- Email: [email protected]
Familial papillary carcinoma of the thyroid: a report of nine first-degree relatives of four families
European Journal of Surgical Oncology 2000; 26: 789–791 doi:10.1053/ejso.2000.1005, available online at http://www.idealibrary.com on
Familial papillary carcinoma of the thyroid: a report of nine firstdegree relatives of four families M. Marchesi, M. Biffoni, F. Biancari, C. Faloci, R. Cresti, F. Mariotti, R. Nobili Benedetti and F. P. Campana Division of General Surgery, University ‘La Sapienza’, Rome, Italy
The authors report the occurrence of papillary carcinoma of the thyroid in nine first-degree relatives of four families among a consecutive series of 97 patients with papillary carcinoma of the thyroid who were operated on from 1991 to 1998. Total thyroidectomy was performed in all cases. All patients are alive without evidence of disease after a mean follow-up period of 43 months. Since in our series familial papillary carcinoma of the thyroid was found in 9.3% of patients, we suggest an adequate screening among first-degree relatives of all patients with papillary thyroid carcinoma. Because of reported aggressive behaviour of familial papillary carcinoma of the thyroid, aggressive surgical treatment plus post-operative thyroid remnant ablation with radio-iodine should be warranted in all patients. 2000 Harcourt Publishers Ltd Key words: papillary carcinoma; thyroid; familial; genetics; screening.
Introduction Papillary thyroid carcinoma (PTC) is usually sporadic, but its occurrence has been observed in the members of several families. Epidemiological studies suggested an inheritance subset underlying the occurrence of this tumour.1 HLA B7 and DR1 antigens have been observed more frequently in patients with familial PTC compared with those with sporadic PTC.2 However, the underlying gene responsible for such a disorder and its histopathological phenotype have not been determined. It may occur in association with familial adenomatous polyposis coli, Gardner syndrome, papillary renal neoplasia and the McCune–Albright syndrome.3–6 Differentiated thyroid carcinomas are sometimes also present in Werner syndrome. A poorer outcome of the familial form of PTC compared with sporadic PTC has been reported.7 In this paper, we report the clinical outcome of nine patients with PTC who were first-degree relatives of four families treated in our department during an 8-year period.
dissection was performed in 21 patients and radical neck dissection in one patient. PTC occurred in nine patients (9.3%) who were firstdegree relatives of four families. All the other first-degree relatives underwent screening ultrasound examination of the thyroid, and measurement of serum concentration of thyroid hormones and thyreoglobulin.
Family A In Family A the mother had hypothyroidism, one of her daughters underwent thyroidectomy for a follicular adenoma, another daughter had a goitre associated with hypothyroidism and one son was affected by hypothyroidism. Two other daughters had PTC.
Patients and methods
Case 1. A 28-year-old woman underwent total thyroidectomy plus modified radical neck dissection for a PTC with a diameter of 2.2 cm which invaded the capsule and metastasized to the lymph nodes along the recurrent laryngeal nerves and to the lymph nodes of the anterosuperior mediastinum.
From 1991 to 1998, we have operated on 134 patients with thyroid malignancy, and 97 consecutive patients had PTC and underwent total thyroidectomy. Modified neck
Case 2. Her sister of 33 years of age underwent total thyroidectomy for multinodular goitre and a PTC with a diameter of 0.5 cm.
Family B Correspondence to: Maurizio Marchesi, M.D., Istituto III Clinica Chirurgica, Policlinico ‘Umberto I’, Viale Regina Elena 324, 00161, Rome, Italy. E-mail: [email protected] 0748–7983/00/080789+03 $35.00/0
In Family B parents without evidence of thyroid diseases had three sons and one daughter with thyroid disease. 2000 Harcourt Publishers Ltd
