Treatment of advanced gastric cancer with 5-fluorouracil and cisplatin in combination with dipyridamole.

We investigated the efficacy of combination chemo-therapy using 5-fluorouracil (5-FU), cisplatin (CDDP), and dipyridamole (DP), which is based on the concept of double biochemical modulation. Twenty-eight patients with advanced gastric cancer were treated with the simultaneous continuous intravenous (i.v.) infusion of 5-FU (800 mg/m2/day) and DP (4 mg/kg/day), and i.v. infusion of CDDP (20 mg/m2/day) for 5 days. The cycles were repeated every 4 weeks. Twelve patients (43%) had a partial response (PR), while stable disease (NC) occurred in 13 patients (46%), and progression (PD) in 3 patients (11%). An improved performance status was observed in 20 patients (71%). The carcinoembryonic antigen (CEA) level was markedly decreased in 75% of the CEA-positive patients. Toxicity was acceptable. The mean steady state plasma concentration of total DP was 6.40.5 microM, which thus seemed adequate to potentiate the cytotoxicity of 5-FU. The treatment regimen described herein thus appears to be effective, safe and well tolerated by patients with advanced gastric cancer.

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.

Clinical efficacy of the stapled anastomosis in esophageal reconstruction.

We have clinically evaluated Russian and American stapling devices used for esophageal reconstruction and compared the results following stapled anastomosis with those following hand-sutured procedures, both performed by the same surgeon. With the Russian stapler, anastomoses performed in 17 patients with carcinoma of the thoracic esophagus resulted in only one (5.9%) anastomotic leak; in 12 hand-sutured anastomoses and in 11 anastomoses done with an American stapler, no anastomotic complication occurred. Thus, a long gastric tube with good blood supply is of paramount importance, and if the technical details of surgical stapling can be overcome, a stapled anastomosis appears to be as safe as a manual suturing for patients undergoing esophageal reconstruction.

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.

Hepatic recurrence not prevented with low-dosage long-term intraportal 5-FU infusion after resection of colorectal liver metastasis.

Seventeen patients with colorectal cancer metastatic to the liver underwent hepatic resection. For five we prescribed adjuvant therapy which included intraportal mitomycin C (MMC) and 5-fluorouracil (5-FU) and consecutive oral administrations of tegafur (N1-(2'-tetrahydrofuryl)-5-fluorouracil), in an attempt to reduce recurrences in the liver. Intraportal chemotherapy consisted of low-dosage, long-term 5-FU infusion, 40 days at 250 mg/day, and a 10 mg bolus injection of MMC at the start and the end of continuous 5-FU infusion. With regard to postoperative events in patients given the infusion therapy, there was no hepatotoxicity or hematologic toxicity, no mechanical complications and no pain or vomiting. Two of five patients given infusion therapy and six of 12 not given the therapy died within 5 years after surgery. There was recurrence in the liver in two patients given infusion therapy and in four not given the therapy. Although low-dosage, long-term intraportal chemotherapy is a safe treatment given hopefully to prevent hepatic recurrence, we found no beneficial effect.

Intraperitoneal administration of cisplatin and etoposide during surgery for patients with gastric cancer.

Intraperitoneal chemotherapy has been attempted to treat peritoneal seeding in patients with gastric cancer. In this study, 13 patients with far advanced gastric cancer were given a complex chemotherapy regimen, cisplatin and etoposide, intraperitoneally during surgery. Cisplatin and etoposide was given 100 mg/body (58-90 mg/m2) and 200 mg/body (115-180 mg/m2), respectively, before closing the abdominal wall. There was one operative death who had an unresectable gastric cancer and died due to respiratory insufficiency, probably related to the drugs. There were no critical side effects due to the drugs among patients who underwent gastrectomy. Postoperative complications encountered were 2 cases of leukopenia, 2 of vomiting, 2 of renal impairment and 1 of liver dysfunction. These complications were transient and limited. The median survival duration was 7.0 months in this study. Thus, intraperitoneal cisplatin and etoposide should be examined for clinical use in larger scale trials.

