Yoshihiro Yokoi

Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma.

The clinicopathological characteristics relevant to prognosis after surgical treatment of intrahepatic cholangiocarcinoma (ICC) remain unclear. In this study, the clinicopathological features of 19 patients with mass-forming ICC, the most common form of the disease, were reviewed to analyze prognostic determinants. Two or more segmentectomies of the liver with systematic lymphadenectomy were performed in 18 patients. Resection of the extrahepatic bile duct was performed in 14 patients, and reconstruction of the portal vein was accomplished in 5 patients. Stage IVA or IVB tumors were seen in 13 patients, and lymph node (LN) metastasis was present in 14 patients. The estimated 5-year survival rate after surgery for mass-forming ICC was 28%, with median survival time of 18 months. In univariate analysis, five variables were determined to be significantly correlated with poor survival of patients with mass-forming ICC after surgery. These variables include mass-forming ICC with periductal infiltration, perineural invasion, portal vein invasion, presence of intrahepatic metastasis, and two or more LN metastases. Survival rates of 5 patients without LN metastasis and 6 patients with a single LN metastasis were 80% and 33% at 5 years, respectively, while 8 patients with two or more LN metastasis failed to survive beyond 2 years. Multivariate analysis revealed the presence of intrahepatic metastasis to be an independent prognostic factor of poor survival. Hepatectomy with resection of the extrahepatic bile duct and systematic lymphadenectomy yields a good chance for prolonged survival for patients with mass-forming ICC when the lesion is singular and LN metastasis is limited to a regional LN. Because the presence of intrahepatic metastasis was closely related to a poor prognosis in patients with mass-forming ICC, efficacious chemotherapy would be needed to control development of the lesion.RésuméLes caractéristiques clinicopathologiques influençant le pronostic après traitement des cholangiocarcinomes intra-hépatiq.ues (CIH) ne sont pas claires. Dans cette étude, les caractéristiques clinicopathologiques chez 19 patients porteurs de CIH à forme tumorale, la forme la plus fréquente, ont été analysés à des fins pronostiques. On a réalisé une segmentectomie de deux segments ou plus avec lymphadénectomie systématique chez 18 patients, une résection des voies biliaires extra-hépatiques chez 14 et une reconstruction de la veine porte chez 5 patients. Treize patients avaient une tumeur stade IVA ou IVB; 14 avaient des métastases ganglionnaires. La survie à 5 ans après chirurgie pour CIH à forme tumorale a été de 28%; la médiane de survie a été de 18 mois. En analyse univariée, on a trouvé cinq variables significativement associées à une survie médiocre chez les patients opérés de CIH à forme tumorale. Ces variables sont un CIH avec infiltration péricanulaire, un envahissement perineural, un envahissement portai, la présence de métastases hépatiques, et des métastases de deux ganglions ou plus. La survie de cinq patients sans métastase ganglionnaire et de six patients avec une seule métastase ganglionnaire ont été, respectivement, de 80% et de 33% à 5 ans, alors qu’aucun des huit patients avec deux métastases ganglionnaires ou plus n’a survécu au-delà de deux ans. En analyse multivariée, la présence de métastases intrahépatiques était un facteur indépendant de mauvais pronostic. Une hépatectomie avec résection des voies biliaires extra-hépatiques associée à un curage lymphatique systématique améliore les chances de survie prolongée en cas de CIH à forme tumorale lorsque la lésion est unique et les métastases ganglionnaires sont limitées à un seul ganglion lymphatique régional. Puisque la présence de métastases intrahépatiques est étroitement en rapport avec un mauvais pronostic chez les patients porteurs de CIH à forme tumorale, une chimiothérapie efficace est nécessaire pour contrôler l’évolution.ResumenTras el tratamiento quirúrgico, las características clínicopatológicas pronósticas más importantes para los pacientes con colangiocarcinomas intrahepáticos (ICC) son poco conocidas. En este estudio se revisan las características clínicopatológicas más frecuentes en 19 pacientes con grandes tumores ICC, con objeto de determinar los factores pronósticos más importantes. 18 casos fueron tratados mediante dos o más segmentectomías hepáticas y linfadenectomía sistemática. En 14 pacientes se procedió a la resección y subsiguiente reconstrucción de la vía biliar extrahepática y en 5 de la vena porta. 13 pacientes pertenecían al estadio IV A o IV B y adenopatias metastásicas (LN) se registraron en 14 enfermos. Tras el acto quirúrgico el porcentaje medio estimado de supervivencia a los 5 años fue del 28%, con un tiempo de supervivencia de 18 meses. En pacientes con ICC que cursan con una tumoración macroscópicamente visible y palpable, el análisis univariante detectó 5 variables significativas por lo que a la escasa supervivencia se refiere: tumoración ICC con infiltración periductal, invasión perineural o de la vena porta, existencia de metástasis intrahepáticas y 2 o más adenopatías (LN) metastásicas. La supervivencia a los 5 años de 5 pacientes sin metástasis ganglionares (LN) y con una sola adenopatía metastásica fue del 80% y 33%, mientras que 8 pacientes con dos o más adenopatias metastásicas (LN) no sobrevivieron más de 2 años. El análisis multivariante demostró que las metástasis intrahepáticas constituyen un factor pronóstico independiente, de escasa supervivencia. La hepatectomía con resección de la vía biliar extrahepática asociada a una sistemática linfadenectomia puede, con suerte, prolongar la supervivencia de pacientes con tumores ICC palpables, cuando la tumoración es única y las adenopatias metastásicas son exclusivamente regionales. Dado que la presencia de metástasis intrahepáticas es signo de mal pronóstico, se precisa una eficaz quimioterapia para controlar el desarrollo de este tumor.