790
M. Marchesi et al.
Case 3. A 31-year-old man underwent total thyroidectomy for multifocal PTCs of the right lobe having a maximal diameter of 3.3 cm. Case 4. His brother of 40 years of age underwent total thyroidectomy for two PTCs involving both thyroid lobes with diameters of 1.6 cm and 1.4 cm, respectively. Case 5. The third brother of 43 years of age underwent total thyroidectomy for multinodular goitre and an encapsulated PTC of 1 cm in size. Their sister underwent total thyroidectomy for euthyroid goitre. Family C Family C consisted of a mother with one son and two daughters, the latter having PTC. Case 6. A 17-year-old girl underwent total thyroidectomy for nodular hyperplasia involving the left lobe and for an encapsulated PTC of the right lobe of 1 cm in size. Case 7. At the age of 24 her sister underwent total thyroidectomy for multifocal PTC with a maximal diameter of 2 cm invading the capsule and thymic tissue. Family D Family D consisted of a mother with a multinodular goitre and two daughters with PTC. Case 8. A 48-year-old woman with hyperthyroidism underwent total thyroidectomy for PTC of 1 cm in size and nodular hyperplasia.
Discussion The incidence of familial PTC has been reported to range from 6.2 to 10.5%,1,8 but these observations are related to even other than first-degree relatives. Our series showed a high incidence of familial PTC in first-degree relatives and it is worth noting that other members of these families were affected by other benign thyroid diseases. The results reported by Lupoli et al.7 suggested a more aggressive behaviour of familial PTC when compared with the sporadic ones. They reported a 1-year mortality rate of 14% and recurrence rate of 43%. Among patients operated on for sporadic PTC, the authors observed a recurrence rate of 4.5%.7 Grossman et al.9 reported a recurrence rate of 50% after 6.5±4.6 years of follow-up, but these results may be due to more advanced stage of the disease in this patient population. Since in the series by Lupoli et al.7 two patients among three cases of recurrent PTC underwent lobectomy and subtotal thyroidectomy, respectively, it is likely that our better results may be due to a more aggressive surgical approach. Our experience suggests that the occurrence of a PTC in a member of a family may stimulate the willingness of his/ her relatives to undergo screening for thyroid malignancies. This may explain why the mean age of patients with sporadic PTC is higher than in patients with familial PTC. Furthermore, our results suggests that early detection among family members may result in a less need for cervical lymphadenectomy than in patients with sporadic PTC (11.1% vs 22.7%, respectively). Note the high incidence of multifocal tumours in our series (44.4%), which is similar to that reported by other authors.2,9 Kraimps et al.1 reported an incidence of multifocal familial PTC of 47%, whereas only 23% of sporadic PTCs were multifocal. An even higher incidence of multifocality (93%) was reported by Grossman et al.,9 with bilateral cancer occurring in 43% of cases.
Case 9. At the age of 37 her sister underwent total thyroidectomy for a multifocal PTC. All patients underwent a total body scan post-operatively with 131I in conditions of marked hypothyroidism (TSH>50 mU/l). Patients with residual thyroid tissue and/or lymphnode metastases received radio-iodine. All patients received suppressive doses of levothyroxine. The mean follow-up period was 43 months (range 12–105 months).
Results The mean age of the overall series of PTC was 43 years, whereas the mean age of patients with familial PTC was 33.4 years. No post-operative death occurred in both groups. Neither permanent nor temporary paralysis of the recurrent laryngeal nerve as well as post-operative hypoparathyroidism occurred among patients with familial PTC. Radio-iodine was given post-operatively in one patient who had metastases to the cervical and mediastinal lymph nodes and in another with a tumour invading the thymic tissue. All patients are alive without evidence of disease after a mean follow-up period of 43 months.
Conclusions The occurrence of familial PTCs in about 10% of cases suggests that an adequate clinical and ultrasound screening for thyroid malignancies should be carried out at least in first-degree relatives of all patients presenting with PTC. This policy may result in early detection of this tumour and there is likely to be a better outcome. Aggressive surgical treatment and, when required, post-operative administration of radioiodine should be warranted in all patients with PTC because of the multifocal nature of the disease and its potential aggressive behaviour.
