Kiyotaka Kurachi

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.

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.

Accumulated phosphatidylcholine (16:0/16:1) in human colorectal cancer; possible involvement of LPCAT4

The identification of cancer biomarkers is critical for target‐linked cancer therapy. The overall level of phosphatidylcholine (PC) is elevated in colorectal cancer (CRC). To investigate which species of PC is overexpressed in colorectal cancer, an imaging mass spectrometry was performed using a panel of non‐neoplastic mucosal and CRC tissues. In the present study, we identified a novel biomarker, PC(16:0/16:1), in CRC using imaging mass spectrometry. Specifically, elevated levels of PC(16:0/16:1) expression were observed in the more advanced stage of CRC. Our data further showed that PC(16:0/16:1) was specifically localized in the cancer region when examined using imaging mass spectrometry. Notably, because the ratio of PC(16:0/16:1) to lyso‐PC(16:0) was higher in CRC, we postulated that lyso‐PC acyltransferase (LPCAT) activity is elevated in CRC. In an in vitro analysis, we showed that LPCAT4 is involved in the deregulation of PC(16:0/16:1) in CRC. In an immunohistochemical analysis, LPCAT4 was shown to be overexpressed in CRC. These data indicate the potential usefulness of PC(16:0/16:1) for the clinical diagnosis of CRC and implicate LPCAT4 in the elevated expression of PC(16:0/16:1) in CRC.

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.

Portal Vein Thrombosis Caused by Microwave Coagulation Therapy for Hepatocellular Carcinoma: Report of a Case

Abstract Microwave coagulation therapy (MCT) is one of the treatment modalities for patients with hepatocellular carcinoma (HCC). A 67-year-old man with liver cirrhosis underwent MCT during a laparotomy for a deeply located HCC (2.5 cm in diameter) at the border of the anterior and posterior segments of the right hepatic lobe. Two weeks after MCT, he complained of abdominal fullness. Portal vein thrombosis (PVT) was diagnosed because he had massive ascites and an echogenic mass in the portal vein on abdominal ultrasonography. PVT was successfully treated by fibrinolytic therapy with a selective infusion of urokinase via the superior mesenteric artery (SMA). There have been few reports on PVT as a complication of MCT. Attention should be paid to the possible occurrence of PVT as a critical complication after MCT for liver tumors adjacent to the portal vein. Fibrinolytic therapy via the SMA is thus considered to be an effective approach for PVT after MCT.

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.

Identification and characterization of a novel germline p53 mutation in a patient with glioblastoma and colon cancer.

Germline mutations in the p53 tumor suppressor gene have been identified in patients with Li‐Fraumeni syndrome (LFS) and patients with Li‐Fraumeni‐like syndrome (LFL). However, to date, germline p53 mutations in patients not fulfilling the criteria of LFS or LFL have been reported only very rarely. In our study, a novel germline c.584T>C (p.Ile195Thr) mutation of the p53 gene was found in a 21–year‐old male with a glioblastoma and colon cancer. He had no family history of cancer within second‐degree relatives, and loss of the wild‐type p53 allele and overexpression of p53 protein were observed in both tumors. Functional analyses revealed transactivation and growth suppressive function activities of the Thr195‐type p53 to be impaired. These results suggest germline p53 mutations to possibly be responsible for a subset of young adult patient with multiple malignant tumors, even those not meeting the clinical criteria for LFS or LFL.

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study

EAGLE was a randomized, multicenter phase III study which evaluated the superiority of bevacizumab 10 mg/kg plus FOLFIRI compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC previously treated with first-line bevacizumab plus an oxaliplatin-based regimen. The results suggest that the higher 10 mg/kg dose offers no clear clinical benefit compared with bevacizumab 5 mg/kg in this setting.

The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic ischemia and reperfusion.

BACKGROUND This study was designed to verify the involvement of platelet-activating factor (PAF) in renal damage associated with hepatic ischemia and reperfusion (HIR) injury through the release of endothelin (ET)-1 and to determine the modulating effect of a specific PAF receptor antagonist on these insults in rats. METHODS Male rats pretreated with either normal saline as a vehicle (NS group) or intravenous TCV-309, a PAF receptor antagonist (TCV group), were subjected to 120 min of total hepatic ischemia under an extracorporeal portosystemic shunt. Plasma aspartate transaminase, creatinine, blood urea nitrogen, and ET-1 levels and the relative renal wet weight were determined under nonischemic conditions and at 1, 3, and 6 hr of reperfusion after hepatic ischemia. Changes in mean arterial blood pressure and renal tissue blood flow measurements in the kidney were determined throughout the experiment. RESULTS Increased plasma aspartate transaminase, creatinine, blood urea nitrogen, and ET-1 levels and the relative renal wet weight after HIR in the NS group were significantly suppressed by TCV-309 pretreatment. Mean arterial blood pressure and renal tissue blood flow after HIR in the TCV group were significantly improved when compared with those in the NS group. These effects resulted in attenuation of structural hepatic and renal damage with the improvement of 7-day survival (62%). CONCLUSIONS The present study demonstrates that renal damage as well as critical liver injury is produced after reperfusion following 120 min of total hepatic ischemia. A PAF receptor antagonist may be therapeutically useful to protect against these types of damage via indirect modulation of plasma ET-1 levels.

Two-stage Surgery for Endovascular Repair and Laparoscopic Colectomy for a Patient with Abdominal Aortic Aneurysm and Concomitant Colon Cancer: Report of a Case

Surgical management of abdominal aortic aneurysm (AAA) with concomitant malignancy remains controversial. Commercial availability of a stentgraft may change the treatment strategy for such patients. We present a case of AAA with concomitant colon cancer, in which two-stage surgery consisting of EVAR and subsequent laparoscopic colectomy was performed with an interval of six days. The patients postoperative course was uneventful. For high-risk patients, application of endovascular AAA repair and laparoscopic surgery may decrease the risk of surgical morbidity and mortality.