Kouji Tsugawa

Immunohistochemical localization of vascular endothelial growth factor in the rat portal hypertensive gastropathy

Background and Aims: Portal hypertensive gastropathy (PHG) is now recognized to be a distinct entity. Recently, angiogenesis has been noticed as a key factor in clarifying the pathophysiology of various diseases. Angiogenesis in the PHT of explored gastric mucosa has yet to be explored. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. The aim of the present study was thus to investigate whether the hypoxic state exists in PHG, and whether VEGF appears more strongly in PHG than in normal gastric mucosa and, if so, what exactly is the role of the hypoxic state and VEGF in PHG.

Anatomie resection for severe blunt liver trauma in 100 patients: Significant differences between young and elderly

The liver is the organ most commonly injured during blunt abdominal trauma. As our society ages, emergency surgery for active elderly patients increases, but data on aggressive emergency hepatic resection remain scarce in the literature. The purpose of this study was to determine whether the elderly (70 years of age or older) can tolerate major liver injury and subsequent hepatic resection. We investigated 100 patients who were treated by an anatomic resection for severe blunt liver trauma (29 elderly patients who were 70 years of age or older and 71 young patients who were younger than 70 years of age) in a retrospective study. The elderly patients were more severely injured as demonstrated by a higher Injury Severity Score, a lower Glascow Coma Scale, and lower survival (80.3% vs. 65.5%; p<0.05). The total number of associated injuries was greater in elderly patients. Motor vehicle accidents were responsible for 71.8% of the injuries in the young group, and the predominant mechanism in the elderly patients was also motor vehicle accidents (51.7%). The 71 anatomic hepatic resections performed on the young patients included right hemihepatectomy (n=45), left lateral segment resection (n=14), bisegmentectomy (n=5), and others. The 29 anatomic hepatic resections performed for the elderly patients were right hemihepatectomy (n=15), left lateral segment resection (n=5), left hemihepatectomy (n=4), and others. Pneumonia, subphrenic abscess, and urosepsis occurred at a significantly higher frequency in elderly patients than in young patients. Our data clearly indicated that (1) the mechanism of injury, grade of associated intraabdominal injuries, distribution of surgical procedures, and complications differ significantly between young and elderly patients; and (2) the survival rate (65.5%) in elderly patients may be sufficient to consider anatomic hepatic resection to be a useful, safe procedure.RésuméLe foie est l’organe le plus souvent lésé lors des traumatismes fermés de l’abdomen. En raison du vieillissement de notre société, le besoin d’envisager une chirurgie d’urgence pour les gens âgés augmente. Cependant, les données dans la littérature sur les résections hépatiques agressives en urgence sont très rares. Le but de cette étude a été de déterminer comment le sujet âgé de 70 ans ou plus supporte des lésions hépatiques majeures et ensuite comment il supporte une résection hépatique en conséquence. Nous avons revu rétrospectivement les dossiers de 100 patients traités par résection réglée pour traumatisme fermé sévère du foie (29 patients âgés qui avaient 70 ans ou plus, et 71 patients plus jeunes, moins de 70 ans). Les patients âgés de 70 ans ou plus avaient des lésions plus graves comme on pouvait le constater par un score ISS plus élevé, un score de Glasgow plus bas, et un taux de survie plus bas (80.3 vs. 65.5%, p<0.05). Le nombre total de lésions associées était plus élevé chez les patients plus âgés. Les accidents de voitures étaient responsables de 71.8% des lésions chez les plus jeunes; ils étaient également la cause principale chez les personnes âgées (51.7%). Parmi les 71 résections hépatiques réglées chez le sujet jeune, on note, parmi les interventions principales, l’hémihépatectomie droite (n=45), la résection segmentaire latérale gauche (n=14) et la bisegmentectomie (n=5). Parmi les 29 résections hépatiques réglées chez les sujets plus âgés, on note principalement l’hémi hépatectomie droite (n=15), la résection segmentaire latérale gauche (n=5) et l’hémihépatectomie gauche (n=4). On a noté plus de complications comme l’infection pulmonaire, les abcès sous-phréniques et les infections urinaires chez les patients plus âgés que chez le patient plus jeune. Nos données indiquent clairement que: (1) le mécanisme des lésions, le degré des lésions intra-abdominales associées et les complications diffèrent significativement entre les patients ages et jeunes, et (2) le taux de survie (65.5%) chez les patients plus âgés est une preuve que la résection hépatique réglée chez le sujet est utile et sure.ResumenEl hígado es la víscera que con más frecuencia se lesiona en los traumatismos cerrados de abdomen. Dado que nuestra sociedad envejece más, la cirugía de urgencia en pacientes añosos es cada vez más frecuente. Sin embargo, la bibliografía sobre las resecciones hepáticas urgentes es escasa. El objetivo del trabajo fue averiguar si los viejos (de 70 o más años) pueden o no soportar traumatismos hepáticos mayores, así como la subsiguiente resección hepática. Se estudiaron retrospectivamente 100 pacientes que por grave traumatismo cerrado de hígado requirieron una resección hepática anatómica (29 tenÍan 70 o más años y 71 menos de 70 años). Los pacientes añosos presentaron traumatismos más graves como demostraba su alta puntuación en la escala ISS, la baja puntuación en la GCS y la escasa supervivencia (80.3 vs 65.5%, p<0.05). El número total de traumatismos asociados fue mayor en los pacientes añosos. Los accidentes viarios fueron la causa etiológica más frecuente tanto en los traumatizados jóvenes (71.8%) como en los viejos (51.7%). En pacientes jóvenes se practicaron 71 hepatectomías anatómicas que comprendieron: hemihepatectomía derecha (n=45), resección segmenteria lateral izquierda (n=14), bisegmentectomía (n=5) y otros tipos de resección. En ancianos, se realizaron 29 resecciones hepáticas anatómicas: hemihepatectomía derecha (n=15), resección segmentaria lateral izquierda (n=5), hemihepatectomía izquierda (n=4) y otros tipos de resecciones. Complicaciones tales como pneumonías, abscesos subfrénicos, urosepsis, fueron mucho más frecuentes en los pacientes añosos. Nuestros hallazgos demuestran: (1) que el mecanismo del trauma, el número de lesiones traumáticas asociadas intraabdominales, el tipo de intervención quirúrgica y las complicaciones son totalmente diferentes en pacientes jóvenes que en los viejos y (2) que la supervivencia (65.5%) en los pacientes añosos es alta, por lo que la resección hepática anatómica puede considerarse un procedimiento útil y seguro.