References 1. Kraimps JL, Bouin-Pineau MH, Amati P, Mothes D, Bonneau D, Marechaud R, Barbier J. Familial papillary carcinoma of the thyroid. Surgery 1997; 121: 715–8. 2. Ozaki O, Ito K, Kobayashi K, Suzuki A, Manabe Y, Hosoda Y. Familial occurrence of differentiated, nonmedullary thyroid carcinoma. World J Surg 1988; 12: 565–71. 3. Kobayashi K, Tanaka Y, Ishiguro S, Mori T, Mitani Y,
Familial papillary carcinoma of the thyroid Shigemasa M. Family with nonmedullary thyroid neoplasms. J Surg Oncol 1995; 58: 274–7. 4. Bulow S, Holm NV, Mellemgaard A. Papillary thyroid carcinoma in Danish patients with familial adenomatous polyposis. Int J Colorectal Dis 1988; 3: 29–31. 5. Plail RO, Bussey HJ, Glazer G, Thomson JP. Adenomatous polyposis: an association with carcinoma of the thyroid. Br J Surg 1987; 74: 377–80. 6. Malchoff CD, Sarfarazi M, Tendler B, Forouhar F, Whalen G, Joshi V, Arnold A, Malchoff DM. Papillary thyroid carcinoma associated with papillary renal neoplasia: genetic linkage analysis of a distinct heritable tumor syndrome. J Clin Endocrinol Metab 2000; 85: 1758–64.
791
7. Lupoli G, Vitale G, Caraglia M, Fittipaldi MR, Abbruzzese A, Tagliaferri P, Bianco AR. Familial papillary thyroid microcarcinoma: a new clinical entity. Lancet 1999; 353: 637–9. 8. Stoffer SS, Van Dyke DL, Vaden Bach J, Szpunar W, Weiss L. Familial papillary carcinoma of the thyroid. Am J Med Genet 1986; 25: 775–82. 9. Grossman RF, Tu SH, Duh QY, Siperstein AE, Novosolov F, Clarck OH. Familial nonmedullary thyroid cancer: an emerging entity that warrants aggressive treatment. Arch Surg 1995; 130: 892–9. Accepted for publication 28 July 2000
Visits to Departments of Surgical Oncology in Europe As part of the educational role of the European Journal of Surgical Oncology, the Editors have decided to introduce a regular section in EJSO designed for departments of surgical oncology throughout Europe to indicate to our readers their encouragement for visits from trainees (both clinical and research). It is generally understood that persons who are willing to visit the centres have arranged their own funding unless otherwise stated. Any of our readers who would wish to visit the centres should contact the institution to plan the visit in more detail. The Department of General Surgery, Institut Gustave-Roussy, Villejuif, France The Institut Gustave-Roussy is located just outside Paris. The Department of General Surgery is a 102-bed unit with 10 full-time and two part-time surgeons, 12 attendants and residents. One psychotherapist works full-time with the team. Three thousand and four hundred operations a year are carried out in six operating theatres. The range of tumours treated are: gynaecological, gastro-intestinal, hepatic, breast, skin, thyroid, urological, bone and soft tissue. There are several outpatient clinics per week. Surgical staff participate at least once a week in multidisciplinary clinical committees. Surgical staff meet once a week to discuss cases and new protocols. Two foreign residents are part of the staff every six months. The Department is an integral part of the most important cancer institute in France with 507 beds and 700 doctors and research workers. The Department of Surgery, University of Heidelberg, Heidelberg, Germany The Department of Surgery at the University of Heidelberg is a 200 bed unit with special clinical section of Surgical Oncology, Vascular Surgery and Trauma Surgery. The Section of Surgical Oncology was instituted in 1982 to provide facilities for rapid translation of new treatment concepts into clinical practice. The section includes a special, wellstaffed 20-bed unit, an outpatient clinic and a unit for oncological documentation. Special treatment facilities include intraoperative radiation therapy in a dedicated operating suite and isolated extremity perfusion. Major clinical activities concern treatment of oesophageal cancer, liver tumours, retroperitoneal malignancies and treatment of tumour recurrence. Clinical protocols currently under evaluation address IORT for soft tissue sarcoma and rectal cancer, adjuvant treatment of colon cancer, adjuvant immunotherapy following curative resection of colorectal liver metastases and chronomodulated neoadjuvant treatment of advanced liver metastases. Visitors are welcome. If they