Laparoscopy-assisted surgery: a new technique for transhiatal esophageal dissection.

Esophageal dissection under laparoscopic monitoring is performed during total esophagectomy to treat patients with cervical esophageal carcinoma. Using this technique, a safe esophageal dissection can be made from the surrounding mediastinal tissues. Some of the disadvantageous consequences of a blunt dissection, including the blind maneuver, may thus be prevented and various intraoperative and postoperative complications may be avoided.

Abdominal ultrasonography reveals the perforation site of duodenal ulcers.

Regardless of whether or not the laparoscopic approach is used, the simple closure using an omental patch is considered to be preferable to other surgical therapies for a duodenal ulcer perforation. We used abdominal ultrasonography (US) to identify the perforation site of the duodenal ulcer. To our knowledge, this is the first report describing how the perforation site of duodenal ulcers can be identified using US. Three patients diagnosed with perforated duodenal ulcers based on abdominal computed tomography and abdominal radiographic findings were scheduled for surgery. Under general anesthesia, US demonstrated free air on the liver and a "fish-eye sign" when the anterior or lateral wall was perforated. We performed a simple closure using an omental patch through a skin incision measuring only 3 cm in diameter above the area showing the fish-eye sign. The postoperative recovery was no different from that seen when a laparoscopic approach is used at our hospital. Even though the laparoscopic procedure is still the surgical modality of choice, the US technique allows for a successful diagnosis without invasive examinations. We believe that most surgeons and/or radiologists should try to detect the fish-eye sign using US as the diagnostic modality of first choice if they suspect a duodenal ulcer perforation. This technique allows us to mark the perforation site accurately before surgery.

Major hepatic resection in patients with a prosthetic heart valve receiving anticoagulation treatment.

We experienced two patients with a prosthetic heart valve, who underwent hepatic resection for hepatoma while on anticoagulation therapy. Patients with a prosthetic heart valve have the following characteristics; an increased risk of thromboembolism due to diminished anticoagulation in the perioperative period, a greater risk of endocarditis due to the artificial material in the heart, and impaired cardiopulmonary function including possible arrhythmia and heart failure. Furthermore, when such patients also have liver cirrhosis with a hepatoma, there is an increased risk of perioperative bleeding while on anticoagulation due to coagulopathy and also a risk of infection due to decreased cellular immunity. Patients with a prosthetic heart valve therefore require special care and attention whenever they have to undergo hepatic resection. With respect to anticoagulation, a minimal level is required to prevent bleeding and thromboembolism. Warfarin being administered preoperatively may be switched to heparin while closely monitoring the activated clotting time (biomaterial valve: 130-150 sec, non-biomaterial valve: 150-180 sec); the heparin should then be changed back to warfarin immediately after starting oral intake following operation. For the prevention of infection, a broad spectrum antibiotic should be used prophylactically both intra-operatively and postoperatively. The cardiopulmonary function must also be carefully monitored. For the assessment of postoperative liver function, lecithin: cholesterol acyltransferase, serum bilirubin and albumin are useful because there is no relevance of coagulation parameters such as prothrombin time under anticoagulation.

The role of prostanoid in hepatic damage during hepatectomy.

BACKGROUND/AIMS: The aim of this study in hepatectomy is to investigate whether or not hepatic ischemia elevates the serum prostanoid levels, and whether or not thromboxane A2 (TXA2) synthetase inhibitor (OKY 046) improves hepatic damage. MATERIALS AND METHODS: The prostanoid levels were measured in 22 hepatectomy cases. The beneficial effects of thromboxane A2 synthetase inhibitor were examined in cases who underwent hepatectomy under hemihepatic vascular control. The total prostanoid levels (6-keto PG Fla+ PGE2 + TXB2) were measured in 22 cases before and after hepatectomy. The hepatic ischemic time (HIT) was defined as the time required to perform a hepatic mobilization plus the right hemihepatic vascular control technique. RESULTS: The total prostanoid levels increased after hepatectomy (P < 0.01). The changes in the total prostanoid levels positively correlated with the HIT (P < 0.01). The 17 cases who underwent hepatectomy with the HIT were randomly divided into 2 groups; the OKY group (n = 9), OKY 046 (0.2 mg/kg/hr), the control group (n = 8); no drug was given. The OKY 046 administration reduced the TXB2 levels (P < 0.01), without any changes in the PGE2, or 6-keto PGF1a levels. The serum glutamic oxaloacetic transaminase levels after operation were lower, and the hepaplastin tests were higher in the OKY group than those of the control (P < 0.05). CONCLUSION: These results demonstrated that hepatectomy under ischemia elevated the prostanoid levels. OKY 046 significantly reduced the TXB2 levels and the degree of hepatic damage in hepatectomy under ischemia.

