Novel NF1 gene mutation in a Japanese patient with neurofibromatosis type 1 and a gastrointestinal stromal tumor.

Many mutations of the NF1 gene have been reported in patients with neurofibromatosis type 1 (NF1); however, there have been no documented NF1 gene mutations in Japanese NF1 patients. In the present study, we used the polymerase chain reaction (PCR) and DNA sequencing analysis to characterize the NF1 gene in a 53-year-old Japanese patient with NF1 who suffered from neurofibroma, pheochromocytoma, and gastrointestinal stromal tumor (GIST). Direct sequence analyses revealed a single base substitution in the splicing donor site of intron 6 (IVS6 888+1, G --> A) in one NF1 allele, resulting in an altered splice site (ss) in the mutated allele. Splicing at the cryptic 5' ss in the mutated allele generated mRNA with an insertion of 60 nucleotides. In addition, we screened for mutations in exons 9, 11, 13, and 17 of the c-kit gene in GIST and the succinate dehydrogenase subunit D (SDHD) gene in the pheochromocytoma, but we did not detect any somatic mutations. We report here the first case of an NF1 patient with four neoplasms: neurofibroma, pheochromocytoma, astrocytoma and GIST. Our results suggest that the molecular pathogenesis of GISTs in NF1 patients is different from that in non-NF1 patients.

Proximal-type epithelioid sarcoma in a 36-year-old man: closer immunoelectron-microscopic resemblance of the tumor cells to epithelial cells than to mesenchymal cells.

Proximal-type epithelioid sarcoma (PES) is a rare neoplasm. We report a case of PES that arose in the perineal subcutis of a 36-year-old Japanese man who died within 4 months of the first clinical sign, probably due to massive pulmonary metastases. In the present study, we analyzed the tumor obtained at surgery, immunohistochemically, immunoelectron-microscopically and genetically. Although the tumor cells in the patient expressed both cytokeratin and vimentin immunohistochemically, they showed epithelial characteristics immunoelectron-microscopically because they had tonofilaments constructed of cytokeratin, not vimentin. In addition, the cytokeratins expressed on the tumor were glandular-type keratins. These findings indicate that PES may be a form of carcinoma in soft tissue. To ascertain the possible origin of the tumor, we compared the tumor immunohistochemically with fetal tissues. Although notochord and fetal peritoneal mesothelium were similar to the tumor antigenically, we could not confirm the specific origin of the tumor. Furthermore, the p53-WAF1 pathway did not contribute to tumorigenesis in the patient because the tumor had no mutation in exons 5-8 of the p53 gene and was immunohistochemically positive for WAF1.

Microwave coagulation therapy for a liver tumor involving the root of the left hepatic vein of the residual liver after extended right hepatectomy.

A 54-year-old man had received low anterior resection for rectal carcinoma and extended right hepatectomy for a metastatic liver tumor. One year later, imaging studies disclosed a metastatic liver tumor in segment 2 of the liver. The residual left hepatic vein was completely invaded by the tumor from the root of the hepatic vein to the confluence of several branches by intraoperative ultrasonography. To resect partial liver with the involved hepatic vein was deemed impossible. Microwave coagulation therapy was performed on the tumor and the involved hepatic vein, as we had established the safety of microwave irradiation to the main hepatic vein without interference of the hepatic venous flow in an experimental study. The patient remains well 40 months after the surgery without recurrent signs. The hepatic venous flow of the irradiated hepatic vein is maintained well according to serial examination of Doppler ultrasonography.

Is fenestration a safe treatment for adult polycystic liver disease?: A report of refractory complications.

We report a 67-year-old man with highly symptomatic polycystic liver disease. Fenestration was selected to treat symptoms because the cysts were scattered diffusely and the normal liver volume was limited. Although this patient was relieved from symptoms of liver cysts consequently, several severe postoperative complications including disseminated intravascular coagulation, respiratory failure, liver failure, and biliary leakage occurred resulting in a 6-month postoperative hospital stay. Although various treatments for symptomatic adult polycystic liver disease have been advocated, a definitive treatment remains controversial, especially in diffuse adult polycystic liver disease. Fenestration is one of the alternative treatments for the patients whose cysts are difficult to resect. However high morbidity rate should be carefully assessed, if extensive fenestration is needed to treat diffuse adult polycystic liver disease. Further consideration of appropriate treatments for diffuse adult polycystic liver disease is needed.

Tumor thrombus in the splenic vein originated from gastric carcinoma that produced alpha-fetoprotein.