stay for prolonged time periods and have good command of the German or English language, active participation in the section’s scientific activities is encouraged. Contact: T. Lehnert, MD, Section of Surgical Oncology, Department of Surgery, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. Fax: +49-6221-565506; E-Mail: thomas–[email protected] The Department of Surgery and Surgical Oncology, Robert-Ro¨ssle-Hospital, Charite´, Humboldt University, Berlin, Germany The Robert-Ro¨ssle-Hospital is a 200-bed specialized oncology center and is part of the Charite´ Clinic in Berlin. It is located on the campus of the Max-Delbru¨ck-Center for Molecular Medicine, one of the large central biomedical research facilities in Germany. The Department of Surgery and Surgical Oncology is a 68-bed unit including a highly equipped eight-bed intensive care ward. The most frequently treated tumour entities are GI-tract cancers and hepatic malignancies, breast cancer, thyroid cancer, malignant melanoma and bone and soft tissue sarcoma. Active clinical research protocols are based on hyperthermia, isolated limb perfusion with TNF, and photodynamic therapy, as well as innovative staging procedures in cancer. A special research unit (OP 2000) is engaged in all aspects of telemedicine and computer-aided surgery. There is a close cooperation with basic research groups on the campus with projects in tumour invasion and metastasis, multi-drug resistance, hereditary cancer syndromes and gene therapy. Visitors are welcome. Depending upon knowledge, active participation in the clinical and scientific activities is encouraged. Contact: Prof. Dr P. M. Schlag, Robert-Ro¨ssle-Klinik,Lindenberger Weg 80, 13122 Berlin, Germany. Tel: 0049-309417 1400; Fax: 0049-30-9417 1404; E-mail: [email protected]
Familial papillary carcinoma of the thyroid: a report of nine firstdegree relatives of four families M. Marchesi, M. Biffoni, F. Biancari, C. Faloci, R. Cresti, F. Mariotti, R. Nobili Benedetti and F. P. Campana Division of General Surgery, University ‘La Sapienza’, Rome, Italy
The authors report the occurrence of papillary carcinoma of the thyroid in nine first-degree relatives of four families among a consecutive series of 97 patients with papillary carcinoma of the thyroid who were operated on from 1991 to 1998. Total thyroidectomy was performed in all cases. All patients are alive without evidence of disease after a mean follow-up period of 43 months. Since in our series familial papillary carcinoma of the thyroid was found in 9.3% of patients, we suggest an adequate screening among first-degree relatives of all patients with papillary thyroid carcinoma. Because of reported aggressive behaviour of familial papillary carcinoma of the thyroid, aggressive surgical treatment plus post-operative thyroid remnant ablation with radio-iodine should be warranted in all patients. 2000 Harcourt Publishers Ltd Key words: papillary carcinoma; thyroid; familial; genetics; screening.
Introduction Papillary thyroid carcinoma (PTC) is usually sporadic, but its occurrence has been observed in the members of several families. Epidemiological studies suggested an inheritance subset underlying the occurrence of this tumour.1 HLA B7 and DR1 antigens have been observed more frequently in patients with familial PTC compared with those with sporadic PTC.2 However, the underlying gene responsible for such a disorder and its histopathological phenotype have not been determined. It may occur in association with familial adenomatous polyposis coli, Gardner syndrome, papillary renal neoplasia and the McCune–Albright syndrome.3–6 Differentiated thyroid carcinomas are sometimes also present in Werner syndrome. A poorer outcome of the familial form of PTC compared with sporadic PTC has been reported.7 In this paper, we report the clinical outcome of nine patients with PTC who were first-degree relatives of four families treated in our department during an 8-year period.
dissection was performed in 21 patients and radical neck dissection in one patient. PTC occurred in nine patients (9.3%) who were firstdegree relatives of four families. All the other first-degree relatives underwent screening ultrasound examination of the thyroid, and measurement of serum concentration of thyroid hormones and thyreoglobulin.
