Tachycardia and increas’ed cardiac output are the major hemodynamic findings to support such an association. pblockers such as propranolol have been shown to decrease exchangeable body water and sodium when given over a period of months to cirrhotic patients (Lancet 1984;51:1064-8), whereas acutely they can cause a decrease in splanchnic blood flow. Their effect on wedged hepatic vein pressure has been variable. An effect of the sympathetic nervous system on splanchnic hemodynamics might have important clinical implications, but assessment of sympathetic tone has remained difficult and controversial. The present study addresses the question of whether centra1 inhibition of sympathetic tone by a drug such as clonidine could affect portal pressure. Sixteen male alcoholic cirrhotics with biopsy-proven cirrhosis, endoscoplcally confìrmed esophageal varices, and a hepatic gradient (wedged hepatic vein pressure or wedged hepatic vein pressure minus free hepatic vein pressure or free hepatic vein pressure) >lO mmHg, were studied. They were as stable as such patients ever arethat is, none bad bled for at least 3 wk, they were off alcohol for the same period of time, and they had not received diuretics for at least 5 days. Plasma levels of norepinephrine reflect two separate processes-release of norepinephrine into plasma from sympathetic nerves and its subsequent removal from the circulation. Esler et al. (Life Sci 1979;25:1461-70) reported a technique for determining “total noradrenaline spillover.” This determination, which they claim is a valid assessment of sympathetic tone, involves infusing tritiated noradrenaline in order to achieve a plateau state of the labeled material in the plasma. Once a steady leve1 has been obtained, division of the steady state infusion rate by the specific activity of plasma noradrenaline is a measure of the rate of release of the hormone into the circulation and hence an estimation of sympathetic tone. This technique yields a mean leve1 of 296 ng/min in normal men. Cirrhotic patients have a mean leve1 of 755 ng/min. When clonidine, an a-2-agonist with centra1 inhibitory effects on sympathetic activity, was given intravenously, the “noradrenaline spillover rate” in the cirrhotics fel1 to mean leve1 of 378 ng/min. During these studies 6 patients underwent simultaneous cannulation of the hepatic and portal veins. The mean pressures in both vessels were the same (31.8 and 31.5 mmHg), which is the usual pattern in alcoholic cirrhosis. Clonidine produced a fa11 of 5.8 mmHg in the hepatic vein and 6.0 mmHg in the portal vein. Ten of the patients underwent studies of systemic and splanchnic hemodynamics. In these studies arterial blood pressure fel1 by 23% after clonidine. Cardiac output was high in the cirrhotic patients but fe!l from 7.03 L/min to 6.08 Wmin when clonidine was given. The hepatic blood flow, which was determined by the Indocyanine green extraction method, remained unchanged after clonidine whereas there was a fa11 in the hepatic gradient from 18.6