RET proto-oncogene genetic screening of families with multiple endocrine neoplasia type 2 optimizes diagnostic and clinical management in China.

BACKGROUND: Genetic screening for germline mutations in the RET proto-oncogene has been extensively exploited worldwide to optimize the diagnostic and clinical management of multiple endocrine neoplasia type 2 (MEN2) patients and their relatives. However, a distinct lag period exists not only in the recognition but also in the medical treatment of patients with MEN2. Here we present a comprehensive genetic and clinical analysis of MEN2 among Chinese families followed from 1975 to 2011. Our series comprises 36 index cases and 134 relatives from 11 independent families. METHODS: Genetic diagnosis was performed in all participants by direct sequencing all relevant RET exons. Thyroidectomy was performed in 50 patients with varying cervical neck dissection procedures. Patients with pheochromocytoma (PHEO) underwent specific surgery. Demographic, clinical profiles, mutation types, tumor histopathologic features, and follow-up records were systematically analyzed. RESULTS: The RET mutations p.C634Y (n=34), p.C634R (n=6), p.C618S (n=13), p.V292M/R67H/R982C (n=7), p.L790F (n=2), and p.C634Y/V292M/R67H/R982C (n=1) were confirmed in 31 index cases and then identified in 32 at-risk relatives (mutation carriers), with MEN2A as the most common clinical subtype. The overall penetrance of PHEO in patients with MEN2A was 46.7%. A total of 50 patients underwent thyroidectomy, and there was a significant lowering of their mean age at thyroidectomy and the tumor diameter of the mutation carriers that were detected and operated on compared with the index cases (age at first surgery: 29.3 vs. 39.3 years, p<0.05; maximum size: 1.1 vs. 3.3 cm, p<0.001). There was also a decrease in the TNM staging and the proportion of patients who underwent inappropriate initial thyroid surgery (pN1: 31.6% vs. 100%, p<0.001; inappropriate surgery: 0% vs. 29%). Meanwhile, disease-free survival (DFS) increased (DFS: 100% vs. 58.1%, p<0.05). Both medullary thyroid carcinoma-specific (n=1) and PHEO-specific (n=5) deaths were reported during the study period. CONCLUSIONS: Our results further substantiate that gene scanning of all relevant RET exons is a powerful tool in the management of MEN2 patients, especially in asymptomatic carriers, and has led to earlier diagnosis and more complete initial treatment of patients with MEN2 in China.

Marital status and fertility of 185 male renal transplant recipients in China.

A questionnaire was designed to assess the effects of renal transplantation in men of reproductive age on marital status and fertility. The study sought to correlate recipients' marital status and fertility with the health of the recipients after the transplantation, the health of children they fathered after the procedure, and the functioning of the transplanted kidney. Male recipients (n = 243) who were single and of reproductive age before renal transplantation were selected from 2007 recipients of a renal transplant recorded in the authors' hospitals in China. Of the 243 surveyed, 185 completed the questionnaire and participated in follow-up in the clinic or by telephone. Their marital status and fertility were investigated. Of the 185 recipients, 69 got married 12-88 months (mean, 32.19 +/- 14.30 months) after renal transplantation, and 62 of 69 couples were actively attempting to become pregnant. Fifty-three patients fathered 54 children, including 1 pair of twins, 9-72 months (mean, 25.81 +/- 15.33 months) after marriage. The birth weights of the newborns ranged from 2500 to 4600 g (mean, 3395 +/- 456.80 g). These children developed well. Nine patients did not father any children, and 3 of these 9 cases were attributable to infertility in the wife. Seven patients were using contraceptives. Three recipients suffered from chronic graft rejection and resumed hemodialysis 2-11 years after they fathered children. In addition, 2 patients died after fathering 1 child: 1 from dysfunction of the transplanted kidney 9 years after birth of his child, and another in an accident 1 year after his child's birth. Our findings suggest that, like men without renal transplants, male recipients of renal transplants can get married and father children, and the transplantation procedure appears to have no significant effect on the children fathered afterwards, on the recipients' health, or on the functioning of the transplanted kidney. It is very important to indicate that, in addition to needing contraception if they do not conceive, male renal transplant recipients should expect fertility rates that are similar to those of the general population.

Morphological characteristics of spermatozoa before and after renal transplantation.

AIM: To investigate the changes of the spermatozoa ultrastructures before and after renal transplantation in uremic patients. METHODS: The sperm of five uremic patients before and after transplantation and four healthy volunteers were collected and examined by scanning electron microscopy. RESULTS: Abnormal spermatozoa were found in patients pre-transplantation; abnormalities included deletion of the acrosome, absence of the postacrosomal and postnuclear ring, dumbbell-like changes of the head, tail curling, and absence of the mitochondrial sheath in the mid-segment. After renal transplantation, most of the spermatozoa became normal. CONCLUSION: There are many abnormalities with regard to the appearance and structure of the head, acrosome, mitochondria and tail of the spermatozoa in uremic patients. The majority of the spermatozoa returned to normal after renal transplantation, but a few still presented some abnormalities possibly relating to the administration of immunosuppressants.

[A comparative study of male patient's sexual function before and after kidney transplantation].

OBJECTIVES: To investigate sexual function before and after kidney transplantation in patients with chronic nephrosis. METHODS: Eighty-six male patients were divided into 3 age groups: young-age group (Group A), middle-age group(Group B) and elder-age group(Group C). Sexual function, including potency, frequency and satisfaction of intercourse before and after the sickening, and after transplantation, were recorded in each group. RESULTS: All the patients were potent before suffering from nephrosis. The proportion of patients who were potent after catching the disease in Group A, B and C was 28.6%, 13.8% and 9.1%, respectively. Notably, the proportion of patients remaining potent after transplantation in Group A, B and C was 88.6%, 75.9% and 63.6%, respectively. CONCLUSIONS: Quality of sexual life is significantly improved after kidney transplantation. The younger the patients, the better the improvement.

[Effects of different dosages of cyclosporine A on the semen parameters of renal transplant patients].

OBJECTIVES: To evaluate the effects of different dosages of cyclosporine A (CsA) on the main semen parameters and sperm morphology of the patients after renal transplantation. METHODS: The semen of 18 patients after renal transplantation treated with different dosages of CsA was analyzed and the semen parameters and sperm morphology were compared with those of 12 normal volunteers. RESULTS: There was not significant difference between the main parameters of the patients treated with 1.5-3.0 mg.Kg-1.d-1 of CsA and 3.1-5.5 mg.Kg-1.d-1 of CsA and those of the volunteers (P > 0.05), but the rate of normal sperm morphology was significantly different between the two groups(P < 0.05). CONCLUSIONS: Different therapeutic dosages of CsA did not have any effect on most of the semen parameters of the patients after renal transplantation, but did affect the sperm morphology.