- Email: [email protected]
TRACHEAL ALLOTRANSPLANTATION IN MAN
433 SERUM AND LIVER TISSUE H.B.V. MARKERS OF
Letters to the Editor
50
CASES OF H.C.C.
IN LOS ANGELES
TRACHEAL ALLOTRANSPLANTATION IN MAN
SiR,—We would like to present a preliminary report of the first allogeneic tracheal transplantation in man. There are several established surgical procedures available for resection and plastic reconstruction of limited tracheal stenoses. Bridging extensive circular defects of the trachea, however, has proved a problem. Denatured implants and those of foreign material have proved unsatisfactory, and most surgeons feel that allogeneic tracheal transplantation is not possible because the allotransplant will usually become necrotic within 2 months. In our experiments we also found that circularly excised and orthotopically reimplanted syngeneic transplants became necrotic within this period. On the other hand, detailed studies in immunologically well-defined individuals showed that tracheal transplants, in contrast to other organ transplants, induce only a weak graft-rejection reaction even in the presence of major histoincompatibility. This may reflect weak organ-specific antigenicity. We concluded that the mechanisms leading to necrosis of tracheal transplants had been misinterpreted as allograft rejection whereas they were more likely to have been ischaemic and infectious in nature. In a series of further experiments we found that tracheas heterotopically implanted into the muscles of the neck remained free of ischsemic and infectious complications. They became revascularised and all tissue components remained intact. This is the background to our attempt at heterotopic/orthotopic tracheal transplantation in man. The recipient was a 21-year-old male with an extensive tracheal stenosis affecting eight segments as a result of reanimation procedures. The donor, also a 21-year-old male, died of severe brain trauma resulting from an accident. HLA typing revealed the following:
were thus one A and two B mismatches. The donor was found for us through Eurotransplant, Leiden. The trachea was removed from the donor while blood circulation persisted. It was suspended during transport -(from Essen to Cologne) in a "Euro Collins" solution at 4°C. The ischxmic time of the resected ten-segment tracheal piece was 160 min. After closure of both oral and aboral lumens of the tracheal segment by mucous flaps from the posterior wall of the transplant it was implanted heterotopically into the sternocleidomastoid muscle of the recipient. It was accepted without complications. 3 weeks later, the transplant was mobilised and
There
orthotopically implanted isoperistaltically, accompanied by
a
vascularised muscular section from the sternocleidomastoid. Tracheostomy or endothetic support was regarded as unnecessarv. The tracheal allograft has become integrated and it has functioned perfectly for 9 weeks without any evidence of rejection, ischoemia, or infection. The patient has been discharged. BB’e believe that combined hetero-orthotopic transplantation of tracheal allografts constitutes a valuable approach to the treatment of extensive defects of the human trachea. E N I.
K.-G. ROSE K. SESTERHENN F. WUSTROW
Clinic,
University of Cologne, D5000 Cologne 41, West Germany
* See text.
chronic infection and hepatocellular carcinoma (H.C.C.) seems to be well established in Africa and Asia where the H.B.v. carrier-rate among the general population and the incidence of H.c.c. are both high. However, this relation has not previously been well established in Europe and North America. Trichopoulos et al. found that of 80 Greek patients with H.c.c., 49% were associated with "active H.B.V. infection" compared with 16 (10%) of the 160 controls. They concluded, by calculation of the relative risk, that the close relation of H.B.V. infection and hepatocellular carcinoma was now established in a European population. We have studied the
H.B.V./H.C.C. correlation in the
U.S.A.13 where the incidence of H.c.c. and the H.B.v. infection rate of the general population are both lower than they are in Greece, but where alcoholic liver disease is much more common than it is in Asia and apparently more common than it is in Greece, thus offering a type of liver disease that must be considered separately if the risk of H.c.c. developing from chronic B-viral disease is to be assessed. Our analysis was restricted to necropsy-proven H.c.c. from the University of Southern California liver unit, in patients from whom there was also stored serum (50 cases). All patients had lived in the Los Angeles area. We tested serum HBsAg, anti-HB, anti-HBs, and liver tissue localisation of HBSAg and
