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Biomedical subjects

Yu Seun Kim

Publications and source records attributed to Yu Seun Kim.

35 records · Page 2Linked to original sources

Complete resolution of posttransplant lymphoproliferative disorder (diffuse large B-cell lymphoma) with reduction of immunosuppressive therapy.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. PTLD is the disorder arising from the combined effects of Epstein-Barr virus associated lymphoid proliferation with the disruption of the normal immune control by the cytotoxic T cells. The treatment for PTLD is one of the most controversial topics in solid organ transplantation. It is well known that the initial management of PTLD is a reduction of immunosuppression. Early diagnosis and the early reduction in immunosuppression are essential even for monomorphic lymphoma. We report here on a case of the complete resolution of PTLD (diffuse large B cell lymphoma) which occurred after a drastic reduction of immunosuppression in a renal transplant recipient.

Adult↗

Favorable outcomes among recipients of living-donor nephrectomy using video-assisted minilaparotomy.

BACKGROUND: Minimally invasive, living-donor nephrectomy (LDN) is an attractive procedure for the donor in kidney transplantation (KTx). Its advantages include better cosmesis, shorter hospital stay, and rapid recovery. The most commonly performed, minimally invasive nephrectomy is done laparoscopically. However, the technical challenges, a steep learning curve for the surgeon, the risk of impaired early graft function, and the high cost of the procedure, have prevented minimally invasive LDN from gaining wide acceptance. To overcome these problems, we have developed a new surgical procedure named video-assisted minilaparotomy (VAM) for LDN. VAM-LDN is performed entirely with a small retrieval incision. Moreover, it does not require the induction of pneumoperitoneum, thereby avoiding potential vascular and renal complications. METHODS: We evaluated the outcome of transplant recipients receiving kidneys with the VAM-LDN procedure by retrospectively comparing the surgical outcomes of patients who underwent KTx with the conventional open nephrectomy (group I, n=82) and VAM-LDN (group II, n=70) procedures from March 1, 1997, to June 30, 2002, at our institution. We compared postoperative complications, patient and graft survival, and graft functions between these two groups during a 12-month follow-up period. RESULTS: There were no differences in demographic data, ABO compatibility, degree of human leukocyte antigen matching, or method of immunosuppression between the two groups (P >0.05). No significant difference was observed in complications such as delayed graft function, acute rejection, ureter complication, graft failure, or patient's mortality. There was no difference in graft function between the two groups, as determined by serum creatinine level measured during the 12-month follow-up. CONCLUSION: The short-term recipient outcome was favorable in patients who underwent KTx with the VAM-LDN procedure.

Adult↗

The evolution of lupus activity among patients with end-stage renal disease secondary to lupus nephritis.

The aim of this study was to evaluate the evolution of lupus activity in end-stage renal disease (ESRD) patients due to lupus nephritis and to determine the long-term prognosis. We reviewed the clinical courses of 45 patients with ESRD due to systemic lupus erythematosus (SLE). We analyzed the course of SLE following the onset of ESRD, with special attention to the clinical and serological manifestations, survival time on dialysis, and renal transplantation outcome. Disease activity was measured using the SLE Disease Activity Index (SLEDAI). Of the 45 patients, 21 patients were being treated with hemodialysis (HD), 11 were undergoing peritoneal dialysis (PD), and 13 underwent transplantation. Duration of follow- up was 53 +/- 29 months. The SLEDAI score on commencement of renal replacement therapy was not significantly different among the 3 groups (HD: 4.2 +/- 4.2, PD: 4.3 +/- 2.3, Transplant: 3.2 +/- 1.9). However, disease activity scored by follow-up maximal SLEDAI during dialysis or transplantation showed a significant increase after peritoneal dialysis (HD: 5.0 +/- 3.6, PD: 7.4 +/- 3.7, Transplant: 2.2 +/- 1.7, p < 0.05). When the individual changes in the maximal SLEDAI score were considered, a significant increase was apparent after peritoneal dialysis (p < 0.05), but not after either hemodialysis or renal transplantation. There was no significant difference in cumulative survival rate, and also in technique or graft survival rates of the 3 groups. Among the variables tested, follow-up maximal SLEDAI score was the only significant factor associated with patient survival (odds ratio: 1.15, p < 0.05). The incidence (36% versus 19%) of high disease activity was greater, but not significantly, in the peritoneal dialysis group, as compared to the hemodialysis group. Clinical activity of SLE was apparent in 65% of patients in the first year of dialysis, but none showed any activity after the third year of dialysis. We found that although lupus disease activity declined after patients progressed to ESRD, lupus disease activity still affected patients' survival. An incremental increase in postdialysis lupus activity was not uncommon, especially during the first one year of dialysis. During the follow-up period, maximal SLEDAI score increased significantly after peritoneal dialysis. However, the long-term prognosis was not significantly different according to the treatment modality.

