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Biomedical subjects

T Kosuge

Publications and source records attributed to T Kosuge.

At least 19 recordsLinked to original sources

Postresection recurrence of hepatocellular carcinoma treated by arterial embolization: analysis of prognostic factors.

Of 270 consecutive patients with hepatocellular carcinoma who underwent surgery, 50 who had recurrence and were subsequently treated with transcatheter arterial embolization were analyzed. The longest interval between surgery and recurrence in the 50 patients who underwent transcatheter arterial embolization was 7 yr. Recurrence was initially found in the remnant liver in all patients but one; extrahepatic metastases were detected in 13 patients (26%) during follow-up. A "multiple" type was the most common (64%) hepatic recurrence pattern on angiography, followed by the "solitary" (16%) and "tumor thrombus" (12%) patterns. Hepatic recurrence was most frequently found in the ipsilateral lobe (48%) relative to the site of the primary hepatocellular carcinoma. Multivariate analysis of the factors affecting survival after transcatheter arterial embolization indicated that recurrence pattern (p = 0.025) and distant metastases (p = 0.011) were significant. Of 13 patients with distant metastases, 11 had the "multiple" pattern of hepatic recurrence. Survival rates for all 50 patients after initial surgery and after transcatheter arterial embolization were 90% and 64%, respectively, at 1 yr; 52% and 24%, respectively, at 3 yr; and 27% and 5%, respectively, at 5 yr. On analysis of survival rates after transcatheter arterial embolization in 37 patients with recurrence only in the liver and of the response of recurrent hepatocellular carcinoma to transcatheter arterial embolization, a significant difference was noted between those with "partial response" and "progressive disease" (p less than 0.05) and between those with "no change" and "progressive disease" (p less than 0.05).

Adult

Morphology and pathological significance of focal acinar cell dysplasia of the human pancreas.

Focal acinar cell dysplasia (FACD) was studied in 138 autopsied pancreases by multiple transsection examination and was found in 13 of the pancreases (9.4%). The average number of FACD per pancreas identified in our study was 5.7, ranging from 1 to 20, and the total number was 60. The location of FACD was 22 in head, 18 in body, and 20 in tail of the pancreas. FACD were rare lesions and found in only 41 of 2,819 slides (1.5%). The incidence of FACD seemed to be higher among males than among females, among patients with cancer in other sites than among those with no cancer, among diabetics than among nondiabetics, among heavy smokers than among nonsmokers, and among alcohol abusers than among abstainers. The males and heavy smokers had significantly more nodules of FACD per pancreas than females and nonsmokers. Simple and atypical hyperplasia of pancreatic ducts were found in 119 (86.2%) and 18 (13.0%), respectively. All pancreases with FACD had simple ductal hyperplasia. FACD and atypical ductal hyperplasia coexisted in one patient who had a history of heavy smoking, and this patient had the most nodules of FACD per pancreas among patients with FACD. No FACD was observed in pancreases without ductal hyperplasia. These findings suggested heavy cigarette smoking was one of the possible causes of FACD and ductal hyperplasia of pancreas.

Adolescent

Benign tumors of the liver resected because of a diagnosis of malignancy.

Thirty-two benign hepatic lesions, which were resected because of a diagnosis of malignancy, were reviewed to demonstrate the characteristics of the problem and to consider the best course of management. The preoperative diagnoses included 21 hepatocellular carcinomas, six metastases and five others. As the final diagnosis, hemangioma and focal nodular hyperplasia were the two major lesions mimicking malignancy, accounting for seven and six patients, respectively. Four of seven hemangiomas were atypical, with a considerable amount of fibrosis. Focal nodular hyperplasia and adenoma were misdiagnosed as hepatocellular carcinoma among other malignancies. Two instances each of necrotic tissue and hemangioma were diagnosed as metastatic carcinoma. The lesions that were studied had main features, including a diameter of less than 4 centimeters in 23 patients, evident discrepancy among the roentgenologic diagnoses in 25 patients and no rapid increase in size in 28 patients. Four of nine needle biopsies performed gave false-positive results and did not always provide adequate information. It was concluded that 15 of the 32 patients, who satisfied the aforementioned three criteria, could have been observed more carefully. However, in the other 17 patients, surgical intervention was considered justified because of an indication of a higher likelihood of a real malignancy.

