Serum ferritin level is higher in poorly controlled patients with type 2 diabetes and people without diabetes, aged over 55 years.

AIMS: Diabetes mellitus has been increasing in Mongolia. There is also growing concern about the relationship between iron stores and the severity of type 2 diabetes. In this study, we aimed to evaluate serum ferritin level among Mongolian individuals with and without diabetes. METHODS: Of 254 participants, a total of 99 previously diagnosed patients with type 2 diabetes and the same numbers of subjects without diabetes were enrolled and invited to a physical examination (BMI, central obesity, blood pressure) and fasting blood tests (fasting blood glucose, HbA1c , serum ferritin, C-reactive protein, aspartate aminotransferase, alanine transferase). RESULTS: Serum ferritin was higher in the patients with type 2 diabetes compared with the control group without diabetes, with a significant difference in the female groups (341.6 ± 67.2 and 159.1 ± 36.8 ng/ml respectively, P = 0.019). Of the patients with type 2 diabetes, 43.4% had hyperferritinaemia, and 21.2% of the individuals without diabetes had hyperferritinaemia. In the group with type 2 diabetes, serum ferritin level was significantly higher in the group of women whose HbA1c was ≥ 53 mmol/mol (7.0%) compared with the other group of women whose HbA1c was < 53 mmol/mol (7.0%) (562.1 ± 122.1 and 220.5 ± 78.7 ng/ml respectively, P = 0.025). We also found that the subjects without diabetes, aged over 55 years, are at risk of increased serum ferritin. CONCLUSION: Poorly controlled patients with type 2 diabetes and people without diabetes of over 55 years of age are likely to be at a higher risk of developing hyperferritinaemia. Thus, regular assessments of serum ferritin might be important for those who are at risk of hyperferritnaemia for prevention and an early intervention.

Tumor progression in hepatocellular carcinoma may be mediated by p53 mutation.

Human hepatocellular carcinoma (HCC) often contains intratumoral subpopulations of heterogeneous cellular differentiations within each tumor. To analyze the genetic alterations of p53 in the heterogeneous subpopulations, we examined 68 intratumoral nodular lesions within 34 HCCs composed of two distinct subpopulations. The cellular differentiations were determined histologically by Edmondson's grading system. Nine (26.5%) of 34 HCCs examined were found to have genetic alterations in exons 5 to 8 of the p53 gene, resulting in amino acid substitutions. Three of these nine HCCs with p53 mutations showed genetic heterogeneity of the p53 gene within each tumor; one HCC had a single missense mutation at codon 210 (asparginine to 210-serine) in an intratumoral lesion of Edmondson Grade II and double missense mutations at codons 210 and 217 (asparginine to 210-serine and valine to 217-alanine) in another intratumoral lesion of Edmondson Grade III. The remaining two HCCs had p53 mutations only in lesions of a higher grade. In total, the p53 mutations were detected in none of eight Edmondson Grade I lesions, in five of 29 Grade III lesions (17.2%), in eight of 26 Grade III lesions (30.8%), and in three of five Grade IV lesions (60.0%). Thus, our data revealed that the p53 mutations were closely related to the progression of HCC and that, in certain cases, malignant cells which acquired the p53 mutations might develop into dedifferentiated subpopulations within individual HCC.

Lack of intrahepatic recurrence of hepatocellular carcinoma by temporary portal venous embolization with starch microspheres.

Immediate recurrence in the hepatic remnant is sometimes evidenced after curative resection for treatment of hepatocellular carcinoma. One possible cause of this early recurrence is the multiple dissemination of tumor cells via the portal vein in the remnant liver as a result of surgical manipulations. In an attempt to prevent such recurrences, we performed ultrasonically guided, intraoperative portal embolization with starch microspheres in eight patients with hepatocellular carcinomas. These starch microspheres lodge only temporarily in the microvasculature, and there are no adverse effects, such as a rise in portal pressure or postoperative liver dysfunction. To date, there is no recurrence in any patient.

Possible transmission of serum hepatitis in liver surgery with the ultrasonic dissector.

When the ultrasonic dissector is used during liver surgery, the possibility exists of the transmission of virus to the attending hospital personnel because of unavoidable splashing of the irrigating solution. It becomes apparent from this study that the titer of hepatitis B surface antigen in the aspirated irrigating solution is almost the same level as that in the serum. We therefore strongly recommend that eye shields should be used in hepatic surgery when the ultrasonic dissector is in use.

