Ichio Honjo

Cumulative Results in 57 Institutions in Japan

In this study the experiences with carcinomas of the pancreas, ampulla of Vater, terminal comma bile duct, and duodenum found in a series of 3,610 patients collected from 57 major Japanese institutions was compiled over a 26 year period. The results were analyzed as to the success of resectional and palliative surgery for the various lesions. The most common lesion was carcinoma of the head of the pancreas. Unifortunately, only 18.3% of these patients were resectable with a 25.3% mortality. Carcinoma of the body and the tail was the second most frequent lesion, and it also exhibited a low resection rate. Carcinomas of the ampulla and the terminal common bile duct and duodenal regions were the most favorable for resection; usually pancreatoduodenectomy with an overall mortality of 20.8%. As a result of the large number of pancreatectomies performed, there was also a large number of postoperative complications, the most frequent being leakage at an anastomotic line. Hemorrhage also occurred frequently. Distal pancreatectomies were reserved for carcinoma of the body and the tail of the pancreas, and the most common postoperative complication of this procedure was hemorrhage. There were only 45 total pancreatectomies among the 973 resections being performed most frequently in patients with carcinoma of the head of the pancreas. Again, the most frequent postoperative complication was hemorrhage, followed by anastomotic leakage. The long term survivals following resection for these lesions were each poor. The best mean survival time was 22.7 months for carcinoma of the ampulla of Vater. Patients having resections for carcinoma of the head of the pancreas had a mean survival time of 12.3 months. At 5 years there were few survivors and most of them were patients who had undergone resections for carcinoma of the ampulla of Vater.

Surgical significance of anatomic variations of the hepatic artery

Abstract By means of selective arteriography, anatomic variations of the hepatic artery in 200 patients were observed. They were classified into three groups on the basis of the number of the hepatic arteries. The classification has a more direct significance to surgery of the upper abdominal organs than those proposed by anatomists. The single hepatic artery classification was applicable in 58.5 per cent of the cases, in which the normal “textbook” pattern was limited to 53.5 per cent (107 of 200 cases). The double hepatic artery group consisted of 37.0 per cent of the cases and the multiple hepatic artery group 4.5 per cent. Each group was further divided into the celiac, mixed, and mesenteric types according to the origin of the hepatic artery. Combination of the three groups and three types yielded twentyseven different distribution patterns of the hepatic artery. In addition, surgical significance of the classification was illustrated in cases of tumors of the liver and pancreas.

Ligation of a branch of the portal vein for carcinoma of the liver

Portal branch ligation, a new surgical treatment for unresectable carcinoma of the liver, was performed in twenty patients. All the patients tolerated the procedure, and morbidity and mortality were minimal, even in patients in poor general condition. The responses to ligation differed considerably, but significant palliation was attained in some patients and one survived six years. The effect of portal branch ligation on the tumor appears to be closely related to the degree of tumor vascularity, tumor malignancy, and portal circulatory disturbances such as cirrhosis, portal hypertension, or portal thrombosis. We believe that the present procedure can be recommended for clinical application in some patients with unresectable carcinoma of the liver.

Human liver mitochondria

Abstract Contamination with hemoglobin in human liver mitochondria prepared by the procedure commonly applied to rat liver is unavoidable and a major obstacle to the measurement of cytochromes by (reduced minus oxidized) difference spectra. The washing of sliced liver tissues with Locks solution minimized the contamination with hemoglobin. A systematic method has been presented for quantitatively estimating the respiratory pigments without complete removal of hemoglobin. Phosphorylative activity and respiratory enzyme contents were assayed in the mitochondria prepared from 67 biopsy specimens of normal human liver obtained at operation. The maximal phosphorylation rates were 41.7 nmoles ATP synthesis per mg protein per min at 22° with glutamate plus succinate as substrates (on a protein basis) and 36.6 per second (on a cytochrome a (+ a 3 ) basis, “cytochrome a (+ a 3 )-turnover”). No statistically significant decline in the phosphorylation rates with increasing age could be demonstrated. The cytochrome a (+ a 3 ) concentration was fairly constant during the life span, while there was a significant elevation of cytochrome c + c 1 concentration with increasing age. After 70 years of age the cytochrome c + c 1 level increased 1.6-fold, from 76 to 121 pmoles per mg of mitochondrial protein, as compared with young adults. In the young adult cytochrome c + c 1 concentration did not exceed that of cytochrome a (+ a 3 ). The ratio of cytochrome c + c 1 to cytochrome a (+ a 3 ) increased after 60 years of age, and cytochrome c + c 1 concentration was 1.5 times higher than the cytochrome a (+ a 3 ) concentration after 70 years of age.