Adult↗

Hepatitis B virus infection after renal transplantation in the presence of antibody to hepatitis B surface antigen immunity.

BACKGROUND AND AIM: Hepatitis B virus (HBV) infection has been known to be hampered by immunity against hepatitis B surface antigen (HBsAg). However, HBV with mutations within the common antigenic epitope of HBsAg, the "a" determinant region, can escape from humoral immunity. Moreover, HBV infection by "a" determinant mutants in chronic HBV patients has been reported after renal transplantation. In the present study, the authors investigated HBV infection after renal transplantation despite passive immunization or resolved HBV infection. METHODS: A total of 1682 patients who underwent a renal transplant between 1979 and 1998 at the Severance Hospital, Yonsei University College of Medicine, Korea, were enrolled. The sequence of the HBV genome was analyzed from two patients with antibody to HBsAg (anti-HBs) immunity. RESULTS: Of 1682 patients who were HBsAg negative before transplantation, 21 patients were found to be HBsAg positive, with elevated aspartate aminotransferase and alanine aminotransferase levels after transplantation. Interestingly, six of 21 (28.6%) patients were anti-HBs positive before the transplantation. Sequence analysis of the cloned HBV from two of six patients with anti-HBs immunity showed no evidence of significant mutations within the "a" determinant region, suggesting a wild-type of HBV. Their donors were not exposed to HBV before transplantation (all HBV markers were negative). Seven deaths of 21 patients were ascribed to HBV-related complications. CONCLUSIONS: Regardless of anti-HBs immunity, HBV infection occurred in immunosuppressed patients in a high endemic area. The molecular mechanism and clinical impact of HBV infection after renal transplantation in patients with anti-HBs immunity should be further reappraised.

Adult↗

Glomerular crescents are responsible for chronic graft dysfunction in post-transplant IgA nephropathy.

Information is limited regarding the histological features related to chronic graft dysfunction and failure in patients with IgA nephropathy developing after renal transplantation. The prevalence and significance of glomerular crescents in post-transplant IgAN including recurrent, de novo and transmitted forms (TxIgAN), were studied. Renal morphology was evaluated in 71 patients of TxIgAN, obtained at more than 6 months post-transplant, and compared with regard to the presence (C-TxIgAN) or absence (N-TxIgAN) of glomerular crescents. Crescents were demonstrated in 12 samples of 10 patients (14.1%). The percentages of crescents were from 4.8% to 83.3% (median, 28.6%) in each sample. Ten samples of C-TxIgAN had cellular to fibrocellular crescents, and four of these were associated with diffuse mesangial proliferation. Serum creatinine levels and the frequency of nephrotic range proteinuria at the time of biopsy and the degree of interstitial inflammation were significantly different in the two groups. Graft survival after allograft biopsies was significantly lower in C-TxIgAN (P = 0.0017). Chronic rejection was a major cause of graft loss in N-TxIgAN (31.8%), whereas TxIgAN was the major cause in C-TxIgAN (66.7%). In conclusion, the current study suggests that glomerular crescents are not rare and that they are responsible for chronic graft dysfunction in TxIgAN patients.

