[How should we manage a patient with asymptomatic primary hyperparathyroidism?].
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Publications and source records attributed to F Triponez.
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BACKGROUND: Due to the relatively small number of patients involved, there is currently no consensus on what operation should be performed in patients with tertiary hyperparathyroidism after renal transplantation. METHOD: Retrospective analysis of the 70 patients with tertiary hyperparathyroidism who all underwent subtotal parathyroidectomy with transcervical thymectomy in the same institution between 1978 and 2003. RESULTS: The delay between transplantation and parathyroidectomy was 4,1+/-4,3 years. Follow up was available for all patients. Mean follow-up was 5,6+/-5 years. Glomerular filtration rate (GFR) was 53+/-21 ml/min at parathyroidectomy and 42+/-29 ml/min at follow-up [<30 ml/min in 26 patients (37%), 30 - 60 ml/min in 25 patients (36%) et>60 ml/min in 19 patients (27%)]. One patient was successfully reoperated for persistent tertiary hyperparathyroidism during follow-up. No patient was hypercalcemic at follow-up. Four patients with a GFR<30 ml/min had a PTH level>fourfold normal values (6%) without signs or symptoms of hyperparathyroidism. One patient was hypocalcemic (1,5%) and two patients were normocalcemic with undetectable or infranormal PTH level (3%) under oral vitamin D and calcium medication. CONCLUSION: This approach permits not only to cure the majority of patients with tertiary hyperparathyroidism but also to avoid recurrence when the renal function declines. When medical management has failed, we recommend systematic subtotal parathyroidectomy with thymectomy for patients with tertiary hyperparathyroidism and this should usually be performed during the second year after transplantation.
BACKGROUND: There is ongoing controversy as to the indications for and extent of lateral cervical lymphadenectomy for patients with papillary thyroid cancer (PTC). While most now agree that prophylactic lymph node dissections (LND) play no role, at the University of California, San Francisco (UCSF) we limit LND selectively on a level by level basis, and resect only the levels thought to harbor disease or to be at increased risk of metastases. This initial 'selective LND' usually includes levels III and IV (due to the well-documented increased likelihood of metastases to these levels) and levels I, II, and V are included when there is clinical or radiological evidence of disease or increased risk of it. METHODS: A retrospective review of the clinical charts and hospital records of 106 consecutive patients who had metastatic PTC and who underwent at least one lateral cervical LND at UCSF between January 1995 and December 2003 was carried out. Data were collected to assess which patients had levels I, II, and/or V included in their initial ipsilateral and/or contralateral LND and to determine the recurrence rates at these levels if they had previously been excised compared with if they had not. Chi-squared and Fisher exact tests were utilized for statistical comparison, where appropriate. RESULTS: A total of 140 initial lateral LND were performed: 104 ipsilateral and 36 contralateral. In these initial LND, 3.9%, 72.5%, and 18.6% of patients had levels I, II, and V resected on the ipsilateral side, and 2.9%, 60.0%, and 37.1% of patients had levels I, II, and V resected on the contralateral side. Recurrence at levels I and V was uncommon in all patient populations. Recurrence at level II was 19% ipsilaterally and 10% contralaterally when the level was previously resected and 21% ipsilaterally and 14% contralaterally when the level was not previously resected. There was no statistically significant difference in recurrence at level II when the level had previously been resected compared with when it had not. CONCLUSIONS: If utilized in the appropriate patient population, a selective approach to lateral cervical LND for PTC can be a successful alternative to the routine modified radical LND. Levels I and V do not require resection unless there is clinical or radiological evidence of disease. Guidelines for which patients may be considered for this less aggressive approach to level II nodal metastases are suggested.