A comparison of an open and laparoscopic appendectomy for patients with liver cirrhosis.

Liver cirrhosis is a critical factor contributing to morbidity and mortality in abdominal surgery, because patients with cirrhosis have a particularly high risk of developing bleeding, infection, and ascites. Laparoscopic appendectomy (LA) recently has gained a lot of attention around the world; however, comparisons between the benefits of LA and those of conventional open appendectomy (OA) for patients with liver cirrhosis have yet to be sufficiently compiled. In the present retrospective study, 40 patients with liver cirrhosis who were diagnosed with acute appendicitis before surgery underwent an appendectomy (OA in 25 patients and LA in 15 patients). This study focused on the operative time, amount of postoperative pain, use of analgesics, the restart of a normal diet, number of complications, length of hospital stay, and cost-effectiveness of the procedure in such patients. The amount of postoperative pain and the length of hospital stay were significantly smaller in the LA group. The mean values of the serum C-reactive protein on postoperative days 1, 3, and 7 were significantly less in the LA group. The number of wound infections and wound bleeding was also less in the LA group. The difference in the total cost of hospitalization was not significant. The cost of the operation was greater in the LA group than in the OA group, whereas the hospitalization cost in the LA group was less than that in the OA group. The results of this study suggest that LA may be superior to OA for the treatment of postoperative pain and postoperative complications for patients with liver cirrhosis. Long-term follow-up studies are still necessary, however, to determine any possible decrease in the number of late complications.

A selective cyclo‐oxygenase‐2 inhibitor, NS‐398, may improve portal hypertension without inducing gastric mucosal injury

Background and Aims: Prostacyclin has been shown to play a role in hyperdynamic circulation in portal hypertension. Recently, a new subtype of cyclo‐oxygenase (COX), COX‐2, which acts as an inducible synthase in response to various stimuli. The aim of this study was to investigate whether COX‐2 contributes to portal hypertension and whether a COX‐2 blockade induces the same sort of gastric mucosal injury as a COX‐1 blockade.

Abnormal PTEN expression in portal hypertensive gastric mucosa: a key to impaired PI 3-kinase/Akt activation and delayed injury healing?

Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is a dual‐specificity phosphatase that has activity toward both phosphorylated peptides and phospholipids. PTEN inhibits activation of Akt, the downstream effector of PI 3‐kinase, which is integral to cell proliferation, migration, survival, and angiogenesis essential for tissue injury healing. PTEN expression and activation during injury healing remain unexplored. Portal hypertensive (PHT) gastric mucosa has impaired injury healing, but the underlying mechanisms remain unknown. We investigated whether impaired healing of injured PHT gastric mucosa is due to abnormal PTEN expression/activation that leads to decreased Akt activation. We also investigated the possible involvement of Egr‐1, which regulates PTEN in some cells (e.g., fetal kidney epithelial cells), and TNF‐α, which can induce Egr‐1 expression. In PHT gastric mucosa 6 h after injury, PTEN protein levels were increased by 2.7‐fold; unphosphorylated PTEN (reflecting activated PTEN) was increased by 2.4‐fold; Akt phosphorylation (reflecting Akt activation) was reduced by 2‐fold; and Egr‐1 expression was increased by 3.3‐fold vs. normal gastric mucosa. TNF‐α neutralization reversed all of the above abnormalities in PHT gastric mucosa, reduced mucosal injury, and enhanced healing. We conclude that, in injured PHT gastric mucosa, overexpressed/activated PTEN leads to the reduced activation of the PI 3‐kinase/Akt pathway that results in impaired injury healing.

Role of endothelin‐1 in congestive gastropathy in portal hypertensive rats

Background : The aim of this study was to determine the role of endothelin (ET)‐1 in portal hypertensive gastropathy (PHG) under portal hypertension, in order to investigate whether the ETA/B receptor inhibitor improves the permeability of gastric mucosal microvessels in PHG.

Role of nitric oxide and endothelin-1 in a portal hypertensive rat model.

Background: Portal hypertension is often accompanied by a hyperdynamic circulation state. Some reports have suggested that nitric oxide (NO) plays an important role in this hyperdynamic state. On the other hand, although endothelin (ET)-1, a powerful vasoconstrictor, was recently identified, little is known about its role in portal hypertension or about the interaction between NO and ET-1. The aim of this study was therefore to investigate whether or not the inhibitor of NO synthase (NOS) might improve portal hypertension, and also to clarify the relationship between NO and ET-1. Methods: Portal hypertensive (PHT) rats, in which hypertension was induced by a two-step ligation of the portal vein (PVL), were used. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), and serum levels of NO and ET-1 were determined in PVL rats treated with two NOS inhibitors with different functions: NG-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). Control (CTR) rats, treated by a sham operation (SO), were also studied. Results: Two-step PVL treatment induced a significant increase in the serum level of NO3- and ET-1 in the portal vein. L-NAME and AG administration significantly decreased PP at doses of 50 mg/kg in PHT rats after 60 min administration, while no inhibitor effected any modification in the CTR rats. Both NOS inhibitors increased MAP and decreased PP and BFV in the portal vein, gastric mucosa, and spleen, in addition to decreasing the serum levels of NO3- and ET-1 in the PHT rats, while neither blockade modified any parameters in the CTR rats. In PHT rats, L-arginine, a NO substance, reversed the effect of L-NAME, while it did not induce any recovery from the AG effect. Conclusions: In PHT rats, NO seems to contribute to portal hypertension. PVL increases not only the serum level of NO3-, but also that of ET-1 in the portal vein. Both L-NAME and AG reduce PP and BFV of the portal vein, spleen, gastric mucosa, and liver. In addition, the inhibition of NOS diminishes the serum level not only of NO, but also of ET-1. Use of an appropriate NOS inhibitor may therefore positively affect the hyperdynamic state in portal hypertension.BACKGROUND Portal hypertension is often accompanied by a hyperdynamic circulation state. Some reports have suggested that nitric oxide (NO) plays an important role in this hyperdynamic state. On the other hand, although endothelin (ET)-1, a powerful vasoconstrictor, was recently identified, little is known about its role in portal hypertension or about the interaction between NO and ET-1. The aim of this study was therefore to investigate whether or not the inhibitor of NO synthase (NOS) might improve portal hypertension, and also to clarify the relationship between NO and ET-1. METHODS Portal hypertensive (PHT) rats, in which hypertension was induced by a two-step ligation of the portal vein (PVL), were used. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), and serum levels of NO and ET-1 were determined in PVL rats treated with two NOS inhibitors with different functions: N(G)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine (AG). Control (CTR) rats. treated by a sham operation (SO), were also studied. RESULTS Two-step PVL treatment induced a significant increase in the serum level of NO3-and ET-1 in the portal vein. L-NAME and AG administration significantly decreased PP at doses of 50 mg/kg in PHT rats after 60 min administration, while no inhibitor effected any modification in the CTBR rats. Both NOS inhibitors increased MAP and decreased PP and BFV in the portal vein, gastric mucosa, and spleen, in addition to decreasing the serum levels of NO3- and ET-1 in the PHT rats, while neither blockade modified any parameters in the CTR rats. In PHT rats, L-arginine, a NO substance, reversed the effect of L-NAME, while it did not induce any recovery from the AG effect. CONCLUSIONS In PHT rats, NO seems to contribute to portal hypertension. PVL increases not only the serum level of NO3-, but also that of ET-1 in the portal vein. Both L-NAME and AG reduce PP and BFV of the portal vein, spleen, gastric mucosa. and liver. In addition, the inhibition of NOS diminishes the serum level not only of NO, but also of ET-1. Use of an appropriate NOS inhibitor may therefore positively affect the hyperdynamic state in portal hypertension.