Hepatic release of endothelin-1 after warm ischemia. Reperfusion injury and its hemodynamic effect.

This study investigated the release of endothelin (ET)-1 from the liver after warm ischemia/reperfusion (I/R) injury. Wistar rats were subjected to 120 min of warm hepatic ischemia by clamping the hepatic hilum under porto-jugular shunting. Reperfusion was performed by unclamping. The rats were divided into 2 groups receiving intravenous treatment with an anti-ET-1 mAb before ischemia (AET group) and with mouse immunoglobulin G (sham group). Hepatic blood flow was assessed by laser-Doppler flowmetry and reflectance spectrophotometry and was compared between the 2 groups along with the bile flow rate. The ET-1 concentrations of hepatic venous and portal blood were determined in the sham group, and the portal blood endotoxin levels were assayed in both groups. Both groups developed transient hypotension after reperfusion, but hepatic blood flow subsequently showed a significant improvement in the AET group. Hepatic congestion was detected in the sham group by both reflectance spectrophotometry and histological examination. After reperfusion, bile flow was significantly greater in the AET group. The portal endotoxin concentration showed no increase in both groups, and the hepatic venous blood ET-1 level in the sham group was significantly higher until 3 hr after reperfusion compared to the portal blood level. The 30-day survival rate was 50% in the AET group, whereas all the sham rats died within 12 hr. ET-1 was released from the liver after I/R injury and apparently participated in systemic and local hemodynamic changes that affected survival.

Appraisal of surgical treatment for pT2 gallbladder carcinomas.