Family A In Family A the mother had hypothyroidism, one of her daughters underwent thyroidectomy for a follicular adenoma, another daughter had a goitre associated with hypothyroidism and one son was affected by hypothyroidism. Two other daughters had PTC.
Patients and methods
Case 1. A 28-year-old woman underwent total thyroidectomy plus modified radical neck dissection for a PTC with a diameter of 2.2 cm which invaded the capsule and metastasized to the lymph nodes along the recurrent laryngeal nerves and to the lymph nodes of the anterosuperior mediastinum.
From 1991 to 1998, we have operated on 134 patients with thyroid malignancy, and 97 consecutive patients had PTC and underwent total thyroidectomy. Modified neck
Case 2. Her sister of 33 years of age underwent total thyroidectomy for multinodular goitre and a PTC with a diameter of 0.5 cm.
Family B Correspondence to: Maurizio Marchesi, M.D., Istituto III Clinica Chirurgica, Policlinico ‘Umberto I’, Viale Regina Elena 324, 00161, Rome, Italy. E-mail: [email protected] 0748–7983/00/080789+03 $35.00/0
In Family B parents without evidence of thyroid diseases had three sons and one daughter with thyroid disease. 2000 Harcourt Publishers Ltd
790
M. Marchesi et al.
Case 3. A 31-year-old man underwent total thyroidectomy for multifocal PTCs of the right lobe having a maximal diameter of 3.3 cm. Case 4. His brother of 40 years of age underwent total thyroidectomy for two PTCs involving both thyroid lobes with diameters of 1.6 cm and 1.4 cm, respectively. Case 5. The third brother of 43 years of age underwent total thyroidectomy for multinodular goitre and an encapsulated PTC of 1 cm in size. Their sister underwent total thyroidectomy for euthyroid goitre. Family C Family C consisted of a mother with one son and two daughters, the latter having PTC. Case 6. A 17-year-old girl underwent total thyroidectomy for nodular hyperplasia involving the left lobe and for an encapsulated PTC of the right lobe of 1 cm in size. Case 7. At the age of 24 her sister underwent total thyroidectomy for multifocal PTC with a maximal diameter of 2 cm invading the capsule and thymic tissue. Family D Family D consisted of a mother with a multinodular goitre and two daughters with PTC. Case 8. A 48-year-old woman with hyperthyroidism underwent total thyroidectomy for PTC of 1 cm in size and nodular hyperplasia.
Discussion The incidence of familial PTC has been reported to range from 6.2 to 10.5%,1,8 but these observations are related to even other than first-degree relatives. Our series showed a high incidence of familial PTC in first-degree relatives and it is worth noting that other members of these families were affected by other benign thyroid diseases. The results reported by Lupoli et al.7 suggested a more aggressive behaviour of familial PTC when compared with the sporadic ones. They reported a 1-year mortality rate of 14% and recurrence rate of 43%. Among patients operated on for sporadic PTC, the authors observed a recurrence rate of 4.5%.7 Grossman et al.9 reported a recurrence rate of 50% after 6.5±4.6 years of follow-up, but these results may be due to more advanced stage of the disease in this patient population. Since in the series by Lupoli et al.7 two patients among three cases of recurrent PTC underwent lobectomy and subtotal thyroidectomy, respectively, it is likely that our better results may be due to a more aggressive surgical approach. Our experience suggests that the occurrence of a PTC in a member of a family may stimulate the willingness of his/ her relatives to undergo screening for thyroid malignancies. This may explain why the mean age of patients with sporadic PTC is higher than in patients with familial PTC. Furthermore, our results suggests that early detection among family members may result in a less need for cervical lymphadenectomy than in patients with sporadic PTC (11.1% vs 22.7%, respectively). Note the high incidence of multifocal tumours in our series (44.4%), which is similar to that reported by other authors.2,9 Kraimps et al.1 reported an incidence of multifocal familial PTC of 47%, whereas only 23% of sporadic PTCs were multifocal. An even higher incidence of multifocality (93%) was reported by Grossman et al.,9 with bilateral cancer occurring in 43% of cases.
