Kazushi Nishio

Significant influence of accompanying chronic hepatitis status on recurrence of hepatocellular carcinoma after hepatectomy. Result of multivariate analysis.

OBJECTIVE The aim of this study was to evaluate the correlation between the histologic status of accompanying chronic hepatitis and the recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy by multivariate analysis. SUMMARY BACKGROUND DATA Recent studies have suggested that a considerable number of intrahepatic recurrence of HCC after hepatectomy might be the results of metachronous multicentric hepatocarcinogenesis. The authors hypothesized that the incidence of recurrence due to metachronous multicentric hepatocarcinogenesis would depend on the histologic status of accompanying chronic viral liver disease, which is a main promoter of HCC. METHODS One hundred ten patients with HCC who underwent curative resection were studied. Histologic status of accompanying chronic hepatitis was classified into the three categories: 1) normal liver or chronic persistent hepatitis (CPH, n = 13), 2) chronic aggressive hepatitis (CAH, n = 50), and 3) liver cirrhosis (LC, n = 47). RESULTS The Cox multivariate proportional hazard model showed that the accompanying chronic viral hepatitis status (p = 0.0133), extent of hepatectomy (p = 0.0078), and number of tumors (p = 0.0475) were significantly predictive variables for recurrence-free survival. By the log-rank test, recurrence-free survival rate in patients with CPH was significantly higher than those in patients with CAH (p = 0.0005) and LC (p = 0.0075). Patients with CAH had the lowest recurrence-free survival rate (vs. LC, p = 0.028). CONCLUSIONS The results of this study indicated the significant influence of histologic activity of hepatitis on recurrence of HCC. This might support the concept of significant contribution of multicentric hepatocarcinogenesis to recurrence of HCC after hepatectomy.

Pattern of Recurrence after Resection for Intraductal Papillary Mucinous Tumors of the Pancreas

Abstract. The objective of this study was to clarify the patterns of recurrence and prognosis after resection of intraductal papillary mucinous tumors (IPMTs). Fourteen patients with IPMT were reviewed histologically; intraductal papillary adenocarcinoma was present in 12 cases and intraductal papillary adenoma in 2. Six patients were alive with no evidence of disease. Two patients died from other causes. Six patients had recurrences. The median survival time was 46 months. In the six recurrent cases, the median postoperative disease-free interval was 38 months. Four patients died of recurrence, and the median survival time after recurrence was 6 months. The major site of recurrence was the remnant pancreas. The other sites were the liver in two cases, peritoneum in two, and local in one. These results suggest the multicentric or metachronous oncogenesis of IPMT. Because of the low frequency of lymph node metastases, an operation to preserve pancreatic function may be recommended, especially for localized tumors such as the branch type. It is important to avoid an incomplete resection using intraoperative pancreatoscopy and ultrasonography. Long-term follow-up after surgery is necessary even for a curative resection. We should perform total pancreatectomy for recurrences without distant metastases.

Serum Interleukin-6, Interleukin-8, Hepatocyte Growth Factor, and Nitric Oxide Changes during Thoracic Surgery

Abstract. Thoracic surgery creates a different environment from abdominal surgery in respect to the surgical procedure with pulmonary collapse under unilateral ventilation. Definitive evidence whether surgical trauma during thoracotomy is involved in postoperative pulmonary infections has not been clearly demonstrated. The objectives of this study were to evaluate the influence of surgical trauma during thoracotomy on postoperative infections and to investigate the clinical significance of postoperative humoral mediators in pulmonary infections after surgery. We measured serum interleukin-6 (IL-6), IL-8, hepatocyte growth factor (HGF), and nitric oxide (NO) levels in 27 patients undergoing thoracic surgery; the measurements were before and during thoracotomy, 60 minutes after reinflation, and after surgery. The patients were divided into three groups: lobectomy patients (group A), and esophagectomy patients without (group B) or with (group C) postoperative infections. The serum IL-6 and IL-8 levels in group C were markedly elevated 60 minutes after reinflation and were significantly higher than those in group A. The serum IL-8 levels during that period in group C were significantly higher than those in group B. The postoperative serum IL-6, IL-8, HGF, and NO levels were significantly higher in group C than in group B. Taken together, intraoperative hypercytokinemia, especially IL-8, following the thoracic procedure and subsequent reinflation preceded the clinical onset of postoperative infections. Hence postoperative serum IL-6, IL-8, and HGF levels may be useful predictors of infection after esophagectomy.

Repeat Hepatectomy for Recurrent Colorectal Metastases

Abstract. Recurrence rates after hepatic resection in patients with colorectal metastases are reported to range from 47% to 80%. Hepatic recurrence is seen in 35% to 50% of patients. Aggressive surgical resection appears to be a worthwhile treatment in patients with recurrent hepatic metastases to promote longer patient survival because surgical resection remains the only curative therapy available. This is a retrospective review of our experience with 15 patients undergoing repeat hepatic resection culled from 67 patients undergoing initial hepatectomy for metastatic colorectal cancer. Of 67 patients who underwent hepatectomy for colorectal hepatic metastases, 33 developed hepatic recurrence at a median interval of 23 months (range 1–176 months) after the first hepatectomy. The second hepatectomy was performed in 15 patients 5 to 29 months after the first hepatectomy, with no mortality. The mean operating time and blood loss at the second hepatectomy were similar to those at the first hepatectomy. The mean hospital stay at the second hepatectomy was significantly shorter than that at the first hepatectomy. The cumulative survival rate for the 15 patients was 42.4% at 3 years and 21.2% at 5 years, respectively, which compared favorably with the survival rate of the 67 patients who underwent initial hepatectomy. Patients who underwent the second hepatectomy had significantly higher survival rates from the first hepatectomy than the 18 patients with unresectable hepatic recurrence. Repeat hepatectomy can be performed safely and provides long-term survival rates similar to those of first hepatectomies. In appropriately selected patients, repeat hepatectomy for colorectal metastases is a worthwhile treatment.