Clinical classification of hepatoma in Japan according to serial changes in serum alpha-fetoprotein levels

Quantitative determinations of serum alpha‐fetoprotein (AFP) in 96 patients with hepatomas have demonstrated three main groups based on changes in the serial levels: 1) patients with more than 10 000 ng/ml during most of their clinical course, and with an increase of 10 000 ng/ml or more in a week (Group A); 2) patients with levels varying from 200 to 10 000 ng/ml and with an increase of 1000 ng/ ml in three to four months (Group B); and 3) patients with serum AFP levels below 200 ng/ml during most of their clinical course (Group C). The patients in Group A had a mean survival time of 7.62 ± 3.97 months, and those in Group B, 16.18 ± 12.18 months. The patients in Group C were subdivided into two groups according to whether survival time was long (33.92 ± 28.22 months) or short (3.75 ± 0.87 months). Histologic findings revealed poorly differentiated carcinoma in patients in Group A, moderately differentiated carcinoma in those in Group B, and well differentiated carcinoma in those with long survival in Group C and anaplastic carcinoma in those with short survival in Group C.

Significance of glucose tolerance as prognostic sign in hepatectomized patients

Glucose tolerance was determined in fourteen patients with cancer of the liver. The patients with parabolic GTT patterns fared relatively better than did those with linear GTT patterns. In the patients with successful extended right hepatectomy, gradually increasing and long-standing hyperglycemia (linear GTT pattern) in response to an oral glucose load was not observed after hepatectomy and the insulin response was significantly greater than that in controls. However, in the patient with unsuccessful extended right hepatectomy, the linear GTT pattern continued for a more prolonged period after hepatectomy.

Insulin requirements for hepatic regeneration following hepatectomy.

On the basis of changes in the adenine nucleotide the mitochondrial metabolism of the remnant liver, insulin requirements for hepatic regeneration were studied in diabetic rats treated with varying amounts of alloxan. Mildly diabetic rats with less than 30% inhibition in maximal portal insulin response to oral glucose load, showed a parabolic glucose tolerance pattern and could tolerate partial hepatectomy. Whereas, severely diabetic rats with more than 45% inhibition showed a linear glucose tolerance pattern and died within 24 hours after partial hepatectomy. In the former rats, the energy charge (ATP + 1/2ADP/ATP + ADP + AMP) levels of the remnant liver decrease slightly at an early period after partial hepatectomy but could be restored rapidly to normal levels with a concomitant rise of oxidative phosphorylation in remnant liver mitochondria. In contrast, the energy charge levels in the latter groups fell more markedly and could not be restored, because of insufficient enhancement of mitochondrial oxidative phosphorylation. It is suggested that an enhancement in mitochondrial phosphorylative activity of the remnant liver following partial hepatectomy is inhibited in proportion to the severity of impaired insulin secretion, resulting in a decrease of the potential functional capacity of liver.

Clinical Application of Cytochrome a(+a3) Assay of Mitochondria from Liver Specimens: An Aid in Determining Metabolic Tolerance of Liver Remnant for Hepatic Resection

Measurement of cytochrome a(+a(3)) contents in liver mitochondria was made on 52 biopsy specimens of patients with liver tumor. Patients having higher cytochrome a(+a(3)) contents in mitochondria from remaining liver than those of normal human liver mitochondria could survive well major liver resections whether or not associated with liver cirrhosis. However, patients with cytochrome a(+a(3)) contents less than 0.5 x 10(-10) moles per mg protein showed a high rate of postoperative complication (80%) and death (40%) in spite of minor operation. In routinely used liver function tests such as serum albumin, A/G ratio, SGOT, total bilirubin, prothrombin time, BSP and TTT, there were no significant differences between patients with cytochrome a(+a(3)) contents more than 0.5 x 10(-10) moles per mg protein and those less than 0.5. The results indicate that routine laboratory studies do not have much diagnostic value in estimation of a marked decrease of mitochondrial cytochrome a(+a(3)) contents. It is suggested that the measurements of cytochrome a(+a(3)) of the remnant liver should be done prior to a contemplated major resection.

Changes in carbohydrate metabolism and endocrine function of remnant pancreas after major pancreatic resection

Changes of glucose tolerance after partial pancreatectomy were divided into three types depending on the extent of resection. When 88 per cent or more of the pancreas was resected, hyperglycemia developed immediately, and when 70 to 88 per cent of the pancreas was resected, diabetes occurred after six weeks or more, but diabetes did not develop at all when less than 70 per cent of the pancreas was removed. The secretion of glucagon was maintained well, but that of insulin was easily impaired after resection of 70 per cent or more of the entire pancreas.

Role of insulin as a portal factor in maintaining the viability of liver.

The subcutaneous administration of insulin did not induce a significant effect on oxidative phosphorylation of the mitochondria from normal rat liver. However, in rats subjected to ligation of a branch of portal vein, the phosphorylative activity of the mitochondria from the ligated lobe deprived of portal blood fell rapidly and at 12 hours decreased to approximately 50% of nomal liver mitochondria. After the insulin administration, the phosphorylative activity of the mitochondria from ligated lobe was rapidly stimulated within 30 minutes, reached the maximal level of normal liver mitochondria at 2 hours (p < 0.005) and then fell to subnormal levels. The respiratory control ratio, state 3 respiration and P/O ratio remarkably increased in parallel with an increase of phosphorylative activity. The contents of respiratory enzymes making up ATP remained unchanged. Considering the previous report that a factor, which is capable of stimulating oxidative phosphorylation of the liver mitochondria, is present in portal blood, it is suggested that insulin may play an important role in the mechanism by which the portal blood controls mitochondrial metabolism.