Adenoma

Surgical treatment of intrahepatic cholangiocarcinoma: four patients surviving more than five years.

BACKGROUND: To find the rational surgical strategy for the treatment of intrahepatic cholangiocarcinoma (ICC), clinical features of ICC were studied in 20 patients who underwent hepatic resection in the National Cancer Center Hospital from 1980 to 1990. METHODS: According to the morphologic pattern, we classified the ICCs into two subcategories, mass-forming and infiltrating, which correlated with their biologic behavior. RESULTS: Of 10 patients who underwent hepatectomy for mass-forming ICC, three survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 59.3%, 44.4%, and 44.4%, respectively. Of 10 patients who underwent hepatectomy for infiltrating ICC, one survived more than 5 years without recurrence. The 1-, 3-, and 5-year survival rates were 72.0%, 27.0%, and 27.0%, respectively. The pathologic findings and recurrences indicated that the salient feature of the mass-forming type was its tendency for intrahepatic metastasis especially near a main lesion, and of the infiltrating type was the infiltrative spread via Glisson's capsule and hilar lymph nodal metastasis. CONCLUSIONS: An anatomic and extensive liver resection should be performed for mass-forming ICC, whereas a hepatectomy with excision of the extrahepatic bile duct and hilar lymph nodal dissection is recommended for infiltrating ICC.

Adenoma, Bile Duct

An isolated caudate lobectomy by the transhepatic approach for hepatocellular carcinoma in cirrhotic liver.

A new strategy for the treatment of hepatic malignancy located deep in the cirrhotic liver is reported. A 66-year-old man, who had a 3 cm hepatocellular carcinoma in the cranial part of the caudate lobe, underwent an isolated caudate lobectomy. By transecting along the interlobar plane and opening the hepatic hilus anteriorly, we resected almost the entire caudate lobe without loss of the remaining liver parenchyma.

Aged

[Result of surgical resection of hepatocellular carcinoma in possible candidates for nonsurgical treatments].

Result of hepatic resection in 150 patients with hepatocellular carcinoma (HCC) harboring up to three lesions smaller than 3cm in diameter (PEI candidates) and 144 patients with multiple lesions (TAE candidates) was studied. In PEI candidates, associated liver diseases were liver cirrhosis in 108 patients (72%) and chronic hepatitis in 41 (27.3%). Survival rates at 1-, 3- and 5-years were 98.0%, 83.5% and 61.4%, respectively. Prognosis of the patients with a well-differentiated solitary lesion was particularly good. In TAE candidates, 1-, 3- and 5-years survival rates were 98.5%, 57.8% and 33.7%, respectively. Half of the patients were considered to have multicentric disease, and their prognosis was better than that with intrahepatic metastases. Surgical resection is recommended as a primary treatment of HCC when the patients are feasible for surgery even if nonsurgical treatments are possible. Further study is required to establish the proper indication for nonsurgical procedures as a primary treatment of HCC in patients who are candidates of surgery.

Adult

Signet-ring cell carcinoid: a primary hepatic carcinoid tumor with cytoplasmic inclusions comprising of aggregates of keratin.

A case of primary hepatic carcinoid tumor was recently encountered, which was argyrophil and showed positive reactions to serotonin, gastrin and pancreatic peptide in an immunohistochemical hormonal study. The tumor had unusual morphologic features. The neoplastic cells had a signet-ring cell appearance, similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma. Ultrastructural and immunohistochemical studies revealed the formation of the signet-ring cells to have been caused by the presence of cytoplasmic inclusions consisting of cytokeratins. Further investigation, using eight monoclonal antibodies recognizing cytokeratins of different molecular weights, showed the accumulated cytokeratins to be of low and medium molecular weights. The morphologic observations in this unusual case of hepatic carcinoid tumor are described and reported cases with similar features, for which we propose the term "signet-ring cell carcinoid," are reviewed.

