Hugh A. Edmondson

Fibrolamellar carcinoma of the liver: A tumor of adolescents and young adults with distinctive clinico‐pathologic features

Clinical and pathologic features of 23 patients with a distinctive histologic and clinical variant of hepatocellular carcinoma are summarized. The variant pattern of hepatocellular carcinoma is most common in the age group 5–35 years and occurs equally in either sex. The distinctive histologic features include 1) deeply eosinophilic neoplastic hepatocytes, many of which contain intracytoplasmic hyaline globules and distinct pale bodies and 2) fibrosis arranged in a lamellar fashion around the neoplastic hepatocytes.

Liver-cell adenomas associated with use of oral contraceptives.

During the past six years an increasing number of liver-cell adenomas in women were diagnosed, and we undertook a study of possible etiologic factors, including use of oral contraceptives, in 42 women. There was a significant difference between cases and matched controls in mean months of oral-contraceptive use: 73.4 as compared to 36.2 (P less than 0.001). The women with adenomas took mestranol-containing pills much more commonly than the controls (P less than 0.0001). Hemorrhage into the tumor was often associated with the onset of menstruation in women taking oral contraceptives. Long-term use of oral contraceptives, especially those containing a high total dose of steroids or mestranol as the synthetic estrogen, should be balanced against risks of side effects of the drugs.

Cystadenoma with mesenchymal stroma (CMS) in the liver and bile ducts. A clinicopathologic study of 17 cases, 4 with malignant change

This study of 17 cases describes a homogeneous clinicopathologic group of tumors previously subsumed under the general term, hepatobiliary cystadenoma. This unique group of neoplasms that the authors have termed “cystadenoma with mesenchymal stroma” (CMS), occurred exclusively in women and showed two essential tumor components: (1) a cyst lining of columnar to cuboidal, mucin secreting epithelium; and (2) a moderately to densely cellular stroma composed of spindle (rarely oval) cells. The stromal element appeared similar to primitive mesenchyme, both on light and electron microscopic study, showing variable differentiation toward fibroblasts, smooth muscle, adipose tissue and capillaries. Cases of hepatobiliary “cystadenoma” in the literature with histology similar to CMS had similar sex and age incidences, while histologically dissimilar cases, lacking the mesenchymal stroma, had significantly different parameters. Four cases of CMS in this series showed malignant change that was manifested as papillary adenocarcinoma, suggesting the need for complete surgical removal of these premalignant neoplasms.

Regression of Liver Cell Adenomas Associated with Oral Contraceptives

The regression of liver cell adenomas that follow the use of oral contraceptives when steroids are withdrawn was observed in three patients. At diagnosis by needle biopsy in patients without pain or evidence of hemorrhage, prompt cessation of steriod use is suggested as the preferable form of treatment. The same is true for the diagnosis made at surgery if the tumor or tumors are difficult to remove.

Trypsin, trypsinogen and trypsin inhibitor in human pancreatic juice.

Abstract 1.1. Benzoylarginine-paranitroanilide was employed as substrate in a method which permits simple, sensitive and rapid assay of trypsin. 2.2. Human pancreatic juice obtained by catheter drainage of the duct of Wirsung exhibited no spontaneous tryptic activity. It does, however, contain substantial amounts of spontaneous trypsin inhibitor. Human pancreatic juice inhibitor, which is soluble in trichloracetic acid, is not digested by trypsin. 3.3. Trypsinogen in human juice is not activated by incubation with bile, streptokinase-streptodornase, calcium ion, magnesium ion, barium ion, ammonium ion, or acidification of juice to a pH of 4.5. Bovine or human trypsin does not activate or only slightly activates trypsinogen in human pancreatic juice. However, the addition of small amounts of calcium markedly enhances the conversion of trypsinogen to trypsin by trypsin. Slight tryptic activity was noted in human juice, which had been frozen for several months, when incubated in calcium ion. 4.4. Trypsinogen in juice undergoes autodegradation even though no measurable trypsin is present. Calcium ion retards this reaction. In many instances addition of trypsin to pancreatic juice enhanced degradation of trypsinogen. 5.5. Enterokinase actively converts trypsinogen in juice to trypsin. The time of maximal conversion is inversely proportional to the amount of enterokinase. 6.6. Calcium ion enhances conversion of trypsinogen to trypsin in pancreatic juice in many ways. These may explain the association of pancreatitis with hyperparathyroidism.

Protein binding of pancreatic proteolytic enzymes.