Case 9. At the age of 37 her sister underwent total thyroidectomy for a multifocal PTC. All patients underwent a total body scan post-operatively with 131I in conditions of marked hypothyroidism (TSH>50 mU/l). Patients with residual thyroid tissue and/or lymphnode metastases received radio-iodine. All patients received suppressive doses of levothyroxine. The mean follow-up period was 43 months (range 12–105 months).
Results The mean age of the overall series of PTC was 43 years, whereas the mean age of patients with familial PTC was 33.4 years. No post-operative death occurred in both groups. Neither permanent nor temporary paralysis of the recurrent laryngeal nerve as well as post-operative hypoparathyroidism occurred among patients with familial PTC. Radio-iodine was given post-operatively in one patient who had metastases to the cervical and mediastinal lymph nodes and in another with a tumour invading the thymic tissue. All patients are alive without evidence of disease after a mean follow-up period of 43 months.
Conclusions The occurrence of familial PTCs in about 10% of cases suggests that an adequate clinical and ultrasound screening for thyroid malignancies should be carried out at least in first-degree relatives of all patients presenting with PTC. This policy may result in early detection of this tumour and there is likely to be a better outcome. Aggressive surgical treatment and, when required, post-operative administration of radioiodine should be warranted in all patients with PTC because of the multifocal nature of the disease and its potential aggressive behaviour.
References 1. Kraimps JL, Bouin-Pineau MH, Amati P, Mothes D, Bonneau D, Marechaud R, Barbier J. Familial papillary carcinoma of the thyroid. Surgery 1997; 121: 715–8. 2. Ozaki O, Ito K, Kobayashi K, Suzuki A, Manabe Y, Hosoda Y. Familial occurrence of differentiated, nonmedullary thyroid carcinoma. World J Surg 1988; 12: 565–71. 3. Kobayashi K, Tanaka Y, Ishiguro S, Mori T, Mitani Y,
Familial papillary carcinoma of the thyroid Shigemasa M. Family with nonmedullary thyroid neoplasms. J Surg Oncol 1995; 58: 274–7. 4. Bulow S, Holm NV, Mellemgaard A. Papillary thyroid carcinoma in Danish patients with familial adenomatous polyposis. Int J Colorectal Dis 1988; 3: 29–31. 5. Plail RO, Bussey HJ, Glazer G, Thomson JP. Adenomatous polyposis: an association with carcinoma of the thyroid. Br J Surg 1987; 74: 377–80. 6. Malchoff CD, Sarfarazi M, Tendler B, Forouhar F, Whalen G, Joshi V, Arnold A, Malchoff DM. Papillary thyroid carcinoma associated with papillary renal neoplasia: genetic linkage analysis of a distinct heritable tumor syndrome. J Clin Endocrinol Metab 2000; 85: 1758–64.