This retrospective study was designed to appraise the surgical procedures for pT2 gallbladder (GB) carcinomas. Twenty patients with pT2 GB carcinomas underwent surgical resection. Hepatectomy of segments 4b and 5 was performed in 19 patients, and an extended right hepatic lobectomy was performed in 1. The extrahepatic bile duct was preserved in 8 patients in whom the disease was limited to the GB fundus and/or body. Regional lymphadenectomy was performed in 18 patients. A separate radical second operation was performed in 8 patients after cholecystectomy. Final pathological staging was stage IB in 15 patients, IIB in 4, and IV in 1. Overall 5-year survival rate in those 20 patients was 77% without operative deaths. The 5-year survival rate in 5 patients with nodal metastasis and in 8 patients without extrahepatic biliary resection was 80% and 100%, respectively. A separate radical second operation in 8 patients yielded 75% survival after 5 years. Perineural invasion as a prognostic determinant was closely associated with tumor extending to the neck or the cystic duct. Partial hepatectomy, usually with extrahepatic biliary resection and regional lymphadenectomy, was appropriate as a standard radical operation for pT2 GB carcinoma, but preservation of extrahepatic bile duct is advocated for disease limited to the GB fundus and/or body. Radical second operation enhanced the chance for cure in patients with pT2 GB carcinoma.RésuméCette étude rétrospective évalue les procédés chirurgicaux dans le traitement des cancers de la vésicule biliaire pT2. Vingt patients porteurs de tumeur de la vésicule biliaire pT2 ont eu une résection chirurgicale. L’hépatectomie des segments 4b et 5 a été réalisée chez 19 patients et une lobectomie droite étendue chez un. La voie biliaire extrahépatique a pu être préservée chez huit patients lorsque la maladie était limitée au fundus et/ ou au corps de la vésicule. Une lymphadénectomie régionale a été réalisée chez 18 patients. Une intervention radicale a été réalisée chez huit patients à distance de leur cholécystectomie initiale. Le staging anatomopathologique final a été stade « IB » chez 15 patients, stade « I1B » chez quatre, et stade « IV » chez un. Le taux de survie globale à 5 ans chez les 20 patients a été de 77%, sans aucune mortalité opératoire. Les taux de survie à 5 ans chez les cinq patients porteurs de métastases ganglionnaires et chez les huit patients sans résection extrahépatique, ont été, respectivement, de 80% et de 100%. En cas de deuxième intervention radicale, à distance, chez huit patients s’est soldée par une survie à 5 ans de 75%. L’envahissement périneural a été le facteur pronostique déterminant pour les tumeurs s’étendant au col vésiculaire et au canal cystique. L’hépatectomie partielle avec résection extrahépatique et une lymphadénectomie régionale ont été considérées comme l’intervention standard radicale en cas de tumeur pT2 mais la préservation de la voie biliaire extra-hépatique est conseillée en cas de cancer limité au fundus et/ou corps. L’intervention à distance radicale augmente les chances de cure chez le patient porteur de cancer pT2 de la vésicule biliaire.ResumenSe efectúa un estudio retrospectivo para averiguar el tratamiento quirúrgico realizado en carcinomas pT2 de vesícula biliar (GB). 20 pacientes con carcinomas pT2 de vesícula biliar (GB) fueron tratados quirúrgicamente. En 19 pacientes se efectuaron hepatectomías de los segmentos 4b y 5 y en 1 una lobectomía hepática derecha ampliada. La vía biliar extrahepática se conservó en 8 pacientes en los que la lesión estaba localizada, exclusivamente, en el fundus o cuerpo de la vesícula biliar. Iinfadenectomía regional se realizó en 18 casos. Fueron reintervenidos con criterios más radicales 8 pacientes tras sufrir una colecistectomía previa. La estadificación registrada fue la siguiente: estadio IB (n = 15) IIB (n = 4) y IV (n = 1 ). En los 20 pacientes la supervivencia global a los 5 años fue del 77%, sin mortalidad intraoperatoria alguna. La tasa de supervivencia a los 5 años en 5 pacientes con nódulos metastásicos y 8 sin resección biliar extrahepática fue del 80% y 100%. Una segunda operación más radical en 8 pacientes proportionó una tasa de supervivencia a los 5 años del 75%. Un factor pronóstico determinante fue la invasión perineural que se asociaba a la extensión del tumor hacia el cuello o al conducto cístico. La hepatectomía parcial generalmente acompañada de resección de la vía biliar extrahepática y linfadenectomía regional parece constituir la técnica quirúrgica estándar para los carcinomas pT2 de vesícula biliar, pero en los cánceres limitados al fundus y cuerpo de la vesícula se puede respetar la vía biliar extrahepática. Una segunda operación más radical, aumenta la posibilidad de curación en pacientes con carcinomas pT2 de vesícula biliar.

Aggressive repeat liver resection for hepatic metastases of colorectal carcinoma.

Although hepatectomy for liver metastases from colorectal carcinoma is an effective treatment, recurrence in the liver is still the most common site after hepatectomy. Thirty patients underwent hepatectomy for hepatic metastases and 17 of them had recurrence in the remnant liver during the following 12-year period. Six of the 17 patients underwent a removal of isolated hepatic recurrences. Two of the six patients underwent a third hepatectomy, and three patients underwent partial lung resection on a total of five occasions. There were no operative deaths while complications after a third hepatectomy contributed to a high morbidity rate of 40 per cent. The mean length of survival of the six patients was 28.5 months from the second hepatectomy. The prognosis of the six patients who underwent a repeat hepatectomy was significantly better than that of patients with unresectable recurrence after an initial hepatectomy (p<0.01). The overall 5-year survival of 29 patients excluding one inhospital death was 44.7 per cent. Our results reveal that aggressive removal of isolated and resectable recurrent disease has the potential to improve the prognosis of selected patients with metastatic cancer.