In human serum there are two protein fractions that are potent inhibitors to trypsin. These inhibitors travel with the a1-globulin and a2-globu-lin fractions when serum proteins are separated by electrophoresis (1-3). One ml of normal serum has sufficient amounts of trypsin inhibitor to neutralize the proteolytic effect of 1.15 (± 0.10) mg of crystalline trypsin. Approximately 90 per cent of the trypsin inhibitory proteins in serum migrate in the electrophoretic cell with the a1-globulin fraction, and the remainder with the a_2-globulin fraction (3). It is known that in many diseases of unrelated etiology the level of total serum trypsin inhibitor may be increased. This increase, therefore, is not specific for any disease, including acute pancreati-tis. Also, it is likely that an increase in the a1-globulin trypsin inhibitor is no more specific in the various diseases than is a sedimentation rate. However, the results of a previous study indicate that in acute pancreatitis the a2-globulin inhibitor decreases, and in severe pancreatitis it frequently disappears. The divergent changes of the two serum globulin trypsin inhibitors in acute pancre-atitis result in a marked increase in the ratio of the a,-to a2-globulin trypsin inhibitors. The decrease in the a2-globulin trypsin inhibitor in acute pancreatitis has been helpful in our laboratory in the diagnosis of acute pancreatitis (3). The determination of the serum a1,-and a2-glob-ulin trypsin inhibitors involves the lengthy procedure of serum protein separation by electrophore-sis, elution of protein fractions which involves many hours, and then the determination of the trypsin-inhibiting capacity of the protein fractions. The present complexities of this procedure make the determination difficult for the routine hospital laboratory. Because of these factors we sought methods that would permit an easier assay of the a2-globulin trypsin inhibitor. Many studies were made which included the determination of the inhibiting activities of the a,-and a2-globulin fractions to chymotrypsin, elastase, thrombin, plasmin, and collagenase. Although interesting data were obtained, these studies did not permit the differential assay of the serum a1-and a2-globu-lin trypsin inhibitors unless electrophoresis was done. Continuing along this line of investigation, we determined that when trypsin was added to serum and the mixture subjected to electrophoresis, a substance with trypsin-like activity was detected, migrating with the a2-globulin fraction. This was an unexpected finding, since the serum to which trypsin was added contained sufficient trypsin in-hibitor to completely neutralize many times the amount of trypsin added. Also, other known in-hibitors of trypsin and …

Sclerosing Hyaline Necrosis of the Liver in the Chronic Alcoholic: A Recognizable Clinical Syndrome

Excerpt In recent years we have observed a group of alcoholic patients who present a symptom complex accompanied by a distinctive morphologic lesion in the hepatic cells that has been known as alco...

Hypertension and cardiac rupture

Abstract 1. 1. In a series of 25,000 autopsies at the Los Angeles County Hospital between July 1924, and August 1941, there were 865 hearts which contained unhealed infarcts caused by coronary disease. 2. 2. Among these were 72 instances of spontaneous rupture through an area of ventricular infarction; 50 (70 per cent) were on the anterior surface of the heart. In 13 instances the rupture was through the interventricular septum. 3. 3. Scarring was present in 58.4 per cent of the unruptured hearts and in only 26.3 per cent of the ruptured hearts. 4. 4. In the ruptured hearts the infarcts tended to be smaller, more completely necrotic, and more heavily infiltrated with polymorphonuclear leucocytes. 5. 5. Of 100 patients who had nonfatal myocardial infarction, 23 (23 per cent) had a blood pressure of 140 90 or above. The average blood pressure was 125 78 . 6. 6. Of 657 patients who had myocardial infarction that terminated fatally without rupture, 210 (32 per cent) had a blood pressure of 140 90 or above. The average was 128 81 . 7. 7. In 62 patients who died as a result of cardiac rupture, the blood pressure was 140 90 or above in 39 (63 per cent). The average was 148 93 . 8. 8. The average calculated time between infarction and rupture was 7.4 days. Ninety-eight per cent occurred on or before the sixteenth day after infarction. Seventy-eight per cent occurred between the third and twelfth days. 9. 9. Among 368 patients with heart weights of 400 grams or more and a blood pressure of less than 140 90 after infarction, only 4 per cent had cardiac rupture. 10. 10. Rupture of the heart occurred in 25 per cent of the 28 patients whose hearts weighed less than 400 grams and whose blood pressures were 140 90 or above after myocardial infarction. 11. 11. In the first 12,500 autopsies in this series, done between 1924 and 1935, 266 instances of myocardial infarction and 23 (8.6 per cent) ruptures were observed. In the second half, done between 1935 and 1941, myocardial infarcts were present in 599 cases and ruptures in 49 (8.2 per cent).

Ciliated hepatic foregut cyst.

This study describes a solitary unilocular cyst of the liver, lined by ciliated, pseudostratified, columnar epithelium supported by a loose, relatively acellular lamina propria. The cyst wall was composed of a prominent smooth muscle band, of up to three layers, surrounded by an outer fibrous capsule. These features distinguish the cyst from biliary cystadenoma and make it histologically similar to previously described ciliated bronchial and esophageal cysts. This ciliated hepatic cyst and similar bronchial and esophageal cysts appear to represent a common spectrum of derivatives from the embryonic foregut. Cysts of this type have not been generally recognized to occur in the liver.

Colonic fistulization due to pancreatitis

S PONTANEOUS COLONIC FISTULIZATION due to p a n c r e a t i t i s is u n c o m m o n ; on ly four teen recorded cases were found in a rev iew of the l i t e ra ture . T h e purpose of th is r e p o r t is to record the c l in ical and pa tho log ic fea tu res of four a d d i t i o n a l cases encoun te red a t the Los Angeles C o u n t y H o s p i t a l dur ing the l as t t w e n t y years . Two s ignif icant f ea tu res were demons t r a t e d b y these cases. F i s t u l i z a t i on never occur red dur ing the in i t ia l acu te phase of pancrea t i t i s , r a t h e r i t t ook p lace l a t e r dur ing the evo lu t ion of pe r ipanc rea t i c s u p p u r a t i o n or pseudocys t . Also, f i s tu l iza t ion fai led to influence f a v o r a b l y the course of t he p r i m a r y disease. I t n o t on ly fai led to decompress the pe r ipanc rea t i c col lect ion successful ly as m i g h t be expec ted b u t also a p p e a r e d to induce m a j o r hemor rhage and dea th .