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Prior to the early 1970's, benign liver neoplasms were among the rarest of tumors. The seemingly rapid increase, especially in young females ingesting oral contraceptives, as well as the catastrophic presentation of many of the tumors resulting from liver rupture and hemoperitoneum, stimulated studies by several investigators. In the Liver Tumor Registry at the University of Louisville, we have examined the histologic material, and finalized the data on 227 tumors, the majority in young women. With few exceptions, they had used oral contraceptives or were either pregnant or immediately post-partum and presumably in a hyperestrogenic state. There have been 82 hepatocellular adenomas (HCA), 105 cases of focal nodular hyperplasia (FNH), and 31 hepatocellular carcinomas. The hepatocellular carcinomas occurred in non-cirrhotic livers, and 14 of the 31 cases were of a distinct, but rare type, polygonal cell carcinoma with lamellar fibrosis. While it seems reasonable to believe steroids play a role in adenomas and in FNH it is less certain that they produce hepatocellular carcinomas since malignant liver tumors are not uncommon in this age group without the use of oral contraceptives. With an estimated 50 million women either currently using or who have used oral contraceptives the risk must be very slight.

Studies of intrahepatic arteries in vivo and after death give dramatically different results concerning the human hepatic circulation. Corrosion casts of human liver vasculature support the existing belief that hepatic arteries are end-arteries. However, in vivo studies using angiographic techniques after ligation of either the left or the right ramus of the hepatic artery demonstrate intrahepatic translobar collateral arteries capable of perfusing the entire occluded arterial system. There is no intermediate filling of sinusoids nor of portal venules. Traditional statements that hepatic arteries are end-arteries cannot be supported by the present findings.

Replacement of glucose and albumin in ten patients after hepatic lobectomy shows that hypoglycemia and hypoalbuminemia, the two most common consequences of lobectomy in animals, can be prevented in man. Biosynthesis of protein, cholesterol, and prothrombin are reduced temporarily. In patients having emergency lobectomy, the serum bilirubin and glutamic oxaloacetic transaminase concentrations are statistically greater than in patients having elective lobectomy. Serum ammonia is not elevated and bromsulphalein excretion is normal after bilirubin returns to less than 1 mg/100 ml. Lactic dehydrogenase concentrations in serum are increased and fluctuate in the presence of sepsis or respiratory insufficiency: Mean creatine phosphokinase peaks at concentrations higher than those reported in acute myocardial infarction and returns to normal in three days. Compensatory hyperplasia of the residual lobe occurred in all patients.

Suturing of deep ruptures of the liver frequently produces complications of hemobilia, secondary hemorrhage and intrahepatic cavitation with sepsis and liver failure. Such complications require second and third risky operations in already critically ill patients. Such wounds should not be sutured, adequate drainage should be provided, low pressure venous bleeding should be controlled with temporary gauze tampons and arterial bleeding should be stopped by hepatic artery ligation. Such treatment obviates dangerous hepatic resections and morbid thoracoabdominal incisions and prevents hematobilia, secondary hemorrhage, intrahepatic cavitation and sepsis with hepatic failure.

In phase partition fixation tissue is immersed in an organic solvent at equilibrium with an aqueous phase containing a fixing agent. By using radioisotope labeling techniques the effects of phase partition fixation on protein retention during fixation of tissue with formalin and glutaraldehyde have been determined and compared with those of standard aqueous fixation using these fixatives. It has been shown that retention of protein in tissue during phase partition fixation was as good or better than during aqueous fixation. Improved retention provides further evidence that phase partition fixation may be a useful alternative to aqueous fixation.

The possible association between oral contraceptives and benign liver tumors has recently been reported. To date the majority of cases have been diagnosed as benign hepatomas (liver cell adenomas). We have had the opportunity to study 13 such cases. Eight have been examples of focal nodular hyperplasia of the liver; however, in addition, there were examples of hepatocellular carcinoma, liver cell adenoma, and possible liver cell hamartoma; all were in women on "the pill." Gynecologists are alerted to the fact that many of the patients present with symptoms of acute abdomen, syncope or shock, and intrahepatic or intraperitoneal bleeding. Prompt diagnosis and treatment may be lifesaving.

The use of hepatic artery ligation (HAL) in various clinical situations is illustrated by presenting a series of eight patients. The indications for HAL included ruptured hepatic tumors, spontaneous liver rupture, delayed hemorrhage after liver trauma, hematobilia, hepatic artery aneurysm, and hemorrhage after liver biopsy. Conventional methods of hemostasis had been used in some of these patients, but failed to control hemorrhage. The reasons for the relatively late adoption of hepatic artery ligation in treating liver hemorrhage are discussed and placed in proper prospective. Hepatic artery ligation has been shown to be such an effective method of controlling hemorrhage from the liver that other methods, such as packing and mass suture, which are unsafe and ineffective, should be abandoned. Major resection should be done only when an entire lobe of the liver is reduced to pulp or when exposure and repair of the retrohepatic vena cava are necessary.

Primary hepatic tumors developed in 13 young women who had been ingesting contraceptive steroids. Nine tumors were benign, and four malignant. Six tumors ruptured spontaneously and caused life-threatening hemorrhage. Benign tumors were successfully resected in eight women. One woman died during hepatic resection for malignant hepatoma; in two other cases of hepatocellular carcinoma, tumors were nonresectable. In two patients, the tumor was left in situ after neoplasm had been excluded by biopsy. The increase of such tumors in women of childbearing age warrants the suspicion that these contraceptive steroid hormones play an etiologic role.

