Yoshihiko Kubo

Role of infrainguinal bypass in Buerger's disease: An eighteen-year experience

OBJECTIVES The role of bypass to the distal arteries for patients with Buergers disease (thromboangiitis or TAO) remains controversial because of the high incidence of graft failure. We retrospectively reviewed the results of 71 bypasses to evaluate their efficacy. MATERIALS AND METHODS We performed 71 autogenous vein bypasses in 61 patients with TAO. Of the patients, 97% were heavy smokers. The indications for surgery were claudication in 41%, and ischaemic ulcer or gangrene in 59%. Of the bypasses 85% were to the crural arteries or to the arteries below the ankle. The grafts used were 53 single saphenous veins, and 18 venovenous composite grafts. RESULTS There were 38 graft failures, the main causes including anastomosis to a diseased artery, disease progression (which occurred in smokers after surgery), and vein graft stenosis. Of 38, 10 were restored to patency by revision surgery. Primary and secondary patency rates were 48.8% and 62.5% at 5 years, and 43.0% and 56.3% at 10 years, respectively. The patency rates of the postoperative non-smoking group was significantly higher than that of the smoking group (66.8% vs. 34.7%, p < 0.05). Thirty-six patients (59%) had successful revascularisation and returned to full-time work. However, of 28 with secondary failure, 11 underwent amputation, while 14 had persistent disabling claudication. CONCLUSION Bypass to the distal arteries is an effective treatment for TAO patients, and the long-term patency is quite satisfactory as long as patients stop smoking.

Exogenous lysophosphatidylcholine increases non-selective cation current in guinea-pig ventricular myocytes.

Whole cell, patch-clamp studies were performed to examine the effect of lysophosphatidylcholine (LPC) on the membrane current in guinea-pig ventricular myocytes. The addition of 10 μM LPC to the external solution induced a membrane current which had a reversal potential of 0 mV. When Na+, the main cation in the external solution, was replaced by either K+, N-methyl-D-glucamine (NMG) or 90 mM Ca2+, LPC induced a current with the reversal potential near 0 mV, indicating that the current passed through a Ca2+-permeable non-selective cation channel. The order of the cationic permeability calculated from the reversal potential of the current was Cs+ > K+ > NMG > Na+ > Ca2+. Cl- did not pass through the LPC-induced channel. The LPC-induced current was not blocked by Gd3+ in the external solution, nor by the absence of Ca2+ in the pipette solution. In conclusion, LPC induces a Ca2+-permeable non-selective cation channel in guinea-pig ventricular myocytes.

The tumour-localizing properties of porphyrin derivatives

The tumour-localizing abilities of various kinds of porphyrin derivatives in tumour-bearing hamsters were assessed by nitrogen-pulsed laser spectrofluorometry (N2-PLS). On examination of porphine derivatives (from haemoglobin), it was found that the dimer and acetylated and amidated compounds had a high affinity for tumour tissue; the dimer and hydroxylated compound of phorbine derivatives (from chlorophyll) also showed a high affinity. Furthermore, of the metalloporphines (gallium, zinc and indium complexes), those which contained hydrophilic groups showed a high affinity for tumour tissue; of the metallophorbines (gallium, zinc and indium complexes), those which contained hydrophobic groups showed a high affinity. A correlation was found between the side-chain structure of the porphyrins and metalloporphyrins and their affinity for tumour tissue.

Revascularization of canine cryopreserved tracheal allografts

BACKGROUND We examined the blood supply of a cryopreserved tracheal allograft and its morphohistologic changes after transplantation. METHODS In each of 22 dogs, a five-ring tracheal segment was replaced by one of the following tracheal grafts: fresh autografts (n = 8), cryopreserved tracheal allografts (n = 8), or fresh allografts (n = 6). The cryopreserved tracheal allografts were preserved at -196 degrees C for 60 days. No immunosuppressant was given to any of the animals. All grafts were retrieved at 1 and 12 weeks and assessed by microangiography and histology. RESULTS The epithelial denudation and the revascularization of the transverse intercartilaginous arteries were recognized within 7 days as common to each of the three types of grafts. In the cryopreserved tracheal allografts, neither cartilage degradation nor graft shrinkage occurred at 7 days. However, the recanalized transverse intercartilaginous arteries completely disappeared at 12 weeks, and marked shrinkage occurred; the cartilage cells were accompanied by karyolysis and were significantly decreased in number (p < 0.05). Recanalization of the transverse intercartilaginous arteries was also demonstrated in the fresh allografts; however, necrosis abruptly occurred as a result of acute rejection responses. CONCLUSIONS Cryopreservation of a tracheal allograft provided sufficient reduction of the acute rejection responses, and blood supply to the cryopreserved tracheal allograft was established through the recanalized transverse intercartilaginous arteries within 7 days; however, subsequent chronic rejection responses resulted in occlusion of the transverse intercartilaginous arteries and atrophy.