Adult

[Maintenance chemotherapy using UFT and FT for gynecological malignant tumors. The Gunma Prefectural Society for Study of Chemotherapy for Gynecological Cancer].

The Gunma Prefectural Society for Study of Chemotherapy for Gynecological Cancer made a comparative study on postoperative supplementary chemotherapy including UFT and FT-E for gynecological malignant tumors. The number of cases registered totaled 182, which was broken down into ovarian cancer 53 cases, uterine cervical cancer 89 cases and endometrial cancer 30 cases. Complete cases among them consisted of ovarian cancer 53 cases, uterine cervical cancer 86 cases and endometrial cancer 27 cases for a total of 166 cases. Ovarian cancer was stratified into the completely and incompletely removed cases, uterine cervical cancer into postoperative non-irradiated and irradiated cases and endometrial cancer into the positive metastasis (+) group and negative metastasis (-) group. Then the UFT administration group and FT-E administration group were compared for postoperative survival. There were control groups for both ovarian and endometrial cancer. UFT administration showed a significant improvement in the survival rate (P < 0.05) compared to the FT-E administration group in the cases of ovarian cancer completely removed and the cases of endometrial cancer irradiated after operation. No significant difference was observed between other groups compared. The incidence of side effects was 20.6% (20/97) in the UFT administration group and 3.6% (2/55) in the FT-E group. Neither group showed any serious side effects.

Adult

[Effectiveness of intraoperative cytological examination of peritoneal washings for patients with pancreatic cancer].

To confirm the effectiveness of cytological examination of peritoneal washings for detecting invisible micro-peritoneal dissemination in patients with pancreatic cancer, results were analyzed with the survival and the background factors of the patients. Cytological examination of peritoneal washings or ascitic fluid at recto-vesical pouch or pouch of Douglas was performed in 37 patients with primary pancreatic cancer. Positive results for cancer cells were obtained in five of 9 patients (55.6%) who received cytological examination of ascitic fluid and in seven of 28 patients (25.0%) who received that of peritoneal washings. Four of 6 patients (66.7%) with visible peritoneal dissemination showed positive results. These 6 patients died of peritoneal dissemination with about 10 months. Eight of 31 patients (25.8%) without visible peritoneal dissemination showed positive results of the cytological examination. Two of the 8 patients received resection of the tumor. Other 6 patients without resection developed clinically evident peritoneal carcinomatosis. A high positive rate (66.7%) of cytological examination of the patients with visible peritoneal dissemination and a high incidence of appearance of peritoneal carcinomatosis in patients with positive cytological results but without visible peritoneal dissemination (75.0%; positive vs 26.1%; negative) indicate a high reliability of the cytological examination to detect invisible micro-peritoneal dissemination.

Ascitic Fluid

Surgical management of biliary cystadenocarcinoma.

Four patients, one woman and three men, with biliary cystadenocarcinoma were surgically treated during a 7-year period. The mean age was 58 years. Symptoms prior to admission were mild, and blood tests including liver function tests, CEA and AFP were for the most part within the normal range. Surgery followed diagnostic work-up including US, ERCP, CT, angiography and MRI. Radical surgery was accomplished in three patients by extended left lobectomy in two and extended right lobectomy in one patient, respectively, in this latter patient preceded by therapeutic embolization of the right portal branch prior to resection, while the fourth patient had a palliative resection. Histological examination revealed papillary adenocarcinoma with mucin production within the cyst. The size of the cyst (maximum diameter) varied between 4.5 and 24 (mean 12) cm. The postoperative course was uneventful in all patients. Two patients are alive with no sign of recurrence 5 and 53 months after surgery, while two patients died after 26 and 75 months, respectively. Thus, radical resection of this rare kind of malignant hepatic tumor seems to offer a chance of long-time survival.

Aged

[Selection of methods for diagnosis and treatment of pancreatic cancer].