AIM OF THE STUDY: The allograft of pancreatic islets represents a potential alternative to insulin therapy in patients suffering from the most severe forms of Type 1 diabetes. Here we report our experience of pancreatic procurement for isolation and islet allograft. MATERIALS AND METHODS: Pancreata were procured in brain-dead donors. The islets were isolated using techniques developed and validated in pigs and men. Injection of a given preparation was decided after quantitative and qualitative controls. Islets were transplanted in Type 1 diabetic patients already grafted with a kidney or suffering from severe and/or unstable diabetes, after percutaneous or surgical settlement of an intra-portal catheter. Patients received an "Edmonton-like" immunosuppressive protocol. Grafts were repeated once or twice until a total quantity of 10,000 transplanted islet-equivalents was obtained. RESULTS: Twenty-nine pancreata were procured and 14 preparations were grafted to 7 patients. Eleven graftings were done percutaneously and three were surgical. The initial function of the 14 transplants was confirmed by secretion of C-peptide and decrease of insulin doses. Insulin therapy was completely interrupted in the 5 patients having received at least two grafts. CONCLUSION: These preliminary clinical results confirmed that the isolation technique of human islets and the technique of pancreas procurement are mastered by our team. If the results of this assay (assessment one year after graft) confirm our hopes, we will be able to offer islet allografts to an increasing number of patients with severe Type 1 diabetes.
BACKGROUND: There is currently no consensus on the operation that should be performed in patients with tertiary hyperparathyroidism (HPT) after renal transplantation. METHODS: : A retrospective analysis of 70 patients with tertiary HPT who underwent subtotal parathyroidectomy with transcervical thymectomy was performed. RESULTS: Mean (s.d.) follow-up was 5.6(5.0) years. Mean (s.d.) glomerular filtration rate (GFR) at follow-up was 42(29) ml/min and was less than 30 ml/min in 26 patients (37 per cent), 30-60 ml/min in 25 (36 per cent) and more than 60 ml/min in 19 (27 per cent). One patient had persistent disease and was cured after reoperation. No patient was hypercalcaemic. Four patients (6 per cent) with a GFR below 30 ml/min had a parathyroid hormone (PTH) level more than four times the normal value without any signs or symptoms of secondary HPT. One patient (1 per cent) was hypocalcaemic and two (3 per cent) were normocalcaemic, with undetectable or below-normal PTH levels while receiving oral vitamin D and calcium medication. CONCLUSION: Systematic subtotal parathyroidectomy associated with thymectomy is effective in treating most renal transplant recipients with tertiary HPT and also minimizes the recurrence of HPT in patients with declining renal function.
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AIM: This study has assessed the suitability of an educational concept for the introduction and training of laparoscopic cholecystectomy, a newly established operational procedure, within an university teaching hospital with a large number of surgeons. PATIENTS AND METHODOLOGY: Since introduction of the first laparoscopic cholecystectomy all cholecystectomies were prospectively assessed over a period of two years (from May 1990 till May 1992). The educational concept applied was such that a given surgeon would first receive training from an instructor for 15 procedures and then assume responsibility for instruction of a subsequent trainee. RESULTS: In two years 355 patients underwent cholecystectomy. 60% of the operations were performed laparoscopically and 40% of the operations performed openly. During the two year period 13 surgeons were trained in the new technique, with an average of 16 operations per surgeon. Throughout the introductory phase there were no serious complications, and in particular no damage to the bile duct. DISCUSSION: The advantage of this introductory training phase has repeatedly been subject of discussion in the literature. In the meanwhile guidelines from specialist bodies and national institutions exist for regulating the education of new surgical techniques. In the past few years introduction to new techniques has gradually shifted toward training on the skill-stations and virtual reality trainers. CONCLUSION: The described educational concept for the introduction and training of laparoscopic cholecystectomy has been well approved and accepted since the early 90's.