Lack of preventive effect of branched-chain amino acid solution on postoperative hepatic encephalopathy in patients with cirrhosis: a randomized, prospective trial.

The purpose of this randomized, prospective study was to determine whether the infusion of branched-chain amino acid (BCAA)-enriched solution had a preventive effect for treating postoperative hepatic encephalopathy in patients with cirrhosis. Among the 56 patients with cirrhosis, 29 were given BCAA-enriched solution, and 27 were given the conventional amino acid solution for 14 days postoperatively. These groups were indistinguishable with regard to clinical and laboratory criteria at entry, except by sex. The molar ratio of BCAA to aromatic amino acids in the BCAA group was increased postoperatively, whereas the ratio in the control group was decreased, the difference being statistically significant. Among the 29 who received BCAA, three (10.3%) had hepatic encephalopathy; two died and one recovered. Of the 27 control patients, hepatic encephalopathy occurred in three (11.1%); one died and two recovered. There was no significant difference in rate of occurrence of hepatic encephalopathy between the groups. Thus the infusion of BCAA-enriched solution apparently had no preventive effect with regard to hepatic encephalopathy for patients with cirrhosis who underwent surgical treatment.

Postoperative mechanical ventilation preventing the occurrence of pleural effusion after hepatectomy.

To determine factors leading to pleural effusion after hepatectomy, the frequency of pleural effusion was investigated in 68 patients who underwent hepatic resection, with or without dissection of the right coronary ligament. In 36 of 44 patients (81.8%) who underwent hepatic resection with complete dissection of the right coronary ligament, and in two of 24 (8.3%) who underwent the procedure without dissection of this ligament, pleural effusion developed in the right hemithorax (p less than 0.001). Difference in pressure between the abdominal and thoracic cavities was considered to lead to ascites in the chest via the diaphragmatic triangular area (where there is no parietal peritoneum). While investigating the preventive effect of mechanical ventilation following hepatic resection on the occurrence of pleural effusion in 12 patients, we concluded that effusion could be prevented with use of mechanical ventilation--an approach that retained the intrathoracic pressure in a positive state.

Repeat hepatectomy for recurrent hepatocellular carcinoma.

BACKGROUND: The significance of repeat hepatectomy for recurrent hepatocellular carcinoma remains controversial. Therefore the aim of this study was to reevaluate both the survival and the surgical risks of repeat hepatectomy. METHODS: The significance of repeat hepatectomy including the survival and the surgical risks for recurrent hepatocellular carcinoma were investigated with 21 patients who underwent a curative repeat hepatectomy during the period between May 1975 and July 1993. For a comparison of survival, 253 patients who underwent a curative primary hepatectomy during the period between April 1985 and July 1993 were used. Moreover, the preoperative liver function tests were also compared between the first and second hepatectomies. RESULTS: Regarding the preoperative liver function tests, the indocyanine green dye excretion rate at 15 minutes in the second hepatectomy (18.7% +/- 8.7%) was significantly higher than that in the first hepatectomy (14.7% +/- 5.9%). With regard to the surgical risks, there was no difference in the clinical parameters for blood loss, operation time, and the incidence of postoperative complications between the first and second hepatectomies. The postoperative hospital stay for the second hepatectomies was relatively shorter than that for the first hepatectomies. In addition, the patient's survival and disease-free survival after a curative repeat hepatectomy were almost identical to that after a curative primary hepatectomy. CONCLUSIONS: A curative repeat hepatectomy is thus considered to be the most effective therapeutic modality for recurrent hepatocellular carcinoma.

Isolated hepatic caudate lobectomy.

BACKGROUND: Isolated caudate lobectomy is a challenging surgical procedure for which safe and reliable techniques have yet to be developed. METHODS: Isolated caudate lobectomy was performed by initial inflow control of the caudate lobe, full mobilization of the liver from the inferior vena cava by dividing all short hepatic veins, and parenchymal division dorsal to the major hepatic veins with a clockwise rotation of the liver while the liver was selectively devascularized by Pringle's maneuver and occlusion of the confluence of the major hepatic veins flush with the inferior vena cava. RESULTS: Two patients with cirrhosis underwent this procedure successfully without intraoperative hemodynamic instability or postoperative liver dysfunction. CONCLUSIONS: This technique allows safe and truly selective excision of the caudate lobe without the need for occlusion of the inferior vena cava or venovenous bypass.