The prognosis for ductal cancer of the pancreas is extremely poor. Diagnosis of pancreatic cancer in the earlier stages has become possible by taking note of early symptoms, mild abdominal pain, back pain, anorexia, diabetes and obstructive jaundice. Presently, measurements of amylase in serum and urine, serum elastase-1, serum CA 19-9 and US are usually used for screening patients with the symptoms. Furthermore, for correct diagnosis, intensive study by US, dynamic CT, ERCP, MRI, cytological examination and CEA of pancreatic juice, endoscopic pancreatoscopy and endoscopic ultrasonography are used. The results of surgical treatment for resectable pancreatic cancer are not generally favorable. Extended pancreatic resection (pancreatoduodenectomy, total pancreatectomy or distal pancreatectomy) with en bloc dissection of the lymph nodes has been performed for patients with invasive cancer. However, local recurrence and distant metastasis usually occurred after surgery. It seems difficult to cure pancreatic cancer by surgery alone. To improve the prognosis of resectable pancreatic cancer, multimodality treatment with intraoperative radiation therapy and chemotherapy is performed and a better outcome is achieved.

Antineoplastic Combined Chemotherapy Protocols

Distribution and therapeutic effect of intraarterially transferred tumor-infiltrating lymphocytes in hepatic malignancies. A preliminary report.

Indium-111-labeled tumor-infiltrating lymphocytes (111In-TIL) were transferred as an intrahepatic arterial bolus to determine their in vivo distribution in patients with hepatic malignancies. In the in vitro culture system, TIL were expanded upon simultaneous stimulation by recombinant interleukin-2 (rIL-2) and immobilized anti-CD3 monoclonal antibody. This double activation led not only to a larger cell yield, but also to a significantly more dominant subpopulation with CD4+ phenotype than occurred with activation by rIL-2 alone. Accumulations of 111In-TIL in the liver were identified by scintigraphy in all of three patients, corresponding to the tumor localization by computed tomography. Such accumulation had persisted for at least 48 hours after infusion. After intraarterial chemoimmunotherapy that included TIL, two of three patients achieved a partial therapeutic response. The authors conclude that their method of culture and transfer can facilitate the accumulation of TIL at tumor sites, which may augment the antitumor effects of adoptive immunotherapy.

Adenocarcinoma

Evidence of effective multidisciplinary treatment for resectable pancreatic cancer from the viewpoint of the CA19-9 level.

Nineteen patients with resectable pancreatic cancer have been treated by a multidisciplinary approach at the National Cancer Center Hospital. This therapy included extended pancreatic resection, intraoperative irradiation by 30 Gy of electrons, and intraoperative hepatic arterial or portal infusion of mitomycin C. Furthermore, postoperative chemotherapy with mitomycin C, using Seldinger's method or iv administration, was added. The study consisted of 13 patients with carcinoma of the pancreatic head and six patients with carcinoma of the body and tail. The one- and three-year survival rates for these patients were 88 and 50%, respectively. The five-year survival rate was calculated as 28%, although there is only one five-year survivor. The effectiveness of this therapy was studied by changes in Carbohydrate Antigen 19-9 (CA19-9) level. Thirteen of the 15 patients with high CA19-9 levels showed a decrease to a level less than 50 U/mL after this therapy. In the postoperative course, the patients showing a tendency of elevation of the CA19-9 level could be suspected of having cancer recurrence at this time without any physical sign or other laboratory findings.

Aged

Molecular characterization and expression analysis of the anthranilate synthase gene of Pseudomonas syringae subsp. savastanoi.