Fourteen patients with post-traumatic obstructing intramural duodenal hematoma were reviewed. Seven patients underwent exploration for associated injuries. Evacuation of the hematoma was performed in two patients. Of 12 patients treated by fasting, nasogastric decompression and parenteral fluid therapy, late obstruction of the duodenum developed in one patient, and operation was required. Criteria are discussed regarding evacuation of intramural hematoma of the duodenum found at celiotomy for associated injuries. In the typical patient with an isolated intramural hematoma in whom no other indications for operation are identified, aggressive nonoperative therapy is the preferred treatment.

Twenty-six cases of colonic volvulus from the University of Kentucky Medical Center and the Lexington Veterans Administration Hospital, covering a ten-year period, are presented. Overall mortality was 19 per cent (5 of 26 patients). Cecal volvulus carried the greatest mortality, 30 per cent (3 of 10 patients), whereas sigmoidal volvulus had relatively low mortality rate of 7 per cent (1 or 15). A single patient who had volvulus of the transverse colon died. The most significant factor leading to death was not necrotic bowel but the necessity for emergency operation in these generally debilitated patients. A plan of management with the major aim to convert emergency situations into elective or urgent ones is presented with the expectation that the mortality rate can be improved.

This study examines experience with over 250 liver tumors in young women. Most were oral contraceptive related. There were two distinct benign liver tumor types: focal nodular hyperplasia and liver cell adenoma. Six benign liver tumors were examined for estrogen receptors. They did not contain significant quantities of estrogen receptor, supporting experimental studies of an epigenetic origin. Multiple tumors occurred in about 20% of cases but did not change the favorable prognosis associated with benign tumors. The most significant source of morbidity and mortality was spontaneous hemorrhage or rupture. Twenty-three women in this series had hepatocellular carcinoma and the majority of these were associated with prolonged steroid usage. These malignant liver tumors occurred in young females without cirrhosis or other factors known to be associated with hepatic malignancy. Unlike "hepatocellular carcinomas" reported in males taking anabolic androgenic steroids, the tumors in females had a high rate of metastasis to a variety of organs. The risk of liver tumors in oral contraceptive users remains unknown, but must be very small since an estimated 150 million women worldwide and 40 million in the U.S.A. have used oral contraceptives.

Many wounds of the liver are minor and require no corrective operations. If these patients are not killed by associated injuries, they usually survive. Hemorrhage from hepatic wounds is the most common cause of death. Selective ligation of appropriate blood vessels swiftly controls bleeding and does not cause septic hepatic necrosis because the liver in humans is sterile and collateral blood flow prevents complete infarction of hepatic tissue. Hepatic resection is dangerous in acutely hypovolemic patients, but hepatic resection is beneficial in treating the late complications of hepatic trauma. Liver-related sepsis after trauma to the liver can be obviated by elimination of gauze packs, absorbable hemostats, peritoneal drains, sutures and choledochal tubes.

Selective ligation of sundry hepatic arteries in patients with hepatic trauma obviated death from hepatic bleeding in 59 of 60 patients treated with this method of hemostasis. Hepatic insufficiency did not occur in survivors. Reconstitution of intrahepatic arterial flow is rapidly accomplished by collateral arteries. When the source of hemorrhage is perihepatic, that is, hepatic veins and retrohepatic vena cava, hepatic artery ligation is ineffective. Two patients died from this kind of hemorrhage.

Experience with pathological material from 150 women with liver tumors is reviewed. The features of liver cell adenoma and focal nodular hyperplasia are sufficiently different that the vast majority of the benign tumors can be easily subclassified. Although most occurred in women ingesting steroids, the wide usage of oral contraceptives makes it difficult to prove a causative role. Nineteen of the tumors were malignant and, to date, 12 of those patients have died of their disease. Since hepatomas are much more common than benign liver tumors, one must be even more circumspect in indicting steroids in their causation. In this group of women none had cirrhosis, whereas in the general population cirrhosis is a very common precedent lesion. Further investigation of estrogens and primary liver carcinoma would be timely.

A registry of liver tumors was started in late 1973 in an attempt to assess the relationship of these tumors to oral contraceptives or to other environmental factors. This report is concerned with the pathological aspects and the possible pathogenesis of the first 101 tumors accessioned. There were 44 instances of focal nodular hyperplasia, 40 adenomas, four unclassified but probably benign tumors, and 13 hepatocellular carcinomas. Eighty-one patients took oral contraceptives; six were associated with pregnancy; three had taken estrogens for long periods of time; one had a thecoma; four never took sex steroids; and in five the history was unknown. Tumor rupture and intrahepatic hemorrhage were frequent complications. It is possible that the vascular lesions associated with focal nodular hyperplasia could play a part in their pathogenesis as well as with rupture. Foci of adenomatous hyperplasia may be related to the development of adenomas. The association of these tumors with sex steroids could be coincidental. The fact that none of the patients had cirrhosis of liver fibrosis, and that androgenic anabolic steroid therapy has been associated with hepatocellular carcinomas in males, suggests that further study of the problem is necessary.

Hospital and anesthesia records of 39 patients who had hepatic artery ligation for severe hepatic trauma were analyzed retrospectively to acquire information on any relationships between choice of anesthetic, preoperative physical condition of the patient, type and incidence of complications, and mortality. Patients who had lost the most blood received neuroleptanalgesia, ketamine, or cyclopropane; those with more stable cardiovascular status received halothane; those in severe circulatory compromise received only oxygen and muscle relaxants. Trends in results of postoperative liver function tests were not related to type of anesthesia. Of the 12 deaths, seven were due to massive bleeding, three to septicemia, one to multiple complications, and one to hepatorenal failure 18 days postoperatively. Choice of anesthetic agent appeared to have no significant influence on postoperative morbidity and mortality; rather, the choice of anesthesia depended on the preoperative physical (especially hemodynamic) status of the patient, which in turn reflected the apparent blood loss estimated at induction.