AIM OF THE STUDY: To study the survival of patients with thyroid cancer operated in the same centre from 1978 to 1999. PATIENTS AND METHOD: This retrospective study included 218 patients operated on for thyroid carcinoma from january 1978 to december 1999. Modified neck dissection was performed only in the presence of one or more suspected lymph nodes. The stage of the cancer was defined according to the last TNM classification (1997). Survival data were taken from the Geneva Tumour Registry (168 patients = 77% of the series, 109 papillary carcinomas, 37 follicular, 14 undifferentiated and 8 medullary carcinomas). RESULTS: The overall 5, 10 and 15-year survival rates were respectively 88%, 84% and 80%. Papillary carcinoma was associated with the best survival at 5, 10 and 15 years (99%, 97% and 93%), despite a recurrence rate of 20% treated mainly by surgery often associated with radioiodine therapy. Follicular carcinoma had a survival rate of 83% at 5 years and 75% at 10 years. Undifferentiated carcinoma had a median survival rate of 56 days. None of the 8 patients with medullary carcinoma had died from that cancer in this series. CONCLUSION: Thyroid carcinoma carries such a good prognosis (except for undifferentiated carcinoma) that invasive surgery at first operation, like radical neck dissection, is not justified, despite a high rate of recurrence.
The replacement of insulin-producing beta cells by islet transplantation can efficiently reverse diabetes. The recent improvements in clinical results were made possible by transplanting higher islet masses and through the introduction of new immunosuppressive protocols that avoid diabetogenicity. The need for alternatives to continuous immunosuppression, and an unlimited source of glucose-sensitive, insulin-secreting tissue, is emerging. In this review we discuss the various key steps in islet transplantation and offer perspectives for future developments in the replacement of insulin-producing beta cells for the treatment of type I diabetes.
BACKGROUND: A series of 13 islet autotransplantations and 13 islet allotransplantations performed between 1992 and 1999 at the University Hospital of Geneva are presented. Factors affecting the outcome are analyzed. METHODS: Islet autotransplantation has been performed in seven patients with chronic pancreatitis and in six patients with benign tumors undergoing extensive pancreatectomy. Islet allografts were performed in C-peptide-negative patients simultaneously or after a kidney or lung transplantation. Each recipient received islets from one to four donors. Panel-reactive antibodies were monitored by microlymphocytotoxicity test. RESULTS: Eleven of 13 patients who underwent autotransplantation maintained insulin independence for 6 months to 5 years. Two years after autologous islet transplantation, five of nine patients were insulin independent with an glycosylated hemoglobin of 5.9%. Three late islet failures occurred in patients with chronic pancreatitis. Islet yield was significantly lower in patients with chronic pancreatitis than in patients with benign tumors (2044 equivalent islet number/gram resected pancreas versus 5184 equivalent islet number/gram; P=0.037). In islet allotransplantation, no early graft loss was found. All 13 patients who underwent allotransplantation had basal C-peptide levels above 0.3 nmol/L for 3 months to 5 years. Mean glycosylated hemoglobin decreased from 9.1% before transplantation to 5.5% at month 3. Insulin independence was achieved in two type I diabetic patients. In four of six patients with graft failure, the graft had induced panel-reactive antibodies. CONCLUSIONS: In islet autotransplantation, the reduced number of islets that can be isolated from fibrotic pancreata may be the major limiting factor. In islet allotransplantation, early graft function can now be consistently achieved. Islet allografts seem to be highly immunogenic, and chronic islet failure cannot be prevented consistently by conventional immunosuppression.
CD8(+) cytolytic T lymphocytes (CTL) play a fundamental role in the clearance of malaria parasites from the liver in mouse models. In humans, however, only low levels of parasite-specific CD8(+) T lymphocytes have been observed in individuals living in endemic areas. In the present study, we identified high levels of circulating CD8(+) T lymphocytes specific for a previously described HLA-A2-restricted CTL epitope of the circumsporozoite (CS) protein of Plasmodium falciparum in an adult living in Burkina Faso, as evidenced by IFN-gamma ELISPOT assay and MHC-tetramer technology. After cloning by limiting dilution culture, T cell recognition of natural CS variants of P. falciparum was studied. The results demonstrate that naturally occurring variations drastically affect residues critical for T cell recognition as only two out of nine sequences analyzed were efficiently recognized by the CTL clones. These clones were also used to analyze T cell recognition of the endogenously presented cognate antigen. We observed efficient antigen recognition of both HLA-A*0201-transfected murine antigen presenting cells and liver cells from HLA-A*0201/K(b)-transgenic mice upon infection with recombinant vaccinia virus encoding the CS protein (WR-CS). More importantly, we demonstrate for the first time efficient recognition of WR-CS-infected human liver cells.