Role of Vascular Endothelial Growth Factor in Portal Hypertensive Gastropathy

Background and Aims: Portal hypertensive gastropathy (PHG) is now recognized as a distinct entity; however, the angiogenesis in the portal hypertensive gastric mucosa has yet to be elucidated. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. The aim of this study was thus to examine the function of VEGF in the portal hypertensive and non-portal hypertensive gastric mucosa. Method: Forty-five cirrhotic patients were divided into 3 groups as follows. Group I included 15 patients without PHG who were treated with 1.5 g teprenone/day for 8 weeks: PHG(–)-t. Group II included 15 patients with PHG who were not treated with teprenone: PHG(+)-n. Group III included 15 patients with PHG who were treated with teprenone for 8 weeks: PGH(+)-t. The gastric mucosal blood flow (GMBF), the concentration of gastric mucosal VEGF and hexosamine and the endoscopic findings were studied both before and after medication. Results: Before teprenone treatment, the GMBF in the antrum, fundus, fornix were significantly higher in PHG(+)-n than PHG(–)-t. After treatment, the GMBF in the fundus and fornix significantly decreased more than before treatment in the PHG(+)-t. After treatment, the GMBF in the antrum increased significantly more than before treatment in PHG(–)-t. The gastric VEGF and hexoxamine concentration in the antrum were significantly higher in PHG(+)-n than in PHG(–)-t. After treatment, the gastric VEGF and hexosamine concentration in the antrum significantly decreased in PHG(+)-t while no change in concentration was recognized in PHG(+)-n. In the endoscopic findings, a decrease in the PHG score was recognized in 2 patients in PHG(+)-t. Conclusion: Portal hypertensive gastric mucosal change was thus found to trigger a high concentration of VEGF and hexosamine. Such increased activity of VEGF and hexosamine may thus account for the presence of active congestion in PHG.

The effect of carbon dioxide pneumoperitoneum on the portal hemodynamics in a portal-hypertensive rat model.

As use of laparoscopic surgery grows, various complications with pneumoperitoneum have been reported. However, there are no reports on the relation between the carbon dioxide (Co2) pneumoperitoneum and portal hemodynamics. The purpose of this study was to determine how the pneumoperitoneum affects the portal hypertensive state. Portal-hypertensive rats, control rats, and sham operation rats were studied. The mean arterial pressure, portal venous pressure, central venous pressure, red blood flow volume of the viscera, and liver and renal function were investigated. The findings of this study suggest that Co2 pneumoperitoneum at less than 10 mm Hg does not present any undue risk to the portal hemodynamics in portal-hypertensive rats; however, more attention should be paid to the IAP in PHT patients undergoing surgery.

Endoscopic ligation of oesophageal varices compared with injection sclerotherapy in primary biliary cirrhosis.

Background and aims Oesophageal varices are an important complication in primary biliary cirrhosis (PBC). However, there have yet to be any studies made on treatment of oesophageal varices in PBC. We therefore studied the efficacy and related complications of endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) as an initial treatment in primary biliary cirrhotic patients. Methods From December 1985 to March 1999, 29 biliary cirrhotic Japanese patients with portal hypertension and oesophageal varices were treated in our clinics. Eleven patients were treated with EVL and EIS, and 18 patients underwent EIS only. The liver function, renal function and respiratory function were studied before and after endoscopic treatment and any complications were also examined. Results In stages III and IV, significant differences were observed in the serum levels for total bilirubin and &ggr;‐glutamic pyruvic transaminase only in the EIS group. Significant differences were observed in the rate of appearance of pyrexia, retrosternal pain and pleural effusion between the EIS and EVL groups. Conclusion EVL significantly reduced the adverse effects associated with EIS at the initial session in primary biliary cirrhotic patients.