H. Karakayali

Etiologic agents of diarrhea in solid organ recipients

Abstract: After transplantation, diarrhea may be caused by infectious agents, drug‐specific effects, metabolic conditions, or mechanical complications of surgery. Determining the cause helps to determine whether to initiate antimicrobial therapy and the duration of treatment. In this study we aimed to determine the causes of diarrhea in kidney or liver recipients. Fifty‐two diarrhea episodes among 43 solid organ recipients were evaluated. The cause of diarrhea was detected in 43 patients (82.6%). Infectious etiologies accounted for 33 out of the 43 episodes (76.7%) in which a specific cause was determined: Giardia lamblia in 9, Cryptosporidium parvum in 7, cytomegalovirus (CMV) in 6, Clostridium difficile in 3, Campylobacter jejuni in 2, Shigella sonnei in 2, Salmonella enteritidis in 1, rotavirus in 1, Entamoeba histolytica in 1, and Blastocystis hominis in 1. Non‐infectious etiologies were found for 10 episodes (23.3%): mycophenolate mofetil‐associated diarrhea in 5, antibiotic‐associated diarrhea in 2, colchicine‐associated diarrhea in 2, and laxative drug‐associated in 1. Non‐infectious etiologies seem to be relatively common causes of diarrhea among transplant recipients. Therapy was adjusted in 5 patients because of mycophenolate mofetil‐associated diarrhea. CMV and C. parvum, which are seldom seen in the normal population, were frequent causes of diarrhea in this group. Evaluating the transplant recipients for non‐infectious causes of diarrhea is important in prompt diagnosis and treatment.

Clinicopathological significance of PTEN loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: is PTEN loss predictor of local recurrence?

BACKGROUND PTEN is a tumor-suppressor gene located on chromosome 10. Deficient PTEN expression leads to activation of the phosphoinositide 3-kinase (PI3K)/Akt (pAkt) signaling pathway, which may contribute to multiple human cancers. The relation between PTEN expression and Akt activation is still unclear in colorectal cancers and adenomatous polyps. Moreover, PTEN and pAkt expression in relation to demographic, tumoral, and outcome variables remains to be elucidated. METHODS PTEN and pAkt expression were evaluated in 76 primary colorectal cancers and 25 adenomatous colorectal polyp tissues using immunohistochemical staining on paraffin-embedded sections. PTEN and pAkt expression were compared with clinicopathologic features of colorectal cancers. The relationship between PTEN and pAkt expression was also investigated. RESULTS In colorectal cancers, pAkt expression was found to be significantly higher than polyps (P = .007). On the other hand, PTEN expression was significantly lower in polyps (P <.0001). In colorectal cancer patients, PTEN expression showed a negative correlation with young age, female sex, and left-sided (distal) tumors. On multivariate analysis, low PTEN expression (PTEN loss) was noted as an independent parameter for local recurrence (P = .024). There was significant association between pAkt expression and stage (P = .008), and preoperative serum carcinoembryonic antigen (CEA) levels (P = .017) in colorectal cancers. A negative correlation between PTEN and pAkt expression was found in colon cancer patients (P = .010), whereas no significiant association was found in adenomatous polyps (P = .403). No correlation of PTEN expression or pAkt expression was observed in Kaplan-Meier survival statistics and multivariate analyses for disease-free and overall survival. CONCLUSIONS The current study suggests that the PTEN loss-PI3K/pAkt pathway may play an important role in sporadic colon carcinogenesis and that reduced PTEN expression may predict relapse in colorectal cancer patients.

