Nobutaka Umekita

Prognostic value of concomitant resection of extrahepatic disease in patients with liver metastases of colorectal origin

BACKGROUND Operative resection is the treatment of choice for colorectal liver metastasis. In the present study, we investigated the prognostic factors after hepatic resection, focusing on the concomitant resection of extrahepatic metastases. METHOD A retrospective cohort study was performed in 187 consecutive patients who had undergone initial hepatic resections for colorectal metastases using the Cox proportional hazards model. RESULTS The overall survival rates at 3, 5, and 10 years were 49%, 30%, and 22%, respectively. Hilar lymph node involvement (HLN), localized peritoneal seeding (P), and distant organ metastasis (M) were resected in addition to the liver metastases in 9, 13, and 21 patients, respectively. The P and M factors were related univariately to an unfavorable patient prognosis, but the HLN factor was not. In a multivariate regression analysis, the hazard ratios of these three factors of interest were 1.58 (HLN; 95% confidence interval 0.64-2.52, median survival 48 months), 2.12 (P; 1.38-2.85, 18 months), and 3.07 (M; 2.45-3.68, 19 months), respectively. CONCLUSION Aggressive operative resection for colorectal liver metastases yielded an acceptable long-term outcome. The presence of distant organ metastasis seems to be a contraindication for operative intervention and/or resection; although the number of patients enrolled in the present study was small, resection of localized peritoneal seeding or hilar lymph node involvement, in addition to the resection of the liver metastases, may benefit patient survival.

Hepatic transport of indocyanine green in dogs chronically intoxicated with dimethylnitrosamine

Hepatic transport of indocyanine green (ICG) was examined in dogs chronically intoxicated with dimethylnitrosamine (DMN) (2 mg/kg) intraportally once a week for 6 weeks. In pathophysiological consequences, significant increases (p less than 0.05) were shown in both glutamic-pyruvic transaminase (GPT) and total plasma bile acids, but no significant difference was shown in body weight, liver wet weight, glutamic-oxaloacetic transaminase (GOT), plasma alkaline phosphatase activity, total plasma protein, and total plasma bilirubin. By histologic examination of livers from intoxicated dogs, increased fibrosis in periportal, perisinusoidal, and especially pericentral areas, with loss of normal architecture, was observed. Partial fibrous bridging between periportal and pericentral areas was also demonstrated, but extensive pseudolobulation with regenerative nodules was not observed. The portal venous pressure of the intoxicated dogs was increased by approximately 50% of that of control dogs. In intoxicated dogs, delays were shown in both plasma disappearance and biliary excretion of ICG and significant decreases were observed in the pharmacokinetic parameters k12 (plasma to liver transfer rate constant), V2 (distribution volume of liver compartment), and CLtot (total body-plasma clearance), while a significant increase was observed in k23 (intrahepatic diffusion and transport rate constant); the V1 (distribution volume of plasma compartment) was not altered. From these findings, it is suggested that the decrease in the intrinsic clearance of ICG for the hepatic uptake process might explain the decrease in ICG uptake rate into the liver which was observed in the DMN-intoxicated dogs. Dogs chronically intoxicated with DMN might be a good model for studying hepatic dysfunction.

Metachronous colonic metastasis from pancreatic cancer seven years post-pancreatoduodenectomy

Colonic metastasis from other organs is very rare. Here we report the case of a 62-year-old man with a history of pancreatoduodenectomy for stage IIB pancreatic head cancer performed seven years back. He presented with abdominal distension and pain. Under the preoperative diagnosis of bowel obstruction, surgical treatment was performed, and a circumferential lesion causing bowel obstruction of the ascending colon was detected. A right hemicolectomy with lymph node dissection was performed. The specimen showed a 5-cm wall thickening with a cobble-stone like appearance of the ascending colon, which morphologically appeared scirrhous. Histological examination revealed cancer nests invading from the subserosa to the muscular and submucosal layers of the colon. Immunohistochemical analysis of the tumor cells demonstrated positive staining for cytokeratin 7, but negative for cytokeratin 20, which was the same as the previous pancreatic cancer specimen. These pathological and immunohistochemical features strongly supported the diagnosis of colonic metastasis from the pancreas. Thereafter, the patient received systemic chemotherapy, but unfortunately, he died 14 mo after the surgery.

Hepatic extraction of chenodeoxycholic acid in dogs chronically intoxicated with dimethylnitrosamine.

