Yoshiro Nishiwaki

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.

Gastric Outlet Obstruction Caused by a Heterotopic Pancreas in a Pregnant Woman: Report of a Case

A 26-year-old Japanese woman who was 23 weeks pregnant presented with nausea, vomiting, and abdominal pain. Gastroduodenal endoscopic examination revealed an oval-shaped submucosal tumor obstructing the gastric outlet at the prepyloric area in the stomach. Magnetic resonance imaging showed a 5-cm cystic tumor and we suspected a degenerated gastrointestinal stromal tumor. No other radiological tests were done because of the associated risks to the fetus. Distal gastrectomy was performed and a histological diagnosis of heterotopic pancreas was confirmed. The patient had an uneventful postoperative course and was discharged 19 days after her operation. She delivered a healthy, full-term male infant 3 months later. This case of an ectopic pancreas obstructing the gastric outlet in a pregnant woman is reported and discussed due to its rarity.

Photofrin-PDT for Gastric Cancer in the Era of Endoscopic Submucosal Dissection

Background: Endoscopic mucosal resection (EMR) was originated to treat early gastric cancer (EGC). EMR was suitable for small, mucosal and well-differentiated adenocarcinoma without ulceration. It was difficult to resect larger tumors en bloc by this method. In recent years, a more useful method, endoscopic submuscosal dissection (ESD) has been developed, which enables en bloc resection of large mucosal lesions. On the contrary, photodynamic therapy (PDT) is applicable to submucosal, poorly differentiated, or carcinoma with ulceration. In the era of ESD, we evaluated the value of Photofrin-PDT. Patients & Methods: We applied PDT to 36 patients including three advanced cancers, who had been excluded from EMR (ESD) and were at high risks for surgery or refused surgery. Four EGC patients who had not been cured by EMR (ESD) were included. Our PDT procedure consisted of polyhematoporphyrin ether/ester administration (Photofrin, 2 mg/Kg) and pulsed excimer dye laser irradiation at 630 nm 48 hours (and 96 hours) after sensitization. Results: Complete response (CR) at three months was obtained in 84% (21/25) of mucosal cancer and in 50% (4/8) of submucosal cancer. Although three patients with an advanced cancer improved but were not cured, quality of their life was maintained. There were no serious side effects except skin photosensitivity. Conclusion: Photofrin-PDT should be applied not only EGC patients who are excluded from ESD and have not been cured by ESD with poor risk for surgery, and have high possibilitiy to be cured by PDT, but also advanced cancer patients for local improvement of lesions.

Feasibility and validity of hepatic vein reconstruction in hepatectomy for hepatocellular carcinoma

The majority of hepatocellular carcinomas are complicated by liver cirrhosis. Cirrhotic patients with a tumor located in segments 7 and 8 cannot tolerate right lobectomy. To perform curative resection without causing liver failure in such patients, resection of segments 7 and 8, together with resection of the right hepatic vein, is recommended. Nine patients underwent such resection. In four patients, the right hepatic vein was not reconstructed. One patient died of liver failure and the other two patients had postoperative liver dysfunction. Based on this experience, the right hepatic vein was reconstructed in the remaining five patients; the defect was repaired by transplanting a vein graft in three patients, and a patch graft was carried out in two. In one patient who underwent reconstruction with vein graft, veno-venous bypass was performed between the remnant hepatic vein and inferior vena cava. This procedure decompressed the remnant liver and facilitated secure anastomosis in reconstruction of the hepatic vein. There were no complications or deaths. The reconstructed veins were patent 2–3 years postoperatively. This procedure is feasible and valid, and should be widely practiced in patients with a diminished liver function reserve.

Usefulness of a wavelength tunable optical parametric oscillator laser on photodynamic therapy

By rotating the optical axis of a nonlinear optical crystal ((beta) -BaB2O4), a tunable laser beam could be obtained from an optical parametric oscillator (OPO) laser. When the crystal was optically pumped by the third harmonics of the 1064 nm Nd:YAG laser, we had a coherent beam from 410 nm through 2550 nm continuously without changing the optical cavity. We compared photodynamic therapy (PDT) effects of two photosensitizers, phenophorbide a(Phd) and Photosan-3(Ph-3, hematoporphyrin-polyester), on Wistar rat liver. Twenty-four hours after sensitization (5 mg/kg i.v.), 670 nm and 630 nm light (75 mW/cm2) was irradiated for Phd and Ph-3 respectively at energy doses of 25, 50, and 100 J/cm2. The rats were sacrificed 24 hours after laser irradiation and analyzed pathologically. Phd produced more severe necrosis than Ph-3. Twenty-five J/cm2 of Phd was identical with 100 J/cm2 of Ph-3. Next, we treated HeLa cell tumors of nude mice by Phd 670 nm PDT and Ph-3 630 nm PDT. The PDT effects of the two photosensitizers on HeLa cell tumors were similar to those on normal liver tissue. In conclusion the OPO laser could make it possible to compare PDT effects of photosensitizers by activating them with their matched wavelengths.

Extensive Surgery for Carcinoma Recurrence After Initial Hepatectomy for Liver Metastasis of Colorectal Carcinoma

Since 1978, we have performed extensive resection for recurrent carcinoma after initial hepatectomy for liver metastasis of colorectal carcinoma. Twenty-five patients had recurrence of carcinoma, and 14 of them had a resectable metastatic tumor. Eight patients with hepatic metastases underwent repeat hepatectomy on 11 occasions, and 8 patients, who had lung metastases underwent partial pulmonary resection on 11 occasions. Two patients underwent brain resection on 3 occasions, and one patient underwent right adrenalectomy combined with grafting of a 4.5-cm segment of the inferior vena cava. Results after surgery were compared with those obtained in 11 patients with nonresectable recurrent carcinoma. There were no operative deaths. The 5-year survival rate after initial hepatectomy in patients undergoing repeat hepatectomy, and pulmonary resection was 42.9 % and 37.5 %, respectively. Thus, surgical treatment of recurrence after hepatectomy achieved a significant improvement of survival compared with patients who had nonresectable recurrence (p<0.01).