791
7. Lupoli G, Vitale G, Caraglia M, Fittipaldi MR, Abbruzzese A, Tagliaferri P, Bianco AR. Familial papillary thyroid microcarcinoma: a new clinical entity. Lancet 1999; 353: 637–9. 8. Stoffer SS, Van Dyke DL, Vaden Bach J, Szpunar W, Weiss L. Familial papillary carcinoma of the thyroid. Am J Med Genet 1986; 25: 775–82. 9. Grossman RF, Tu SH, Duh QY, Siperstein AE, Novosolov F, Clarck OH. Familial nonmedullary thyroid cancer: an emerging entity that warrants aggressive treatment. Arch Surg 1995; 130: 892–9. Accepted for publication 28 July 2000
Visits to Departments of Surgical Oncology in Europe As part of the educational role of the European Journal of Surgical Oncology, the Editors have decided to introduce a regular section in EJSO designed for departments of surgical oncology throughout Europe to indicate to our readers their encouragement for visits from trainees (both clinical and research). It is generally understood that persons who are willing to visit the centres have arranged their own funding unless otherwise stated. Any of our readers who would wish to visit the centres should contact the institution to plan the visit in more detail. The Department of General Surgery, Institut Gustave-Roussy, Villejuif, France The Institut Gustave-Roussy is located just outside Paris. The Department of General Surgery is a 102-bed unit with 10 full-time and two part-time surgeons, 12 attendants and residents. One psychotherapist works full-time with the team. Three thousand and four hundred operations a year are carried out in six operating theatres. The range of tumours treated are: gynaecological, gastro-intestinal, hepatic, breast, skin, thyroid, urological, bone and soft tissue. There are several outpatient clinics per week. Surgical staff participate at least once a week in multidisciplinary clinical committees. Surgical staff meet once a week to discuss cases and new protocols. Two foreign residents are part of the staff every six months. The Department is an integral part of the most important cancer institute in France with 507 beds and 700 doctors and research workers. The Department of Surgery, University of Heidelberg, Heidelberg, Germany The Department of Surgery at the University of Heidelberg is a 200 bed unit with special clinical section of Surgical Oncology, Vascular Surgery and Trauma Surgery. The Section of Surgical Oncology was instituted in 1982 to provide facilities for rapid translation of new treatment concepts into clinical practice. The section includes a special, wellstaffed 20-bed unit, an outpatient clinic and a unit for oncological documentation. Special treatment facilities include intraoperative radiation therapy in a dedicated operating suite and isolated extremity perfusion. Major clinical activities concern treatment of oesophageal cancer, liver tumours, retroperitoneal malignancies and treatment of tumour recurrence. Clinical protocols currently under evaluation address IORT for soft tissue sarcoma and rectal cancer, adjuvant treatment of colon cancer, adjuvant immunotherapy following curative resection of colorectal liver metastases and chronomodulated neoadjuvant treatment of advanced liver metastases. Visitors are welcome. If they stay for prolonged time periods and have good command of the German or English language, active participation in the section’s scientific activities is encouraged. Contact: T. Lehnert, MD, Section of Surgical Oncology, Department of Surgery, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. Fax: +49-6221-565506; E-Mail: thomas–[email protected] The Department of Surgery and Surgical Oncology, Robert-Ro¨ssle-Hospital, Charite´, Humboldt University, Berlin, Germany The Robert-Ro¨ssle-Hospital is a 200-bed specialized oncology center and is part of the Charite´ Clinic in Berlin. It is located on the campus of the Max-Delbru¨ck-Center for Molecular Medicine, one of the large central biomedical research facilities in Germany. The Department of Surgery and Surgical Oncology is a 68-bed unit including a highly equipped eight-bed intensive care ward. The most frequently treated tumour entities are GI-tract cancers and hepatic malignancies, breast cancer, thyroid cancer, malignant melanoma and bone and soft tissue sarcoma. Active clinical research protocols are based on hyperthermia, isolated limb perfusion with TNF, and photodynamic therapy, as well as innovative staging procedures in cancer. A special research unit (OP 2000) is engaged in all aspects of telemedicine and computer-aided surgery. There is a close cooperation with basic research groups on the campus with projects in tumour invasion and metastasis, multi-drug resistance, hereditary cancer syndromes and gene therapy. Visitors are welcome. Depending upon knowledge, active participation in the clinical and scientific activities is encouraged. Contact: Prof. Dr P. M. Schlag, Robert-Ro¨ssle-Klinik,Lindenberger Weg 80, 13122 Berlin, Germany. Tel: 0049-309417 1400; Fax: 0049-30-9417 1404; E-mail: [email protected]