Tatsuzo Tanabe

Ectopic thyroid follicles in the submucosa of the duodenum

Ectopic microscopic thyroid follicles were encountered fortuitously in the submucosa of the duodenum in a 63-year-old man undergoing pancreaticoduodenectomy for pancreatic carcinoma. The follicles, filled with a colloid-like substance, were intermingled with Brunners glands of the duodenum. There were no signs or symptoms of a thyroid tumour. The epithelial cells and colloid-like substance were both immunoreactive for thyroglobulin but no cells stained for calcitonin. The possibility of a metastatic origin for the follicles from an occult thyroid carcinoma was excluded by the clinical and histopathological findings. These ectopic thyroid follicles cannot be explained by developmental inclusions or metastasis and may be metaplastic in nature.

HLA-linked susceptibility gene of Takayasu disease

The HLA-A, B, DR and MB antigens were investigated in patients suffering from Takayasu disease (Aortitis syndrome). Out of twenty-one HLA-A and B antigens tested, only HLA-Bw52 was significantly deviated (30147, PF = 63.8%, RR = 7.8) from the controls (14/76, PF = 18.4%). Since in the Japanese, HLA-Bw52 is in positive linkage disequilibria with HLA-DR2 and MB1, the association of the DR2 and MB1 antigens with Takayasu disease was studied. The HLA-DR2 antigen was significantly increased (23/30, PF = 76.7%,, RR = 6.0) in patients compared with the control (18/51, PF = 35.3%). Moreover, an almost perfect association of MBI (29/30, PF = 96.7%, RR = 12.6) with Takayasu disease was demonstrated. This finding supports the hypothesis that the genes in the HLA-D region play a major role in determining the susceptibility to Takayasu disease.

Surgical Treatment of Aneurysms of the Sinus of Valsalva

From 1962 to 1976, 15 patients with aneurysms of the sinus of Valsalva underwent operative correction. All patients survived operation. Follow-up has been carried out for as long as fifteen years (median, six years) after operation. There have been no late deaths and no recurrences. Aortic insufficiency, present in 2 patients before and in 2 after operation, remained well compensated and required no further aortic valve procedure. A double approach, that is, through both the aorta and the involved cardiac chamber, is recommended for sufficient correction.

Development of a Ceramic Heart Valve

A durable and thromboresistant ceramic heart valve comprised of a single crystal alumina disk and titanium nitride (TiN) valve ring has been developed. Blood compatiblity was examined by scanning electron microscopy (SEM) examinations of the valves implanted in sheep for 35 (#1), 26 (#2), 20 (#3), 23 (#4), and 26 (#5) days. The single crystal alumina and TiN surfaces were free of platelet aggregation or fibrin networks, except for some depositions of fibrin and platelets on the outflow TiN ring in #3, and isolated red cells on the outflow TiN ring in #5. Durability testing under high pressure (1750 mmHg = 233 KPa) pulsatile conditions showed that the safety factor of the ceramic valve was more than seven times greater than anticipated. The ceramic valve is promising as an artificial heart valve.

Functional evaluation of tumor‐infiltrating mononuclear cells. Detection of endogenous interferon‐γ and tumor necrosis factor‐α in human colorectal adenocarcinomas

Quantitative evaluation of the levels of interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) in the extracts of tumors and their corresponding normal tissues resected from 43 patients with colorectal adenocarcinoma was done using solid‐phase, sandwich radioimmunoassay. The levels of both IFN‐γ and TNF‐α detected in the tumor tissues were higher than those in the corresponding normal colorectal tissues obtained from each patient. A significant negative correlation was observed between the level of IFN‐γ and TNF‐α in each tumor extract. The decrease of the level of IFN‐γ in the tumor correlated with the advance of clinical stage, and the levels of IFN‐γ of the patients with distant metastases were significantly lower than those of the patients without distant metastases. However, an increase in the level of TNF‐α correlated not only with an enlarged diameter but also with the extent of the primary tumor. Immunohistochemical staining of IFN‐γ and TNF‐α producing cells in tumor tissues showed that IFN‐γ was mainly produced by CD4 + CD8– T‐lymphocytes and TNF‐α was mainly produced by CD11c+ cells with macrophage‐like morphology. These results suggest that CD4+ T‐lymphocytes that produce IFN‐γ might play an important role in the antitumor response against cancer progression in human colorectal adenocarcinomas.

Cytokine regulation of cell-to-cell interactions in lymphokine-activated killer cell cytotoxicity in vitro.