Des-gamma-carboxy prothrombin and proliferative activity of hepatocellular carcinoma.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a useful marker for the prognosis of hepatocellular carcinoma (HCC). In this report we investigated the relationship between the positivity of DCP and proliferative activity of HCC and discuss the cause of poor prognosis of DCP-positive HCC. METHODS: Immunohistochemical and clinicopathologic study was done in 114 patients with resected HCC measuring less than 6 cm in diameter by using monoclonal antibody for proliferating cell nuclear antigen (PCNA). RESULTS: PCNA labeling index (PCNA-LI) was significantly higher in the patients with DCP-positive HCC than in those with DCP-negative HCC; also a positive correlation was noted between the PCNA-LI and the DCP level. We divided patients into two groups according to the PCNA-LI. In the high PCNA-LI group the patients with DCP-positive HCC exhibited a higher PCNA-LI than did the patients with DCP-negative HCC. As for pathologic prognostic factors, the DCP-positive high PCNA-LI group showed the highest incidence of tumor thrombus of the portal vein and intrahepatic metastasis while also exhibiting the lowest recurrence-freedom rate. From multivariate analysis we find that DCP, as well as PCNA-LI, is one of the risk factors for recurrence of HCC after hepatectomy. CONCLUSIONS: Our results thus suggest that DCP-positive HCC showed high PCNA-LI, and this might be the main cause for early intrahepatic spread and poor prognosis of DCP-positive HCC.

Graft replacement of pararenal inferior vena cava for leiomyosarcoma with the use of venous bypass.

Total replacement of the inferior vena cava across the renal vein confluence was successfully performed under venovenous bypass in a patient with primary leiomyosarcoma of the inferior vena cava. Concomitant resection of metastases by right nephrectomy, partial hepatectomy, and cholecystectomy allowed recurrence-free survival for the past 20 months. To the best of our knowledge, this is the first report of successful replacement of the inferior vena cava for a primary tumor.

Extracorporeal hepatic resection for previously unresectable neoplasms.

BACKGROUND: Some hepatic tumors are judged inoperable solely for anatomic reasons, such as the proximity of the tumor with the major vasculature. This is because of high mortality and morbidity rates, as well as a compromised surgical margin. METHODS: We successfully performed extracorporeal hepatic resections in two patients who were judged to have inoperable tumors by conventional means. RESULTS: Both patients had an uneventful postoperative course, and although one patient had intrahepatic recurrence 6 months after operation, the other patient shows no recurrence 10 months later. CONCLUSIONS: Advances in techniques for liver transplantation and organ preservation now allow resection of anatomically unresectable hepatic tumors that were deemed inoperable in the past.

Effect of diabetes mellitus on hepatic resection.

We evaluated the effect of diabetes mellitus on mortality and morbidity after elective hepatic resections. Of 209 patients who underwent hepatic resections between April 1985 and July 1990, 49 (23.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (75.5% vs 51.3%), mainly due to hepatic decompensation (55.1% vs 36.3%) and intraperitoneal sepsis (18.4% vs 6.3%). However, their incidence of hospital death (2% vs 2.5%), mean +/- SD postoperative hospital stay (36.1 +/- 20.2 days vs 29.4 +/- 28.2 days), and long-term survival were comparable with those of nondiabetics. Diabetics with and without complications were similar in preoperative or postoperative insulin requirement, duration of diabetes, and preoperative fasting glucose. Nevertheless, all eight patients with 24-hour urinary glucose excretion above 1 g developed complications. We conclude that diabetics are at a high risk of morbidity, but not of mortality after elective hepatic resection.

A new approach for liver surgery. Transdiaphragmatic hepatectomy for cirrhotic patients with hepatocellular carcinoma.

OBJECTIVE: To clarify the efficacy of transdiaphragmatic hepatectomy. DESIGN: Transdiaphragmatic hepatectomy and transabdominal hepatectomy were retrospectively compared. SETTING: This technique is used in cirrhotic patients with hepatocellular carcinoma located near the diaphragm. PATIENTS: Thirty-six cirrhotic patients with hepatocellular carcinoma who underwent transdiaphragmatic (group 1 [n = 8]) or transabdominal (group 2 [n = 28]) hepatectomies between April 1985 and March 1993 were investigated. All patients underwent a partial hepatectomy for hepatocellular carcinoma less than 3 cm in diameter located in segment VII or VIII or near the confluence of the hepatic veins. MAIN OUTCOME MEASURE: Intraoperative and postoperative clinical parameters, including operative time, blood loss, and length of hospital stay. RESULTS: The mean +/- SD operative time was significantly shorter in group 1 (184 +/- 25 minutes) than in group 2 (270 +/- 79 minutes). The intraoperative blood loss was significantly smaller in group 1 (857 +/- 622 mL) than in group 2 (1318 +/- 926 mL). The rate of postoperative complications was lower in group 1 (13% [n = 1]) than in group 2 (43% [n = 12]). The postoperative hospital stay was significantly shorter in group 1 (16 +/- 5 days) than in group 2 (23 +/- 16 days). CONCLUSIONS: Transdiaphragmatic hepatectomy is a useful technique for cirrhotic patients with hepatocellular carcinoma located near the diaphragm.