Laparoscopic splenectomy: the latest modern technique.

BACKGROUND/AIMS: Recent advances in technical instruments have resulted in increased safety and simplicity in laparoscopic surgery. The purpose of this article is to introduce our latest operative techniques for laparoscopic splenectomy. METHODOLOGY: The patient is placed in the right semidecubitus position and the gastrosplenic ligament including the short gastric vessels was performed by using an ultrasonically activated scalpel. The splenic artery and vein were resected at the splenic hilum with an autosuture device. The electromechanical morcellator was used to remove the spleen. RESULTS: The laparoscopic splenectomy was successfully performed in all 74 patients from 1992-1997. There was no deaths related to the operation. Conversion to open surgery with a small incision of 5 cm was required in one patient with advanced liver cirrhosis and portal hypertension and 45 patients with portal hypertension. CONCLUSIONS: A laparoscopic splenectomy is considered to be a safe and feasable modality for the treatment for hematologic disorders of both the spleen and other benign tumors.

A quick and simple technique for selective control of hepatic arterial bleeding.

A quick and simple technique for the selective control of hepatic arterial inflow is described for hepatic resections or hepatic hilar lymph node dissection which allows arterial hemostasis without causing splanchnic congestion.

Cytokine patterns and the effects of a preoperative steroid treatment in the patients with abdominal aortic aneurysms.

BACKGROUND: The aim of this study was to investigate the cytokine patterns of patients with abdominal aortic aneurysms and the effects of preoperative steroid administration on surgical stress. METHODS: From January 1996 to August 1996, 20 consecutive patients underwent an elective reconstruction of infrarenal abdominal aortic aneurysms. The patients were randomly divided into two groups consisting of a control group (n=10) and a steroid group (n=10), in whom 1 g of methylprednisolone was intravenously administered two hours before the operation. MEASURES: Interleukin-6 was serially measured and the perioperative parameters including C-reactive protein were compared between both the control and the steroid groups. RESULTS: The interleukin-6 values in the steroid group immediately after declamping, as well as at one and three postoperative days were significantly lower than those in the control group. C-reactive protein values at one postoperative day in the steroid group were also significantly lower than those in the control group. In one patient with a ruptured abdominal aortic aneurysm, the interleukin-6 values were higher than those in the patients undergoing elective surgery throughout the study. CONCLUSIONS: These results thus suggest that preoperative steroid administration using methylprednisolone in patients with abdominal aortic aneurysms appears to reduce surgical stress by decreasing cytokine release.

A simultaneous resection of a concomitant abdominal aortic aneurysm and hepatocellular carcinoma: two cases.

We report two cases of simultaneous surgical treatment in patients with a concomitant abdominal aortic aneurysm (AAA) and hepatocellular carcinoma (HCC). The first patient underwent abdominal echography and was observed to have an abnormal hepatic mass. A consecutive computed tomographic (CT) scan showed an AAA, measuring 8 cm in size. The hepatic mass, which reached 5 cm in size, existed in the S5 and was strongly suspected to be HCC. The second patient was observed to have AAA by CT scan three years ago and also shown to have a hepatic mass, which reached 3 cm in size, in the S8. Both patients underwent a simultaneous resection. At first, a resection and reconstruction of the aneurysm was performed, followed by an extended right lobectomy and anterior segmentectomy of the liver. The postoperative course was uneventful and they were discharged on the 29th and 22nd postoperative day. To our knowledge, this is the first report of patients who underwent a successful simultaneous resection of an AAA and HCC.