A 72-year-old man was referred with an endoscopic diagnosis of Borrmann 2 type advanced gastric cancer. Further examination revealed tumor thrombus in the splenic vein and high serum level of alpha-fetoprotein without liver disease. Intraoperative ultrasonography revealed that tumor thrombus originated from gastric cancer extended to the splenic vein through the left gastric vein. Total gastrectomy combined with distal pancreatectomy and splenectomy was done to obtain complete resection of cancer and tumor thrombus. Tumor and its thrombus in the splenic vein were diagnosed as a poorly differentiated adenocarcinoma that produced alpha-fetoprotein. We report the case, and discuss about the gastric cancer with portal tumor thrombus and high serum levels of alpha-fetoprotein.

Prediction of pancreatic fistula by amylase levels of drainage fluid on the first day after pancreatectomy.

BACKGROUND/AIMS: We investigated whether it would be useful to monitor amylase levels of drainage fluid after pancreatic surgery for prediction of pancreatic fistula. METHODOLOGY: Twenty-six cases in which amylase levels of drainage fluid were determined after pancreatic surgery, were divided into 14 cases who did not develop pancreatic fistula and 12 cases who developed pancreatic fistula. Changes in amylase levels of sera and urine as well as drainage fluid were monitored. RESULTS: Amylase levels of drainage fluid were significantly higher in cases with pancreatic fistula than in cases without pancreatic fistula on the first postoperative day, but those levels in both groups decreased until the 7th postoperative day without significant difference. However, those levels in cases with pancreatic fistula significantly increased from the 9th postoperative day whereas the levels in cases without pancreatic fistula further decreased. There was no significant difference in amylase levels of sera or urine. CONCLUSIONS: Amylase levels of drainage fluid on the first postoperative day may be useful to predict development of pancreatic fistula and to plan appropriate management.

[Complete remission of esophageal undifferentiated carcinoma with nedaplatin and 5-FU chemotherapy and endoesophageal brachytherapy].

The patient was a 74-year-old female. Type 1 undifferentiated carcinoma (non-small cell type) was detected in the middle of the thoracic esophagus in August 1999. Although the lesion was diagnosed as T2, N0, and Stage II, the patient was judged to be a poor risk, inoperable case because of a complex past history of renal and respiratory dysfunctions, and dysbasia. Intravenous administration of nedaplatin at 15.8 mg/m2 and 5-FU 590.6 mg/m2 were carried out for 5 consecutive days as chemotherapy. The second cycle of chemotherapy was performed with nedaplatin reduced to 11.8 mg/m2 on the basis of the adverse reactions observed after the first cycle, and PR was attained. As for radiotherapy, additional extracorporeal irradiation was judged to be too dangerous from her history, so endoesophageal brachytherapy alone was added, and CR was obtained. The patient has maintained a CR for more than 2 years after discharge. In this poor risk case with a highly malignant undifferentiated carcinoma, an "individualization strategy" was effective.

Hepatocellular carcinoma in a patient with acromegaly and high serum levels of insulin-like growth factor I: report of a case.

A 64-year-old woman with high serum levels of growth hormone, insulin-like growth factor-I (IGF-I), and alpha-fetoprotein resulting from partially treated acromegaly was found to have a tumor under the left diaphragm. The patient also had a history of type C viral hepatitis. Laparotomy revealed that the tumor was fixed to the diaphragm and connected to the liver and spleen. The tumor was excised with partial resection of the diaphragm, liver, and spleen, and a diagnosis of left-sided pedunculated hepatocellular carcinoma (HCC) was made. Further examination showed a higher level of IGF-I receptor mRNA in the tumor than in the normal liver parenchyma. We believe it is likely that the high serum levels of IGF-I may have played a role in the development of the pedunculated HCC in this patient.

[Assessing liver function by magnetic resonance imaging two-dimensional phase-shift flow measurement of portal venous blood flow after oral intake of glucose].

We have already reported that the ratio of portal venous flow 30 min after oral intake of glucose 75 g to that before intake (PVFR30), measured using pulsed-Doppler ultrasonography (US), correlated significantly with other indicators of liver function and that it could be used to estimate hepatic function before surgery, including liver resection. In this study, to assess the disadvantages of pulsed-Doppler ultrasonography, PVFR30 was measured using two-dimensional (2D) phase-shift (PS) magnetic resonance imaging (MRI). PVFR30 was measured in 17 patients and 7 volunteers: 13 with liver cirrhosis (LC) and 11 without LC (non-LC). Portal venous flow could be measured in all patients without any disturbance of intestinal gas or patient fat, or the high degree of technical skill that Doppler US requires. PVFR30 was significantly lower in the LC group than in the non-LC group. In addition, it correlated significantly with other indicators of liver function, including the indocyanine green clearance test, prothrombin time, hepaplastin test, and cholinesterase activity. These results suggest that PVFR30 measured by 2D PS MRI can be used to estimate liver function, and that this MRI method can be performed more easily than pulsed-Doppler US.