The permanent pancreas carcinoma cell line, PCI-24, was developed in order to analyse cytokine regulation on pancreas carcinoma and lymphokine-activated killer (LAK) cell interaction. PCI cells expressed ICAM-1 and HLA-ABC, but not HLA-DR antigens. PCI cells showed augmented ICAM-1 and HLA-ABC expression when incubated with interferon γ (IFNγ) and tumour necrosis factor α. A similar but weak augmentary effect on the HLA-ABC and ICAM-1 surface expression was seen with interleukin-1β treatment. Natural attachment of LAK to PCI cells was augmented by recombinant IFNγ in close association with ICAM-1 up-regulation on PCI cells. In addition, natural attachment was significantly inhibited by anti-LFA-1 and anti-ICAM-1 antibody treatments. Cytotoxicity of the LAK cells against PCI cells was also significantly inhibited with the same treatment. Thus, the attachment of LAK cells to PCI cells through LFA-1/ICAM-1 molecules appeared to be essential for the cytotoxicity for PCI cells. Pretreatment of PCI cells, but not of LAK cells, with IFNγ or other cytokines resulted in a decrease of susceptibility for LAK cell cytotoxicity. The decreased susceptibility inversely correlated with HLA-ABC expression on the PCI cells. The collective evidence indicates that, although LAK cell attachment to pancreas carcinoma cells through the LFA-1/ICAM-1 molecule is augmented by IFNγ, IFNγ treatment of pancreas carcinoma cells reduces LAK cell cytotoxicity possibly through an increase in HLA-ABC or a regulation of molecules closely associated to HLA-ABC expression.

Wall reinforcement with highly porous Dacron mesh in aortic surgery.

Wall reinforcement with highly porous synthetic Dacron mesh was devised and evaluated in various aortic operations. Excellent attachment of the mesh to the aortic wall, good preservation of pliability of the aorta, and efficient pressure resistance with minimal scar tissue formation were the usual findings. This type of wall reinforcement was employed in 60 patients for the following indications: 1) prevention of suture line complications; 2) wall reinforcement of aortic aneurysm without resection; 3) reinforcement of adventitia or autogenous vein following thromboendarterectomy. It is concluded that reinforcement with highly porous synthetic Dacron mesh should be superior to reinforcement with conventional prosthetic Dacron graft.

New Approach to Aortic Dissection: Development of an Insertable Aortic Prosthesis

We have developed a new aortic prosthesis with which we can replace or reinforce the aorta using a simple percutaneous technique. We have named the new prosthesis the shape-memory aortic prosthesis (SAP); it consists of a spiral-shaped nitinol stent and polyurethane tube. It can be compressed inside a 14F catheter at a low temperature and regain its original shape at above 30 degrees C. As a preliminary study, SAP sutureless grafting into the descending aorta was performed on 10 mongrel dogs. We found that when the proper diameter of SAP was applied, it functioned satisfactorily for 3 months or more. A percutaneous placement technique pertinent to the SAP also was developed and tried on 4 animals. Our procedure was applied to Stanford type B dissection models to close the entry point successfully. This newly developed SAP has potential to be applied to emergency cases of human aortic dissections.

Congenital arteriovenous malformation of the pancreas with jaundice and a duodenal ulcer: Report of a case

Pancreatic arteriovenous malformation (AVM) is a rare condition which may be associated with AVM of other organs or pathological vascular changes. Portal hypertension, which is very difficult to treat, may complicate such cases and thus, the lesion should be resected as early as possible. We report herein the case of a patient with congenital AVM, presenting with jaundice and a duodenal ulcer, in whom pancreatoduodenectomy provided a means of definitive management. To our knowledge, this is the first case of pancreatic AVM to present with jaundice as the initial symptom.

Postoperative adjuvant immunochemotherapy with mitomycin C, tegafur, PSK and/or OK-432 for gastric cancer, with special reference to the change in stimulation index after gastrectomy

In order to evaluate the efficacy of combined immunochemotherapy with mitomycin-C, tegafur, PSK and/or OK-432 as an adjunct for curatively resected gastric cancer, a prospective randomized controlled study using the envelope method was performed, in which 266 institutions from around Japan participated. The 3 year survival rates for all cases, and for ps(+)·n(+) cases, were insignificantly higher in the immunochemotherapy groups receiving PSK and/or OK-432 than in the control group. However, because 28.2 per cent of the cases were excluded from the final statistical analyses, the results of this study may have questionable statistical credibility. Changes in the stimulation index (SI) suggest that the administration of PSK may result in an inhibition of the immunosuppressive activity of cancer patients. The high SI group showed a significantly higher 4 year survival rate than the low SI group.