Adult↗

Mycophenolic acid inhibits platelet-derived growth factor-induced reactive oxygen species and mitogen-activated protein kinase activation in rat vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) proliferation is the major pathologic feature associated with chronic allograft nephropathy, and mycophenolic acid (MPA) inhibits VSMC proliferation. Since the role of inosine monophosphate dehydrogenase (IMPDH)-dependent de novo guanosine synthesis is limited in VSMCs, we examined the effects of MPA on platelet-derived growth factor (PDGF)-induced cellular ROS and mitogen-activated protein kinases (MAPK) activation in VSMCs. Primary cultured rat VSMCs were stimulated with PDGF-BB in the presence or absence of MPA. Cell proliferation was assessed by [3H]-thymidine incorporation, ROS by flow cytometry and MAPK activation by Western blot analysis. PDGF increased cell proliferation, cellular ROS and extracellular-regulated protein kinase (ERK) 1/2 and p38 MAPK activation by 3.4-, 1.6-, 3.3- and 3.9-fold, respectively. MPA at above 1 muM inhibited PDGF-induced cellular ROS and ERK 1/2 and p38 MAPK activation, as well as proliferation. Structurally different anti-oxidants and inhibitor of ERK or p38 MAPK blocked PDGF-induced proliferation. Anti-oxidants also inhibited ERK 1/2 and p38 MAPK activation. Exogenous guanosine partially recovered the inhibitory effect of MPA on VSMC proliferation. These results suggest that MPA may inhibit PDGF-induced VSMC proliferation partially through inhibiting cellular ROS, and subsequent ERK 1/2 and p38 MAPK activation in addition to inhibiting IMPDH.

Animals↗

Reactive oxygen species mediate TGF-beta1-induced plasminogen activator inhibitor-1 upregulation in mesangial cells.

Transforming growth factor-beta1 (TGF-beta1) promotes tissue fibrosis by upregulating genes encoding extracellular matrix proteins and by increasing the synthesis of plasminogen activator inhibitor-1 (PAI-1). TGF-beta1 induces cellular reactive oxygen species (ROS) and PAI-1 promoter region has binding sites for redox sensitive transcription factors. We, therefore, hypothesized that TGF-beta1-induced upregulation of PAI-1 is ROS-dependent. Using cultured glomerular mesangial cells, we confirmed that TGF-beta1 induces cellular ROS, upregulates PAI-1 mRNA and protein expression, and suppresses plasmin activity. We further demonstrated that H(2)O(2) stimulates PAI-1 expression and suppresses plasmin activity and that N-acetylcysteine effectively reverses TGF-beta1- and H(2)O(2)-induced changes in PAI-1 expression and plasmin activity. Basal as well as TGF-beta1- and H(2)O(2)-induced PAI-1 expression was upregulated by depletion of intracellular GSH. The present data demonstrate that TGF-beta1-induced PAI-1 in mesangial cells is ROS-dependent and imply that cellular ROS may be potential therapeutic targets in glomerular fibrosis.

Animals↗

Comparative study of renal replacement therapy in Korean diabetic end-stage renal disease patients: a single center study.

The number of diabetic ESRD patients has increased and death rates of diabetic patients on hemodialysis (HD), peritoneal dialysis (PD) and renal transplantation (RT) have remained higher than the death rate of non-diabetic patients. An attempt was made to compare the clinical characteristics, patients' cumulative survival, and technical survival among the three groups retrospectively according to the mode of renal replacement therapy(RRT), and to analyze the risk factors associated with mortality. A total of 229 diabetic ESRD patients diagnosed between 1986 and 1995 at the Severance Hospital who began dialysis or who underwent a kidney transplant were included and their medical charts were reviewed. Hypertension was the most common co-morbid disease in all study groups. The prevalence of cardiovascular disease was the only co-morbid condition that was significantly different among the three groups, which was highest in the PD group (24.4%) and lowest in the RT group (8%). In the analysis of a patient's cumulative survival rate not adjusted for age and sex, the RT group had the highest survival rate, and the cumulative survival rate of the HD and PD group were similar. The 5-year survival rate of the patients treated with HD, PD and RT was 28.8%, 19.8%, and 72.0%, respectively. No differences were observed in the patient's cumulative survival rate between the HD and PD patients even when it was adjusted for age. When adjusted for age, sex and risk factors, the relative death rate of the RT group was significantly lower in male patients younger than 60 years of age. With the exception of male patients younger than 60 years of age, the PD group showed a slightly lower relative death rate although it was not significant. The multiple Cox regression analysis of patient survival showed that age, serum albumin, BUN, mean hospital days, the presence of cardiovascular disease at the initiation of RRT were associated with mortality. The analysis of the technique survival rate revealed a better result in the HD group compared to PD group, but a limitation in being able to investigate the AVF function disturbed the accuracy of the analysis of technical survival rate. In conclusion, the survival rate between the PD and HD patients was not different and the RT group had the best survival rate. Therefore, kidney transplantation in diabetic ESRD patients should be considered positively if no other contraindicated condition for RT exit.