Treatment of experimental tumors with a combination of a pulsing magnetic field and an antitumor drug

We investigated the effects of a combination treatment involving a pulsing magnetic field (PMF) and an antitumor drug, mitomycin C (MMC), on two experimental tumors (fibrosarcoma KMT‐17 and hepatocellular carcinoma KDH‐8) in WKA rats, paying attention to possible potentiation of the therapeutic effect of the antitumor drug. PMF was obtained using a system generating a pulsed current in a solenoid coil. On day 7 after tumor implantation into the right thighs of rats, the region of the tumor was exposed to PMF (frequency 200 Hz, mean magnetic flux density 40 gauss) for 1 h immediately after iv injection of MMC at a dose of 1 mg/kg. Survival rates at day 90 of KMT‐17 implanted rats were 0% (0/10) in the non‐treated group, 34% (4/12) in the MMC‐treated group, 47% (6/13) in the PMF‐treated group and 77% (10/13) in the MMC/PMF combination group. The increase of life span (ILS) of KDH‐8‐implanted rats in the combination therapy group was significantly prolonged (%ILS 17.6%) compared with that in the MMC‐treated (%ILS 3.4%) and PMF‐treated (%ILS 7.6%) groups. By using cultured cells of the above two lines of tumor, the therapeutic effects of MMC and PMF were also determined from the cell colony‐forming efficiency in soft agar. The colony‐forming efficiencies of both cell lines were significantly suppressed in the combination therapy group compared with those in the other single therapy groups. The present results indicate that PMF exhibited a potentiation of the antitumor effect of mitomycin C.

Anastomotic complications after bronchoplastic procedures for nonsmall cell lung cancer

BACKGROUND Anastomotic complications associated with bronchoplastic procedures cannot be completely avoided despite the improvements made in surgical techniques and suture materials. Thus, the present study attempted to clearly define the significant factors influencing anastomotic complications. METHODS Between 1978 and 1998, 47 patients with primary nonsmall cell lung cancer underwent bronchoplastic procedures. The incidences of anastomotic complications were calculated according to each of the following clinical factors: primary site, age, pathologic type, pT factor, pN factor, pulmonary arterioplasty, surgical procedure, suture material, coverage of the anastomotic line, positive resection margin, and preoperative chemotherapy. The results were analyzed using univariate and multiple logistic regression analysis. RESULTS Anastomotic complications occurred in 8 patients. Four had anastomotic dehiscence and 4 had stenosis. Of these 8 patients, the resection margin was diagnosed as being positive in 6 patients. Three showed metastasis of the most distal mediastinal lymph node whereas the others had a residual tumor at the bronchial resection margin. According to multiple logistic regression analysis, only pN factor (p = 0.04) and positive resection margin (p = 0.02) had a significant influence on the complications. CONCLUSIONS Thus, pN2 patients, especially those with metastasis of the most distal mediastinal lymph node and patients with a residual tumor at the bronchial resection margin, have a significantly higher risk of anastomotic complications.

111In-labeled Mn-metalloporphyrin for tumor imaging

We synthesized and developed a new tumor imaging agent, 111In-labeled metalloporphyrin (111In-ATN-10) which consists of a carrier (ATN-10) of the tumor imaging possessing both a non-radioactive manganese complex in the porphyrin ring and a bifunctional chelating group (DTPA) attached to its side chain. The images of the three kinds of tumors were delineated more clearly by 111In-ATN-10 than 67Ga-citrate. Moreover, there was no photosensitivity in ATN-10. 111In-ATN-10 is studied as a new tumor positive scintigraphic agent instead of 67Ga-citrate.

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.

PLANTAR OR DORSALIS PEDIS ARTERY BYPASS IN BUERGER'S DISEASE

The peripheral type of Buergers disease is unresponsive to conservative therapy when accompanied by multisegmental occlusion at the level of the ankle. Between November 1983 and April 1993, we performed 15 bypasses below the ankle for this type of thromboangiitis obliterans in 13 patients (mean age 45.7 years), including four females. Ten patients had intractable toe ulcers with severe pain, and five had foot-threatening ischemia or disabling foot claudication. Eleven patients were heavy smokers, two were passive smokers, and six had a history of sympathectomy. All patients had occlusion of the three main crural arteries or both of the tibial arteries at the ankle. Of the 15 bypasses, 10 were to the medial or lateral plantar arteries, two were to the common plantar artery, and three were to the dorsalis pedis artery. There were three early and three late graft failures. The causes of early graft failure were thrombosis at the site of cross-clamping, anastomosis to a diseased segment, and arterial spasm. The three late failures (>3 months) were due to disease progression in patients who continued to smoke, whereas all grafts remained patent and functioned well in patients who stopped smoking. Because patients with thromboangiitis obliterans are relatively young and active, early healing of ulcers and restoration of normal limb function are important objectives in their treatment. Bypass to the foot arteries can provide an excellent outcome, although special techniques and postoperative cessation of smoking are essential for success.

TUMOR IMAGING WITH [111niIn]MONO-DTPA-ETHYLENEGLYCOL-Ga-DEUTEROPORPHYRIN

Abstract Mono‐DPTA‐ethyleneglycol‐Ga‐deuteroporphyrin (MDEGD) was synthesized, by coordinating non‐radioactive Ga in the porphyrin ring and connecting DTPA (diethylene‐triamine‐N,N,N,N,N,‐pentaacetic acid) to its side chain. By labeling with 111In, chemicals for scintigraphy were developed. They were applied to Syrian golden hamsters with implanted pancreatic gland cancers and C57‐black mice with Lewis lung cancer to enable tumor imaging and biodistribution examination. A comparative study was also conducted with [67Ga]citrate. In the resultant data, [111In]MDEGD showed larger tumor/lung, tumor/kidney and tumor/blood ratio with [67Ga]citrate. The affinity of [nIn]MDEGD in inflammatory tissue was much lower than that of 67Ga citrate. [111In]MDEGD lost its photosensitivity.