Simplified inflow control using stapling devices for major hepatic resection.

We describe the efficacy of a new technique for hepatic inflow division using stapling devices in major hepatic resections. We studied 28 consecutive patients who underwent major hepatic resection at a tertiary referral center by en masse inflow control of Glisson's pedicle in 1993 and 1994, of whom 10 underwent inflow control with stapling devices. Although stapling devices were used for larger tumors (mean +/- SD, 12.2 +/- 8.6 vs 5.7 +/- 5.0 cm; P = .02), the operation time (261 +/- 57 vs 301 +/- 143 minutes), operative blood loss (2071 +/- 1318 vs 4792 +/- 6586 mL), postoperative intra-abdominal bleeding (0% [0/10] vs 17% [3/18]), and hospital stay (16.0 +/- 2.6 vs 20.6 +/- 7.4 days) were favorable for resections with staplers vs resections without staplers; the overall incidences of postoperative complications (40% [4/10] vs 39% [7/18]) and hospital death (10% [1/10] vs 6% [1/18]) were comparable in the two groups. We conclude that stapling devices allow simple, quick, and safe en masse inflow control in major hepatic resections.

Liver resection for hepatocellular carcinoma in the elderly.

OBJECTIVE: To estimate the effectiveness of hepatic resection on hepatocellular carcinoma (HCC) in the elderly. DESIGN: Comparison with younger patients. SETTING: A municipal hospital and a large university hospital in Japan. PATIENTS: The study included 39 patients (age > or = 70 years [the elderly group]) and 229 patients (age < 70 years [the younger group]) who underwent hepatic resection from April 1985 to March 1993. The preoperative clinical features (Child's classification, association of cirrhosis and liver functions) were comparable between two groups. The positive rate for hepatitis C virus antibody was higher in the elderly group (88% vs 59%; P = .016). MAIN OUTCOME MEASURES: Morbidity and survival following operation and the pathological features of HCC. RESULTS: The incidence of postoperative hepatic failure was higher in the elderly group (10% vs 2%; P = .018). However, the incidence of operative death in the elderly group (5% vs 1%) as well as the incidence of other postoperative complications and rates of long-term survival (75.9% vs 51.6% at 5 years) and disease-free survival (30.4% vs 31.0% at 5 years) were similar to those in the younger group. The pathological features of HCC were identical between the two groups. CONCLUSION: The outcome of surgical treatment of HCC in the elderly group was satisfactory when compared with that in the younger group.

The role of prostaglandins in hepatic resection.

The role of prostaglandins (PGs) and the efficacy of PGE1 were investigated in hepatic resection. Patients who underwent hepatic resection were randomly assigned to two groups consisting of a control (n = 5) and a PGE1 treatment group (n = 6). Then the amount of 6-keto PF1 alpha, thromboxane B2 and (TXB2) and PGE2 were serially measured both before and after hepatic resection. Regarding changes in the PGs, a remarkable increase in TXB2 during hepatectomy was demonstrated in both groups. In the control group, both 6-keto PF1 alpha and PGE2 showed only a slight increase both during and after the operation. Regarding the efficacy of PGE1 on liver damage, no significant difference in postoperative liver function was found, however the lipoperoxide level at postoperative day 3 in the PGE1 treatment group (1.9 +/- 0.4 nmol/ml) was significantly lower than that in the control (2.6 +/- 0.5 nmol/ml: P < 0.05). Judging from the remarkable increase of TXB2, a stable metabolite of TXA2 during hepatectomy, it may be suggested that TXA2 plays an important role in the development of liver damage during hepatic resection.

Effect of nafamostat mesilate on coagulation and fibrinolysis in hepatic resection.