The trpE gene, which encodes the large component of the enzyme anthranilate synthase, was isolated from a Pseudomonas syringae subsp. savastanoi (P. savastanoi) cosmid library. Cosmids that complemented an Escherichia coli trpE mutation contained a gene whose product is 86% homologous at the deduced amino acid level to TrpE of Pseudomonas aeruginosa and Pseudomonas putida. Amino acid sequence comparison with other TrpE sequences revealed the existence of conserved regions between the procaryotic and eucaryotic polypeptide sequences analyzed, regions that might be of functional importance. We also report on studies on the expression pattern of this gene. We analyzed the promoter activity of a trpE::lacZ transcriptional fusion, the relative amount of trpE steady-state mRNA, and the activity of anthranilate synthase from cells grown in minimal medium with or without exogenously added tryptophan and in complete medium. We concluded that under the conditions tested, expression of the trpE gene of P. savastanoi is independent of the concentration of tryptophan in the culture medium. Implications of such an expression pattern on the virulence of this bacterium are discussed.

Amino Acid Sequence

Study on the bile salt, sodium scymnol sulfate, from Rhizoprionodon acutus. II. The structures of scymnol, anhydroscymnol and sodium scymnol sulfate.

The crystal structures of anhydroscymnol (I) and scymnol (II), which were prepared from sodium scymnol sulfate (III) isolated from the bile of Rhizoprionodon acutus, have been determined by means of X-ray diffraction analyses. The crystals of I are orthorhombic, space group P2(1)2(1)2(1) with Z = 4; unit-cell dimensions: a = 13.562(2), b = 21.636(2), c = 8.735(2) A; II orthorhombic, space group P2(1)2(1)2, with Z = 4; unit-cell dimensions a = 18.553(2), b = 19.887(2), c = 7.986(2) A. Both structures, (24R,25S)-(+)-24,26-epoxy-5 beta-cholestane-3 alpha,7 alpha,12 alpha,27-tetrol (I) and (24R)-(+)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,26,27-hexol (II), were solved from diffractometric data by direct methods and refined by least-squares calculations to R = 0.073 (I) and R = 0.062 (II) (2044 (I) and 2250 (II) observed independent significant reflections (I greater than 3 sigma(I)), respectively. All the hydroxyl groups of both compounds are involved in a hydrogen-bonding network. The structure of III was determined to be (24R,25S)-(+)-3 alpha,7 alpha,12 alpha,24,26-pentahydroxy-5 beta-cholestan-27-yl sodium sulfate, based on the chemical data that alkaline degradation of III with aqueous potassium hydroxide gives only I.

Bile Acids and Salts

Isolation and structural determination of a mutagenic substance in creatine pyrolysate.

The pyrolysis product of creatine showed potent mutagenic activity to Salmonella typhimurium TA98 with metabolic activation by S9 mix. One of the mutagenic substances in creatine pyrolysate was isolated and named Cre-P-1. Its structure was determined by X-ray crystallography to be 4-amino-1,6-dimethyl-2-methylamino-1H,6H-pyrrolo[3,4-f]benzimidazole- 5,7-dione. Cre-P-1 is the first registered mutagenic heterocyclic amine containing oxygen atoms in the molecule, that has been isolated from pyrolysis products.

Animals

Thickening at the root of the superior mesenteric artery on sonography: evidence of vascular involvement in patients with cancer of the pancreas.

Thickening of the root of the superior mesenteric artery (SMA) was studied by using preoperative sonography in 23 patients with pancreatic cancer and in 10 healthy control subjects. Of the 23 with cancer, 11 had neoplastic involvement of the SMA and 12 did not. Prominent thickening of the area around the SMA with (six patients) or without (five patients) decreased echogenicity compared with the adjacent retropancreatic connective tissue was observed in patients with involvement of the SMA, a finding called the "cuff sign." Mean thickness of the periarterial area in the cancer patients with and without involvement of the SMA and in control subjects were 8.5 mm, 4.0 mm, and 2.9 mm, respectively. With an upper limit of normal of 7.0 mm for the thickness of the SMA, the sensitivity, specificity, and overall accuracy of this sign in the evaluation of involvement of the SMA were 91%, 100%, and 96%, respectively. Decreased echogenicity of the periarterial area was not observed in patients without involvement of the SMA or in control subjects. Our results show that sonographic evidence of periarterial thickening of the root of the SMA (cuff sign), especially with decreased echogenicity, is a reliable finding of tumor infiltration of the SMA in patients with pancreatic carcinoma.

Adult