[Surgery for upper gastrointestinal diseases in cirrhotic patients].

Outcomes of surgery for gastric cancer or esophageal cancer in cirrhotic patients are not favorable. The preoperative assessment of liver function utilizing Child's classification or indocyanine green (ICG) excretion test can be a predictive factor of postoperative mortality. Operative risk is acceptable if patients are classified as Child's class A, and surgical procedures should be avoided in patients either classified as Child's class C or having ICG-R15 of 25% or more. To avoid postoperative complications, it is important to minimize the operative procedure and to ligate vessels instead of using electrocautery. Surgical stress and risk can further be reduced by a two stage operation for esophageal cancer and by gastrectomy with reduced lymph node dissection of D1 for gastric cancer. However, because curability of existing cancer is also required for surgical procedures, the status of liver cirrhosis and the stage of cancers should be considered in surgical treatment of gastric cancer or esophageal cancer in patients with liver cirrhosis.

Rapid normalization of portopulmonary hypertension after living donor liver transplantation.

Portopulmonary hypertension (PPHTN) is a relatively rare complication of end-stage liver disease, and a serious problem in the context of liver transplantation. Herein we have reported a case of decompensated liver cirrhosis with PPHTN, which rapidly resolved after adult-to-adult living donor liver transplantation (LDLT). A 54-year-old man was referred to our hospital with end-stage liver cirrhosis owing to chronic hepatitis C. Preoperative mean pulmonary artery pressure (mPAP), as assessed by right heart catheterization, was 38 mm Hg. Continuous infusion of epoprostenol decreased the mPAP to 24 mm Hg over 44 days. He underwent LDLT using a right hepatic lobe graft donated by his son. The postoperative course was uneventful, epoprostenol was weaned by postoperative day (POD) 21, and the mPAP normalized to 21 mm Hg on POD 28. The patient was discharged on POD 31 without any vasodilators. Our case revealed that liver transplantation can rapidly resolve PPTHN.

Biliary tract reconstruction in liver transplantation.

Biliary tract complications are often referred to as the "Achilles' heel" of liver transplantation and various techniques have been developed to overcome them. The two major methods of bile duct reconstruction currently in use consist of either (1) choledochocholedochostomy over a T-tube or, when duct-to-duct approximation is not feasible, choledochojejunostomy over an internal stent, or (2) interposition of the donor gallbladder as a conduit between the donor bile duct and either the recipient bile duct or a jejunal loop. Although these standardizations of biliary tract reconstruction have resulted in a reduction of biliary complications after liver transplantation, further advancement in the elucidation of ampullary obstruction and viability of the donor bile duct is needed.

Can hepatic failure after surgery for hepatocellular carcinoma in cirrhotic patients be prevented?

To study the causes of postoperative hepatic failure in cirrhotic patients undergoing resection for hepatocellular carcinoma, we evaluated data on 126 cirrhotic patients surgically treated from 1977 to 1987. The records of 102 patients with a good postoperative course (survival group) and 24 patients who developed hepatic failure and died (hepatic failure group) were reviewed. No difference in preoperative liver function was apparent between the 2 groups. Histologically, moderate to severe inflammatory activity in the liver was present in 20 (83%) of 24 patients in the hepatic failure group. Major hepatic resections (lobectomy and extended lobectomy) were more frequent in the hepatic failure group. Mean perioperative blood loss was 1,945 g and 4,322 g in the survival and hepatic failure groups, respectively, with a significant difference (p less than 0.01). Major postoperative complications occurred in 22 (22%) of 102 patients in the survival group and major complications followed by hepatic failure occurred in 21 (88%) of 24 patients in the hepatic failure group, with a significant difference (p less than 0.001). In light of these data, we propose that: (a) histological examination should be done before the resection, (b) perioperative blood loss should be less than 2,000 g, and (c) intensive care is needed postoperatively to prevent complications which might lead to hepatic failure.