Portal vein thrombosis after splenectomy successfully treated by an enormous dosage of fibrinolytic agent in a short period : report of two cases

Portal vein thrombosis (PVT) after splenectomy in a patient with portal hypertension occurs with unusually high frequency. Recently, two patients with PVT following splenectomy were treated by fibrinolytic therapy with an enormous dosage of urokinase (UK) in a short period. PVT was quickly dissolved without side effects and the patients are now doing well without any recurrence of PVT. Therefore, when there is no evidence of bowel infarction, fibrinolytic therapy with an enormous dosage of UK over a short period is deemed to be both effective and essential as a conservative therapy for PVT.

A 5-year survivor after resection of peritoneal metastases from pedunculated-type hepatocellular carcinoma.

We report herein a 5-year survivor after the resection of peritoneal metastases from pedunculated hepatocellular carcinoma (HCC). A 42-year-old man underwent lateral segmentectomy of the liver, with a diagnosis of pedunculated HCC, on October 10, 1994. The lesion was associated with intratumoral hemorrhage and was covered by the greater omentum, but there were no peritoneal metastases. The patient was readmitted to our hospital 4 months later with right upper quadrant pain. His serum alpha-fetoprotein level was 3ng/dl. Hepatitis B virus surface antigen (HBsAg) and hepatitis C virus antibody (HCV-Ab) were both negative. Abdominal computed tomography (CT) revealed two nodular lesions in the right upper abdominal cavity. He was diagnosed with peritoneal metastases from HCC. Because there were no other distant metastases, laparotomy was performed to resect these tumors. We found two other tumors, located in the mesentery of the appendix and ileum. All four tumors were resected by partial transverse colectomy and appendectomy. The histopathology of the tumors showed poorly differentiated HCC (Edmondson-Steiners grade III). The patient has been doing well without recurrent disease for more than 5 years after the second operation. The prognosis of patients with pedunculated HCC is poor. Furthermore, resection for peritoneal metastases from HCC is rare because of the presence of multiple seeding in the abdominal cavity and distant organ metastases. To our knowledge, our patient is the longest survivor after resection of peritoneal metastases from pedunculated HCC.

Clinicopathological features of hepatocellular carcinomas (HCCs) arising in patients without chronic viral infection or alcohol abuse : a retrospective study of patients undergoing hepatic resection

BackgroundThis study was carried out to clarify the etiology and clinicopathological features of hepatocellular carcinomas (HCCs) arising in patients without chronic viral infection or alcohol abuse.MethodsHCC patients who underwent resection were divided into three groups: a non-B non-C (NBNC) group (n = 13), who were seronegative for hepatitis B surface antigen (HBs Ag) and anti-hepatitis C antibody (HCV Ab), excluding a history of alcohol abuse; a B group (n = 25), who were seropositive for HBs Ag only; and a C group (n = 116), who were seropositive for HCV Ab only. We analyzed the features of tumor- and host-related factors and the outcome of the NBNC group.ResultsHepatic inflammation and fibrosis were less severe in the NBNC group than in the other groups. There were no significant differences in tumor-related factors, except for higher serum levels of α-fetoprotein in the NBNC group. Recurrence rates and disease-free survivals were comparable among the three groups. The NBNC group comprised a greater population with one or two recurrent hepatic lesions (P < 0.05), and indocyanine green retention rates and fibrosis scores were preserved after the initial hepatectomy. The NBNC group had higher resection rates for intrahepatic recurrences (75.0%) than the other groups (21.1% and 22.2% in groups B and C, respectively; P < 0.05 and P < 0.05). The survival rate after the initial hepatectomy or detection of the recurrent lesions was significantly better in the NBNC group (both 100% at 5 years) than those in groups B and C (P < 0.05).ConclusionsNBNC patients maintained good liver function following the initial hepatectomy, and tended to have one or two recurrent lesions. These biological advantages provided NBNC patients more opportunities for repeat resection of intrahepatic recurrences, which may lead to a favorable outcome.