Aged↗

Polyomavirus nephropathy in renal transplantation: a clinico-pathological study.

Polyomavirus (PV) nephropathy is a rare cause of graft dysfunction, but it may accompany acute rejection (AR), resulting in complications with respect to its diagnosis and treatment. To examine the validity of tubulitis and inflammatory phenotype in the diagnosis of concurrent AR, we reviewed the renal histology of ten biopsy samples from nine patients with PV nephropathy, and the immunohistochemistry from eight samples. Tubulitis was present in seven patients and was associated with AR in six. The degrees of tubulitis and interstitial inflammation were higher in biopsy samples with AR than in those without, but the degree of tubulitis was not related to the degree of interstitial inflammation. Virally infected cells were rare in the samples with no, or mild, tubulitis, but did not increase with the degree of interstitial inflammation. Immuno-phenotyping of inflammatory cells did not show any T-cell dominance in AR: T cells were dominant over B cells in three of six samples with AR and both samples without AR. Although the degrees of tubulitis and interstitial inflammation were higher in the AR subjects, the presence of tubulitis or inflammatory phenotype was not helpful in the diagnosis of concurrent AR. Further studies will be required to find a better marker for coexisting AR in patients with PV nephropathy and to establish strategies for treatment.

Acute Disease↗

Segmental glomerulosclerosis in IgA nephropathy after renal transplantation: relationship with proteinuria and therapeutic response to enalapril.

INTRODUCTION: Although graft dysfunction has been increasingly reported in post-transplant IgA nephropathy (Tx-IgAN), intragraft morphological changes have been largely overlooked. We evaluated glomerular changes in Tx-IgAN to identify the histological features pertaining to significant proteinuria and therapeutic response to enalapril. MATERIALS AND METHODS: Fifty-four renal allograft biopsies, diagnosed as Tx-IgAN at a median of 46 months after transplantation, were the subject of the study. In 10 patients, glomerular morphometry was performed. In 14 patients who have been treated with enalapril for more than 12 months, we correlated the therapeutic response to enalapril with allograft histology. RESULTS: No uniform pattern was found in the glomeruli of Tx-IgAN. The glomerular mesangium was mostly indistinct. Interstitial fibrosis was negative or mild in 88.9%. By morphometry, the glomerular tuft areas and mesangial areas were significantly larger in Tx-IgAN than those of the normal native kidney (p < 0.05), but were not different from transplant cases without glomerulonephritis. Proteinuria of >/=1 g/24 h was correlated with glomerulosclerosis, interstitial fibrosis and interstitial inflammation at time of biopsy (p < 0.005). The presence of segmental sclerosis (SS) correlated well with the amount of 24-h proteinuria (p < 0.001). After treatment with enalapril, the amount of proteinuria reduced in 64.3%. Therapeutic response to enalapril tended to be less effective in patients having SS (28.6 versus 71.4%), but this finding did not reach a statistical significance. CONCLUSIONS: Significant proteinuria was associated with advanced chronic injury, especially with the presence of SS in Tx-IgAN, but anti-proteinuric effect of enalapril was not affected by graft histology. It remains to be clarified whether glomerular mesangial expansion plays a role in graft dysfunction in a subset of Tx-IgAN showing prominent mesangial changes.

Adult↗

Kidney transplantation in Yonsei University from 1979-2003.

1. Long-term graft survival has been markedly improved after the introduction of CsA microemulsion and FK-506 as our main immunosuppressants, and the use of triple maintenance immunosuppression including MMF in living-donor kidney transplantation (KTX) at Younsei University. 2. The risk factors affecting long-term graft survival in living-donor KTX were recipient and donor age, type of immunosuppression including regimen, presence of pretransplant diabetes or hepatitis B, and the development of acute rejection after KTX. 3. The long-term graft survival rate with living-unrelated donor KTX was comparable to that with HLA-haploidentical living-related donor KTX. 4. Because of the striking disparity between organ donation and the increasing demand for KTX, distant relatives, living unrelated donors (including swap donors) should be considered as an alternative approach to increasing the number of available donors when accompanied by a careful evaluation process. 5. We recommend the use of minimally invasive approaches to donor nephrectomy to increase the rate of living donor donation. 6. We recommend negative lymphocyte crossmatch conversion protocols for patients with a positive crossmatch against their potential living donor.