A new evaluation of pancreatic function after pancreatoduodenectomy using secretin magnetic resonance cholangiopancreatography

BACKGROUND The remnant pancreatic function after pancreatoduodenectomy influences greatly postoperative quality of life. However, it has been difficult to evaluate the exocrine remnant pancreatic function postoperatively. The aim of this study was to assess the usefulness of secretin-stimulated magnetic resonance cholangiopancreatography (secretin MRCP) in evaluating the remnant pancreatic function and ascertaining the anastomotic patency after pancreatoduodenectomy. METHODS Thirty-four patients who underwent pancreatoduodenectomy were evaluated with secretin MRCP. The results of MRCP were determined by the amount of exocrine pancreatic secretion, and were graded as follows: grade I (poor secretion), grade II (moderate secretion), and grade III (good secretion). RESULTS Secretin MRCP could visualize the pancreatic secretion dynamically. MRCP grades were grade I in 11 patients, grade II in 12, and grade III in 11. There was a significant correlation between MRCP grade and glucose tolerance. We confirmed visually the patency of the anastomotic site in 24 patients (71%). MRCP grades correlated significantly with clinical symptoms. CONCLUSION Our results demonstrated secretin MRCP was feasible for evaluating the remnant pancreatic function after pancreatoduodenectomy.

Hyperthermo-Chemo-Hypoxic Isolated Liver Perfusion for Hepatic Metastases: A Possible Adjuvant Approach

As a possible intraoperative adjuvant approach to treating hepatic metastases we developed a method of hyperthermo-chemo-hypoxic isolated liver perfusion in combination with hepatic resection. This method was applied to 11 patients with colorectal hepatic metastases between 1992 and 1995. One patient died on postoperative day 14 of hepatic failure (9% mortality), the cause of which was live temperature that reached 42.9 degree C, which seems to be the maximum limit for thermal toxic effect on the human liver. The other 10 patients tolerated the perfusion well, with mild hepatic and non systemic toxicity after minor or even major hepatic resection; the serum aminotransferase and total bilirubin levels returned to normal levels by postoperative day 14. Only one of eight patients (13%) for whom cytotoxic drugs were added to the perfusate (mitomycin C 10 micrograms/ml or cisplatin 2 micrograms/ml) had hepatic recurrence by 19 months after the perfusion (mean follow-up 25.8 months; median 23 months; range 8-57 months). Two patients were alive with no evidence of disease at 13 and 57 months, respectively after the perfusion; the other five patients had postperfusion extrahepatic recurrences (median: 19 months; range 7-20 months). In contrast, hepatic metastases recurred 7 and 20 months after the perfusion, respectively, in the two patients not given a cytotoxic drug.

Predominant role of local immunosuppressive effect in enhanced efficacy of liposomal FK506 in organ transplantation

Liposomal FK506 is a new formulation of FK506 that increases FK506 levels in the liver and decreases them in the kidney in comparison to conventional IV formulation. In the present study, the efficacy of liposomal FK506 was evaluated in canine kidney and liver transplantation models. Liposomal FK506 increased the immunosuppressive efficacy of FK506 in the liver transplantation model, but decreased it in the kidney transplantation model. These results suggest that local immunosuppressive effects with increased intragraft FK506 level would play an important role in enhancing the immunosuppressive efficacy of liposomal FK506 in liver transplantation.

Agarose-microeneapsulated Islet Xenotransplantation.

Discordant異種膵ラ島移植におけるアガロースマイクロカプセル化 (MC (+)) と15-Deoxyspergualin (DSG) 投与の併用効果につき検討した.雑種成犬単離ラ島を5%アガロースハイドロゲルにて, マイクロカプセル化した.6,000個膵ラ島を糖尿病BALB/cマウス, またはNODマウスの腹腔内に異種移植した.Mc (+) ラ島の平均生着日数はそれぞれ37.8日, 30.6日であり, Mc (-) 群に対し有意の生着延長効果を認めた.Mc (+) に少量のDSG投与を加えることにより, 平均生着日数は76.3日, 75.3日とさらに著明に延長した.Mc (+) 群のマウス抗イヌ抗体価レベルは, DSG投与の有無にかかわらず, 移植後50%以上となる場合も認めたが, 正常血漿糖濃度が維持され, 抗体はMc (+) ラ島に傷害をあたえなかった.アガロースマイクロカプセル化とDSG投与の併用による著明な生着延長効果を認め, 将来の異種ラ島移植におけるバイオ人工膵の有用性を示した.