Hepatic inflammatory pseudotumor mimicking intrahepatic cholangiocarcinoma: report of a case.

Hepatic inflammatory pseudotumor (IPT) is a relatively rare lesion comprised of proliferating fibrovascular tissue infiltrated by inflammatory cells. IPT has a potential for recurrence and persistent local growth. We present a case of hepatic IPT mimicking a periductal-infiltrating type of intrahepatic cholangiocarcinoma (ICC) in a patient whose serum carbohydrate antigen 19-9 was slightly elevated. We performed a left hepatic lobectomy with resection of the extrahepatic bile duct and regional lymph node dissection under a preoperative diagnosis of ICC. However, histlogical examination of the resected tumor revealed granuloma tissue with lymphocyte infiltration, mainly by plasma cells, and proliferation into the surrounding connective tissue, and the lesion was ultimately diagnosed as hepatic IPT. This case points out the difficulties in differentiating between hepatic IPT extending along Glissons sheath and ICC, based on imaging findings alone.

The role of endothelin in the pathophysiology of renal impairment during acute liver rejection.

We assessed the role of endothelin in the development of renal dysfunction during acute rejection by examining the effect of a selective endothelin A (ETA) receptor antagonist BQ-123 in rats with acute liver rejection. Serum endothelin levels and endogenous creatinine clearance (Ccr) were monitored on days 1, 3, 5, 7, and 9 postoperatively. As indicators of renal hemodynamics, the estimated hemoglobin concentration of renal tissue (IHb) and the oxygen saturation of hemoglobin in renal blood (ISO2) were determined by reflectance spectrophotometry. In addition, the clearance of inulin and p-aminohippurate were determined, and the renal tissue blood flow was estimated by laser-Doppler flowmetry (LDF). As a model of allograft rejection, Lewis rats were transplanted orthotopically with DA rat livers. The serum endothelin level of allografted rejectors was significantly (P<0.05) higher than that of isografted controls (Lewis rats with Lewis livers) on postoperative day 5, and it increased to a maximum of 5.38pm0.95 pg/ml on day 9 (versus 1.23pm0.18 pg/ml preoperatively). The values of Ccr, IHb, and ISO2 were all significantly (P<0.05) lower in allografted rejectors than in isografted controls on day 5, and subsequently declined to a minimum on day 9 (P<0.01). Treatment of allografted rejectors with BQ-123 markedly improved the renal parameters to levels similar to those in the isografted controls. These results strongly suggest that endogenous endothelin may play an important role in the development of renal impairment during acute liver rejection by reducing renal blood flow through binding with ETA receptor.

Kupffer cells modulate splenic interleukin-10 production in endotoxin-induced liver injury after partial hepatectomy.

BACKGROUND/AIMS This study was conducted to investigate the implication of Kupffer cells and the spleen in interleukin (IL)-10 production in endotoxin-induced liver injury after hepatectomy. METHODS Rats were divided into five groups: the S group, sham-operation; the SG group, sham-operation followed by intravenous gadolinium chloride (GdCl(3): 7 mg/kg) administration to inhibit Kupffer cell function; the H group, two-thirds hepatectomy; the HG group, hepatectomy and subsequent GdCl(3) administration; the HGS group, hepatectomy and splenectomy with GdCl(3) administration. Lipopolysaccharide (1.5 mg/kg) was intravenously administered for each group 48 h after surgery. RESULTS GdCl(3) treatment significantly suppressed the elevation of plasma tumor necrosis factor (TNF)-alpha levels by lipopolysaccharide administration with completely inhibited induction of hepatic TNF-alpha and IL-10 mRNAs. In the HG group, marked increase in plasma IL-10 levels associated with enhanced splenic IL-10 mRNA was observed 1 h after lipopolysaccharide administration when compared to those in the H and HGS groups. Plasma TNF-alpha/IL-10 ratio 1 h after lipopolysaccharide administration was higher in the order of H, HGS and HG groups. Hepatic parenchymal damage and the 24-h mortality were lowest in group HG, followed by groups HGS and H. CONCLUSIONS Kupffer cells after hepatectomy may aggravate endotoxin-induced liver injury via down-regulation of IL-10 production in the spleen.