HBcAg. We classified the 50 cases into three groups by thorough histological examinations of non-neoplastic liver tissue, all available clinical information. Group A had (20 cases) underlying non-alcoholic liver disease (10 cases cirrhotic, 10 precirrhotic); group B (22 cases) had underlying alcoholic cirrhosis; and group C (8 cases) had no significant liver disease in non-neoplastic areas of liver. 63 randomly selected patients with alcoholic cirrhosis from whom both sera and post-mortem liver tissue were available formed a control group. Results are given in the table. Continuing H.B.V. infection was considered to be present when at least one of the following was found: serum HBsAg, serum anti-HBc (but negative anti-HBs), tissue HBsAg, or tissue HBAg. The frequency of H.B.V. infection in our series (36%) is not greatly different from that of other studies in the U.S.A.-i.e., 5 of 24 (24%) found by Maupas et al. by anti-HB testing alone in Philadelphia4 and 11 of 27 (41 %) found by Tabor et al. using serum HBsAg and anti-HB testing in Washington, D.C. Thus the frequency of H.B.v. among all patients with H.c.c. in the U.S.A. is smaller than in H.c.c. reported from Africa and Asia. However, subclassification of our H.c.c. patients’ into non-alcoholic chronic liver disease, alcoholic cirrhosis, or normal liver revealed an association between chronic in
conjunction with
HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS MARKERS IN EUROPE AND U.S.A.
SIR,-BX’e read the article by Trichopoulos et al.’ with great The relation between hepatitis B virus (H.B.V.)
interest.
Prichopoulos, D., and others. Lancet, 1978, ii
1217.
2. Peters, R L., Afroudakis, A. P., Tatter, D Am J. clin. Path, 1977, 68, 1. 3. Omata, M., Ashcavai, M., Liew, C. T., Peters, R. L. Gastroenterology, 1979,
76, 279. 4. Maupas, P.,
Werner, B., Larouze, B., Millman, I, London, W. T., O’Connell, A., Blumberg, B. S. Lancet, 1975, ii, 9. 5. Tabor, E., Gerety, R. J., Vogel, C. L., Bayley, A C., Anthony, P P., Chan, C. H., Barker, L. F. J. natn. Cancer Inst. 1977, 58, 1197
Letters to the Editor
50
CASES OF H.C.C.
IN LOS ANGELES
TRACHEAL ALLOTRANSPLANTATION IN MAN
SiR,—We would like to present a preliminary report of the first allogeneic tracheal transplantation in man. There are several established surgical procedures available for resection and plastic reconstruction of limited tracheal stenoses. Bridging extensive circular defects of the trachea, however, has proved a problem. Denatured implants and those of foreign material have proved unsatisfactory, and most surgeons feel that allogeneic tracheal transplantation is not possible because the allotransplant will usually become necrotic within 2 months. In our experiments we also found that circularly excised and orthotopically reimplanted syngeneic transplants became necrotic within this period. On the other hand, detailed studies in immunologically well-defined individuals showed that tracheal transplants, in contrast to other organ transplants, induce only a weak graft-rejection reaction even in the presence of major histoincompatibility. This may reflect weak organ-specific antigenicity. We concluded that the mechanisms leading to necrosis of tracheal transplants had been misinterpreted as allograft rejection whereas they were more likely to have been ischaemic and infectious in nature. In a series of further experiments we found that tracheas heterotopically implanted into the muscles of the neck remained free of ischsemic and infectious complications. They became revascularised and all tissue components remained intact. This is the background to our attempt at heterotopic/orthotopic tracheal transplantation in man. The recipient was a 21-year-old male with an extensive tracheal stenosis affecting eight segments as a result of reanimation procedures. The donor, also a 21-year-old male, died of severe brain trauma resulting from an accident. HLA typing revealed the following:
were thus one A and two B mismatches. The donor was found for us through Eurotransplant, Leiden. The trachea was removed from the donor while blood circulation persisted. It was suspended during transport -(from Essen to Cologne) in a "Euro Collins" solution at 4°C. The ischxmic time of the resected ten-segment tracheal piece was 160 min. After closure of both oral and aboral lumens of the tracheal segment by mucous flaps from the posterior wall of the transplant it was implanted heterotopically into the sternocleidomastoid muscle of the recipient. It was accepted without complications. 3 weeks later, the transplant was mobilised and
There
orthotopically implanted isoperistaltically, accompanied by
a
vascularised muscular section from the sternocleidomastoid. Tracheostomy or endothetic support was regarded as unnecessarv. The tracheal allograft has become integrated and it has functioned perfectly for 9 weeks without any evidence of rejection, ischoemia, or infection. The patient has been discharged. BB’e believe that combined hetero-orthotopic transplantation of tracheal allografts constitutes a valuable approach to the treatment of extensive defects of the human trachea. E N I.