Adult↗

Evidence that the ratio of donor kidney weight to recipient body weight, donor age, and episodes of acute rejection correlate independently with live-donor graft function.

BACKGROUND: We demonstrated that higher donor kidney weight-to-recipient body weight (KW/BW) ratio showed better graft function in acute rejection-free renal recipients. METHODS: We investigated the impacts of KW/BW ratios on the graft function including acute rejection and donor's age in 259 live-donor renal recipients. Renal parameters were measured yearly. Correlations between the variables and each parameter were assessed by mixed regression and analysis of variance. RESULTS: Renal function showed a positive correlation with the KW/BW ratio, but an inverse correlation with the rejection episodes and donor's age. The regression slope for serum creatinine or creatinine clearance by these covariants was consistent each year. On comparing the lower KW/BW ratios (<3.0) with higher ratios (> or =4.5), the higher was associated with better graft function. Increased donor's age was associated with worse graft function. CONCLUSIONS: KW/BW ratio, donor's age, and the number of acute rejections are independent covariants for graft function.

Adult↗

Effects of carvedilol alone and in the presence of cyclosporine A on the DNA synthesis of cultured vascular smooth muscle cells.

PURPOSE: There is still no reliable method of preventing or treating chronic rejection or transplant vascular sclerosis. A recent in vitro cell culture study showed that carvedilol significantly inhibited the proliferation of vascular smooth muscle cells (VSMCs); however, the effect of carvedilol in the presence of cyclosporine (CsA) has not yet been reported. Using in vitro cultured VSMCs, we measured the antiproliferative activity of carvedilol alone and in combination with CsA. METHODS: Growth-arrested cultured VSMCs from the thoracic aorta of Sprague-Dawley rats were exposed to platelet-derived growth factor (PDGF)-BB, endothelin (ET)-I, and angiotensin (ANG)-II. Carvedilol (1 and 10 microM) and/or CsA (100 nM) were added as test drugs. DNA synthesis was assessed by measuring the incorporated [3H]thymidine activity, and the percentage of inhibition in the presence of the test drugs was determined. RESULTS: Compared with the PDGF-stimulated control, DNA synthesis decreased significantly to 60.3% +/- 10.4% and 18.3% +/- 5.9% in the presence of 1 and 10 microM of carvedilol, respectively (P < 0.05, each). Carvedilol significantly inhibited the activity of VSMCs stimulated by ET-1 and ANG-II. The IC50 of carvedilol was 1-10 microM. CsA only inhibited VSMCs significantly in the PDGF-stimulated subgroup. The addition of CsA in the presence of carvedilol did not affect the inhibitory activity of carvedilol. The pattern of inhibition in the combined group was uniform and similar to that of the carvedilol alone group, regardless of the stimulator used. CONCLUSION: Carvedilol significantly inhibited the DNA synthesis of VSMCs regardless of the kind of stimulators examined, even in the presence of CsA. These results indicate that carvedilol has the unique potential to inhibit the development of transplant vascular sclerosis in hypertensive transplant recipients under CsA-based immunosuppression.

Animals↗

Live donor partial liver harvest for canine liver transplantation: development of an innovative technique for surgical training and research.

PURPOSE: Most models of canine segmental liver transplantation use about 40% of the total liver volume including the left lateral and medial segments, an approach which is associated with some shortcomings. First, during live donor harvest, a necrotic segment requiring further resection is unavoidable after removal of the donor segments; and second, to harvest the left lobe, two dissection planes must be used. This creates some technical bias and limitations in designing a canine research model. Herein, we report a new technique of harvesting up to 70% of the liver in dogs. METHODS: The right medial and quadrate segments, the left lobe, and the papillary process of the caudate lobe were resected and harvested for transplantation. We divided the middle hepatic vein to enable a single parenchymal dissection between the right medial and lateral segments and no perfusion defect was seen. Using this technique, we performed orthotopic autoauxiliary transplantation ( n = 6) and orthotopic alloauxiliary transplantation ( n = 5) in dogs. RESULTS: All dogs transplanted with an autograft were alive at the completion of surgery. All donor dogs providing 70% of the liver volume for allografts were alive 1 week after surgery, and all five allograft recipient dogs were alive 48 h after surgery, at which point they were killed. CONCLUSIONS: This novel experimental technique of partial living donor liver transplantation using about 70% of the liver allows for easier harvest and effective live donor partial liver transplantation. Moreover, the fact that division of the liver parenchyme can be done without leaving a necrotic segment shows the possibilities for various research models of ischemic-reperfusion injury. This technique allows us to divide the liver in situ, then subject the right segment of the liver to various insults or remedies for comparison.