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Xenogeneic islets could provide an unlimited source of tissue for the treatment of diabetes, and could in theory be transplanted repeatedly in a recipient. However, little is known on the consequences of islet re-transplantation in a recipient who has rejected a first graft. In this study, we investigated the functional consequence of xeno islet re-transplantation in mice sensitized with islets from different species. Sprague-Dawley (SD)-rat islets transplanted in sensitized C57/Bl6 mice that rejected either SD- or Lewis-rat islets underwent accelerated rejection. However, accelerated rejection was not found in mice sensitized with pig or human islets, suggesting that accelerated rejection was species specific. Immunohistochemistry showed increased binding of antibodies and accelerated leucocyte infiltration on re-grafted islets in sensitized mice. In situ apoptosis detection indicated that islet cell apoptosis was correlated with the time of leucocyte infiltration, but not with the time of antibody binding. In vitro experiments with cultured islet cells showed that although antibody binding was increased after incubation with sensitized mouse serum, islet cell cytotoxicity was not increased, suggesting that humoral immunity did not play a direct role in islet destruction. These results indicate that there is a cell-mediated, species-specific accelerated rejection after re-transplantation of xenogeneic islets.
For decades, the inability of insulin therapy to physiologically control glycemia in type I diabetic patients has motivated the search for insulin-delivering grafts. Islet autotransplantation is such a therapeutic approach to prevent diabetes mellitus following a major pancreatectomy, whereas allotransplantation is generally prescribed for type I diabetic patients with a functional solid organ graft, or for patients awaiting one. As of today, over 150 patients have been autotransplanted world-wide, following total or subtotal pancreatectomy, permitting an insulin-independence in nearly 40% of patients. Furthermore, more than 350 islet allotransplantations have been performed. Recent results show improved metabolic control in over 50% of cases and insulin-independence in approximately 20%. This chapter presents a literature review including preliminary human islet transplantation data from the University of Geneva.
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Although the involvement of complement in hyperacute rejection of xenotransplants is well recognized, its role in rejection of devascularized xenografts, such as pancreatic islets, is not completely understood. In this study, we investigated whether complement participates in the immunopathology of xeno-islet transplantation in a concordant rat to mouse model. Rat pancreatic islets were implanted under the kidney capsule of normal and cobra venom factor (CVF)-decomplementized diabetic C57BL/6 mice. Graft survival was monitored by blood glucose levels. Deposition of IgM and C3 on grafted islets in vivo or on isolated islets in vitro (after incubation with normal and decomplementized mouse serum), as well as CD4- and CD8-positive leucocyte infiltration of grafts, was checked by immunohistochemistry. In addition, complement-mediated cytotoxicity on rat islet cells was evaluated by a 3-(4, 5-dimethythiazolyl)-2.5-diphenyl-2H-tetrazolium-bromide (MTT) assay. A significant C3 deposition was found on grafted islets from the first day after transplantation in vivo, as well as on isolated islets after incubation with mouse serum in vitro. By MTT assay, complement-mediated cytotoxicity for islet cells was found. Decomplementation by CVF decreased C3 deposition on either isolated or grafted islets, delayed CD4- and CD8-positive leucocyte infiltration, led to significant inhibition of complement-mediated cytotoxicity for islet cells, and prolonged graft survival (mean survival time 21.3 versus 8.5 days; P<0.01). Our results indicate that decomplementation can prolong the survival time of devascularized xenografts across concordant species. The deposition of complement on transplanted islets may contribute to xenograft rejection by direct cytotoxicity and by promoting leucocyte infiltration.