The pharmacokinetics of chenodeoxycholic acid (CDCA) in hepatic dysfunction were evaluated by analyzing the plasma disappearance curves after simultaneous administration of [3H]- and [14C]-CDCA through the femoral and portal veins, respectively, in dogs chronically intoxicated with dimethylnitrosamine (DMN). The plasma concentration-time curve of intravenously administered [3H]-CDCA was best fitted to a three-exponential equation, while that of intraportally administered [14C]-CDCA was fitted to either a two- or a three-exponential equation. In the DMN-intoxicated dogs, significant decreases were observed in total body plasma clearance (CLp), hepatic extraction ratio (EH) and apparent intrinsic clearance (CLint) compared to those of the untreated (control) dogs. The hepatic blood flow (QH), calculated from CLp, CLint and blood-to-plasma concentration ratio (RB) according to the equation reported by Wilkinson and Shand [Clin. Pharmac. Ther. 18, 377 (1975)], was reduced to approximately 70% in the DMN-intoxicated dogs compared to the control dogs. The bindings of CDCA to plasma and liver cytosol fraction were determined by equilibrium dialysis; no significant difference was observed in the unbound fraction between the DMN-treated and control dogs. By comparing both pharmacokinetic parameters obtained from intravenous and intraportal administration, the usefulness of the oral bile acid tolerance test was examined. From these findings, it was suggested that the decrease in the CLp of the DMN-intoxicated dogs was due to both the decrease in QH and that in CLint, and that the decrease in CLint may be due not to an alteration of plasma or cytosol binding but to that of a carrier-mediated transport system. It is also suggested that the measurement of fasting plasma bile acid concentration or the oral bile acid tolerance test is more sensitive for the detection of hepatic dysfunction than the intravenous bile acid tolerance test.

Hepatocellular carcinoma with hepatic venous obstruction and hepatic venous collaterals.

via the mass ( fig. 2 ). A left hemihepatectomy was performed combined with resection of the distal part of the middle hepatic vein. The pathologic diagnosis was hepatocellular carcinoma, with tumor invasion of the adventitia of the resected part of the middle hepatic vein, without any endoluminal invasion. A hypervascular liver tumor causing obstruction of the hepatic veins with hepatic venous collaterals is usually a focal nodular hyperplasia, whereas hepatocellular carcinoma can also be associated with these vascular abnormalities as in the present case. Dynamic computed tomography of a 60-year-old man revealed a mass, 7 cm in diameter, in the left liver, which was high density in the early phase ( fig. 1 a), and isoto low density in the late phase ( fig. 1 b). The middle hepatic vein appeared compressed and obstructed by the mass, which was calculated from the following finding: in the early phase of volume-rendered coronal computed tomography, the right hepatic vein as well as the middle and the left hepatic veins were enhanced through the hepatic venous collaterals between the middle and the right hepatic veins due to the hepatic artery hepatic venous shunt Published online: October 1, 2008

Aberrant coronary vein as a hepatopetal collateral pathway for extrahepatic portal venous obstruction.

tor of the liver was identified as an aberrant coronary vein ( fig. 1 ). A superior mesenteric arterioportogram revealed portal vein obstruction, resulting in portal blood flowing back to the right gastroepiploic and splenic veins. Venous blood of the lesser curvature then drained into the left portal system via the aberrant coronary vein ( fig. 2 ). Cavernous transformation of the portal vein is a typical finding when the portal vein is obstructed with or without the intrahepatic branch. An aberrant coronary vein can be a hepatopetal collateral pathway when the portal vein is obstructed as in the present case. The coronary vein normally joins the portal vein, the splenic vein, or the confluence of the two. In contrast, persisting anastomoses among the foregut venous plexus or omphalomesenteric veins result in various venous anomalies, including the aberrant coronary vein, which originates from the lesser curvature of the stomach, moves through the lesser omentum and drains directly into the left portal system. Computed tomography of a 50-year-old man revealed a low density mass, 10 cm in diameter, in the retroperitoneal space behind the pancreas head. A thick vein from the lesser curvature that drained into the left lateral secPublished online: September 26, 2008

Experimental studies of pulmonary edema in portal hypertention.

門脈圧亢進症に合併する肺浮腫が門脈血内の血管透過性物質の体循環への流入による肺血管透過性の亢進によって起こるのかを検討するため,ラットでEck瘻を作成しA群:Eck瘻開存群(n=8)B群:Eck痩閉塞群(n=9)C群:Sham手術群(n=6)の各群にわけ肺血管外水分量を測定した.肺血管外水分量/体重(ml/kg)はA群:2.02±0.27, B群:2.33±0.41*C群:1.84±0.16でありA, B群で増加したが,B群においてのみ有意であった.B群は門脈圧亢進状態にあり,部分的な門脈体循環短絡を形成していると考えられ,門脈体循環短絡量はA群がB群より多量であると考えられるが,B群の方が肺血管外水分量の増加が大きかったことは肺血管の透過性の亢進には門脈体循環短絡の存在とともに門脈圧亢進状態がなんらかの形で関与しているものと推測された.