Animals↗

Diffuse glomerular basement membrane lamellation in post-transplant IgA nephropathy.

Diffuse glomerular basement membrane (GBM) lamellation, reminiscent of Alport's syndrome, has rarely, and exclusively, been reported in renal allografts from pediatric donors to adult recipients. We report on a similar lesion, identified in a 42-year-old male, who received a kidney from an unrelated 21-year-old living male donor. The disease of the recipient was unknown. Renal allograft biopsies were performed 3.5 and 4.8 years after the renal transplantation, due to massive proteinuria and serum creatinine elevation. The histological features of both biopsies were similar, but more advanced in the second biopsy. Glomerular mesangium was widened and had an IgA deposit in the first biopsy. In addition to the presence of mesangial electron dense deposits, the GBM showed diffuse lamellation and splintering on the subepithelial side, but no definite deposits. In the second biopsy, IgA deposits were extended to the peripheral capillary walls, but electron microscopic examination was not available. Two months after the second biopsy, the patient returned for hemodialysis.

Adult↗

Gender-related differences of renal mass supply and metabolic demand after living donor kidney transplantation.

Kidney donation from female donors to male recipients has been reported to be associated with decreased allograft survival. Whether there was a gender-related inadequacy between donor nephron supply and recipient functional demand was investigated in this study. One hundred ninety-five living donor kidney transplant recipients that had neither ischemic injury, episode of rejection, nor any complication were included. Weights and heights of both donors and recipients were recorded to calculate body surface area, lean body weight, and body mass index. The donated kidney was weighed just after cold flush, and the recipient's serum creatinine (Scr) was measured on a daily basis post-operatively. When the recipient's Scr reached the baseline, a 24-h urine was collected for the amount of proteinuria (Upr), creatinine excretion (Ucr) and creatinine clearance (Ccr) calculation. The effect of donor and recipient gender was analysed by independent sample t-test. On average, male donors and recipients were heavier and taller than females. However, the mass of kidneys donated from men and women were not statistically different. The gender-related differences in post-transplant Scr and Ucr of recipients were associated with the differences in the parameters of metabolic demands of recipients rather than with the weight of implanted kidney (renal mass supply) or with pre-operative renal functions of donors (functional supply). The early graft function is not determined by donor gender. The effect of recipient gender on the graft function depends on the metabolic demands, which are higher in male recipients.

Adult↗

Gastric adenocarcinoma after renal transplantation.

BACKGROUND/AIMS: Little is known of the characteristics of gastric adenocarcinoma after renal transplantation. This study was performed to find out the incidence and clinicopathological features of gastric adenocarcinoma after renal transplantation in an endemic area for gastric cancer. METHODOLOGY: Between April 1979 and March 2001, fourteen gastric adenocarcinoma patients (0.7%) out of 2000 renal transplant recipients in a single institute were retrospectively reviewed. RESULTS: Gastric adenocarcinoma was identified in 14 recipients (8 males and 6 females; mean age 47.6 years) about 60 months after renal transplantation. Four patients had early gastric cancer; ten patients had cancer in an advanced stage. Eleven patients underwent surgical resection, while three with distant metastasis were treated symptomatically. There was no postoperative mortality. Seven patients survived without evidence of recurrence, whereas four died of recurrence and three of gastric cancer progression. CONCLUSIONS: Renal transplant recipients are at increased risk of gastric adenocarcinoma, the most common malignancy in Korea. With curative surgery, favorable prognosis can be anticipated when the diagnosis is made at an early stage. Regular endoscopic examination for early diagnosis is recommended during the follow-up period after renal transplantation in a gastric cancer endemic area.

Adenocarcinoma↗