K.-G. ROSE K. SESTERHENN F. WUSTROW
Clinic,
University of Cologne, D5000 Cologne 41, West Germany
* See text.
chronic infection and hepatocellular carcinoma (H.C.C.) seems to be well established in Africa and Asia where the H.B.v. carrier-rate among the general population and the incidence of H.c.c. are both high. However, this relation has not previously been well established in Europe and North America. Trichopoulos et al. found that of 80 Greek patients with H.c.c., 49% were associated with "active H.B.V. infection" compared with 16 (10%) of the 160 controls. They concluded, by calculation of the relative risk, that the close relation of H.B.V. infection and hepatocellular carcinoma was now established in a European population. We have studied the
H.B.V./H.C.C. correlation in the
U.S.A.13 where the incidence of H.c.c. and the H.B.v. infection rate of the general population are both lower than they are in Greece, but where alcoholic liver disease is much more common than it is in Asia and apparently more common than it is in Greece, thus offering a type of liver disease that must be considered separately if the risk of H.c.c. developing from chronic B-viral disease is to be assessed. Our analysis was restricted to necropsy-proven H.c.c. from the University of Southern California liver unit, in patients from whom there was also stored serum (50 cases). All patients had lived in the Los Angeles area. We tested serum HBsAg, anti-HB, anti-HBs, and liver tissue localisation of HBSAg and
HBcAg. We classified the 50 cases into three groups by thorough histological examinations of non-neoplastic liver tissue, all available clinical information. Group A had (20 cases) underlying non-alcoholic liver disease (10 cases cirrhotic, 10 precirrhotic); group B (22 cases) had underlying alcoholic cirrhosis; and group C (8 cases) had no significant liver disease in non-neoplastic areas of liver. 63 randomly selected patients with alcoholic cirrhosis from whom both sera and post-mortem liver tissue were available formed a control group. Results are given in the table. Continuing H.B.V. infection was considered to be present when at least one of the following was found: serum HBsAg, serum anti-HBc (but negative anti-HBs), tissue HBsAg, or tissue HBAg. The frequency of H.B.V. infection in our series (36%) is not greatly different from that of other studies in the U.S.A.-i.e., 5 of 24 (24%) found by Maupas et al. by anti-HB testing alone in Philadelphia4 and 11 of 27 (41 %) found by Tabor et al. using serum HBsAg and anti-HB testing in Washington, D.C. Thus the frequency of H.B.v. among all patients with H.c.c. in the U.S.A. is smaller than in H.c.c. reported from Africa and Asia. However, subclassification of our H.c.c. patients’ into non-alcoholic chronic liver disease, alcoholic cirrhosis, or normal liver revealed an association between chronic in
conjunction with
HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS MARKERS IN EUROPE AND U.S.A.
SIR,-BX’e read the article by Trichopoulos et al.’ with great The relation between hepatitis B virus (H.B.V.)
interest.
Prichopoulos, D., and others. Lancet, 1978, ii
1217.
2. Peters, R L., Afroudakis, A. P., Tatter, D Am J. clin. Path, 1977, 68, 1. 3. Omata, M., Ashcavai, M., Liew, C. T., Peters, R. L. Gastroenterology, 1979,
76, 279. 4. Maupas, P.,
Werner, B., Larouze, B., Millman, I, London, W. T., O’Connell, A., Blumberg, B. S. Lancet, 1975, ii, 9. 5. Tabor, E., Gerety, R. J., Vogel, C. L., Bayley, A C., Anthony, P P., Chan, C. H., Barker, L. F. J. natn. Cancer Inst. 1977, 58, 1197