The effect of nafamostat mesilate on coagulation and fibrinolysis was investigated in a study of 22 patients with hepatocellular carcinoma who underwent a hepatic resection. The patients were divided into two groups: group 1, control (n = 11) and group 2, those with the intraoperative and postoperative use of nafamostat mesilate (0.2 to 0.4 milligram per kilogram per hour, n = 11). Nafamostat mesilate tended to suppress the coagulation expressed by thrombin-antithrombin III complex and fibrinopeptide A both during and immediately after operation. Moreover, nafamostat mesilate significantly suppressed the fibrinolysis expressed by euglobulin lysis activity both during and after operation. With regard to the initial stage of the fibrinolytic system, such as tissue-type plasminogen activator and plasminogen activator inhibitor-1, there was no difference between the groups. Therefore, the suppression of the euglobulin lysis activity may be caused by the inhibition of plasmin activity. There was no difference between the groups regarding operative blood loss. However, the rate of blood transfusion in group 2 was lower than that in group 1, and no fresh frozen plasma was required for the patients who lost over 2,000 milliliters of blood. Nafamostat mesilate can suppress euglobulin lysis activity both intraoperatively and postoperatively, and thus decrease the amount of blood transfusion needed. Therefore, at present, nafamostat mesilate seems to be one of the most useful agents for stabilizing the coagulant and fibrinolytic systems in hepatic resection.

Changes in regulating blood coagulation in hepatic resection with special references to soluble thrombomodulin and protein C.

The protein C anticoagulant pathway in hepatic resection was studied. The patients were divided into two groups--group 1 consisted of patients with a normal liver and group 2 consisted of patients with either hepatitic or a cirrhotic liver. Plasma protein C activity and soluble thrombomodulin were then sequentially measured during hepatectomy and in the early postoperative period. The protein C activity in group 1 decreased during hepatectomy and reached a low immediately after operation, and thereafter, recovered to near preoperative levels. However, the preoperative value in group 2 was lower than that in group 1 and the postoperative values were significantly lower than those in group 1 (p < 0.05). The level of soluble thrombomodulin in group 1 decreased during hepatectomy but later returned to preoperative levels. However, in group 2, the preoperative value was higher than that in group 1 and the postoperative values were greater than that of the preoperative values, while the values were significantly higher than those in group 1 (p < 0.05). During hepatectomy, hypercoagulability may contribute to the low levels of protein C and soluble thrombomodulin. The postoperative significant increase of soluble thrombomodulin may, thus, indicate the occurrence of endothelial injury in the remnant liver. The sequential measurements of both parameters can, therefore, be useful in detecting coagulopathy and endothelial injury in hepatic resection.

Modulation of coagulation and fibrinolysis in hepatic resection: a randomized prospective control study using antithrombin III concentrates.

A randomized prospective control trial for determining the efficacy of antithrombin III concentrates in hepatic resection was performed using 24 patients with hepatocellular carcinoma. Thirteen patients were given antithrombin III concentrates (1,500 IU) immediately before operation, during hepatectomy and immediately after operation. Coagulant and fibrinolytic profiles were determined by molecular markers such as thrombin-antithrombin III complex and plasmin-alpha 2plasmin inhibitor complex. During hepatic resection, both hypercoagulability and mainly primary hyperfibrinolysis occurred. Regarding the effectiveness of antithrombin III concentrates, in the antithrombin III treatment group, only a significant lower incidence of positive soluble fibrin monomer complex at postoperative days 1 and 5 was found among all the parameters studied. Therefore, no definite evidence of clinical usefulness of the perioperative administration of antithrombin III concentrates in hepatic resection was proved.

The difference in chemosensitivity to antineoplastic agents of human hepatocellular carcinoma cells under normo-oxygenated or hypoxic conditions.

In order to select more effective drugs under hypoxia for the treatment of hepatocellular carcinoma, the cytotoxicity of antineoplastic agents for two hepatoma cell lines, PLC/PRF/5 and HuH-7, was examined under both oxygenated and hypoxic conditions. Mitomycin C was observed potentially to have enhanced cytotoxicity under hypoxic conditions for both hepatoma cell lines. Carboquone showed enhanced cytotoxicity under hypoxia for PLC/PRF/5 alone. On the other hand, there was no cytotoxic enhancement of adriamycin or cisplatin in either cell line. Thus, the sensitivity of tumour cells to the cytotoxic agents altered according to the conditions to which the tumour was exposed. The selection of the antineoplastic drugs for chemotherapy therefore should depend not only on the sensitivity of individual tumours to various drugs, but the alteration of the cytotoxicity of the drugs under certain conditions should also be carefully taken into account.