Is Routine Preoperative Ultrasonographic Mapping for Arteriovenous Fistula Creation Necessary in Patients with Favorable Physical Examination Findings? Results of a Randomized Controlled Trial

IntroductionPreoperative ultrasonographic mapping (PUSM) is widely used for arteriovenous fistula creation in end-stage renal disease patients, and some authors even advocate that it be used routinely. To date, however, there are no prospective randomized data to support this suggestion.MethodsThis prospective, randomized, controlled study compared PUSM and physical examination in relation to short-term outcome after AVF creation. Data sets from 70 hemodialysis patients who were deemed eligible for AVF surgery—according to specific physical examination (PE) criteria for vessel anatomy—were analyzed. The patients were randomly divided into two groups. In the PE group, no other investigation was performed, and the patient underwent AVF creation. The other patients (M group) underwent PUSM, and the AVF was created according to the mapping results. Early AVF success was defined as clinical detection of thrill (immediately and on postoperative day 1). Ultrasonographic parameters were recorded on the first postoperative day and at 1 and 6 months postoperatively. The need for intervention and intervention-free AVF survival and cumulative AVF survival were also noted.ResultsThe PE and M groups showed similar rates of early AVF success: immediate thrill, PE 24/35 (68.6%) vs. M 26/33 (78.8%), P = 0.340; postoperative day 1, PE 20/34 (58.8%) vs. M 24/32 (75%), P = 0.164. The groups’ results for ultrasonographic parameters of AVF function were also similar on postoperative day 1 and at 1 month after surgery. The groups had similar intervention-free AVF survival (P = 0.770) and cumulative AVF survival as well (P = 0.916). After an average follow-up of 217.7 ± 239.7 days, the two groups also had similar proportions of patent AVFs: 23/35 (65.7%) vs. 23/35 (65.7%) for PE vs. M, respectively; P = 1.0).ConclusionsThe results indicate that PUSM offers no advantage over PE with regard to AVF function in patients with favorable forearm anatomy. The authors do not advocate routine use of PUSM in patients with favorable PE findings scheduled for forearm AVF creation.

Analysis of Vascular Complications After Renal Transplantation

PURPOSE Despite medical and surgical advances, vascular complications remain common after renal transplant, occurring among 3%-15% of patients. These complications may compromise graft function. This study sought to evaluate the frequency and management of vascular complications after renal transplant. MATERIALS AND METHODS We retrospectively analyzed the 1843 transplantations performed at 2 centers by our team since November 1975. The 1349 male and 494 female patients had an overall mean age of 31.5±11.2 years; (range, 3-66). Grafts were obtained from a living-related donor in 1406 (76.29%) or a deceased donor in the remaining 437 (23.71%). The mean donor age was 40.7±13.7 years (range, 2-76). Of 1843 transplants, multiple vascular anastomoses were performed in 155 cases (8.4%), including 130 involving renal arteries and 25 renal veins. RESULTS Forty-seven vascular complications (2.55%) were observed in 43 procedures (2.33%), most frequently renal artery stenosis (n=14). It was followed by allograft renal artery kinking (n=7), renal vein kinking (n=7), renal artery thrombosis (n=5), renal vein laceration (n=4), renal artery laceration (n=3), renal vein thrombosis (n=2), renal artery disruption (n=2), renal and iliac vein obstructions owing to pressure from a lymphocele (n=1), renal artery and vein obstruction owing to pressure from a hematoma (n=1), or an arteriovenous fistula after percutaneous graft biopsy (n=1). Fifteen of these 47 complications were treated by interventional radiologic procedures. CONCLUSION The vascular complication rates in our patients were somewhat lower than those reported in the literature. A thorough understanding of how complications impair allograft function and survival is essential for adequate treatment. Interventional radiology is invaluable in the postoperative management of transplant-related complications.

Rituximab for post-transplant recurrences of FSGS.

Abstract:  A 14‐yr‐old boy whose primary kidney disease was FSGS developed severe recurrence of proteinuria immediately after a second living‐related kidney transplant. Despite pre‐ and post‐operative PP and immunosuppressive treatment consisting of steroids, CycA, daclizumab, and MMF, daily protein excretion and serum creatinine increased. We therefore administered rituximab on the fourth day of transplantation. He received four weekly doses of rituximab (375 mg/m2/dose), which resulted in a rapid clearing of circulating CD19‐positive B cells, and remission of proteinuria was achieved six wk after the first rituximab treatment. Graft function was excellent six months after transplantation with proteinuria of 8 mg/m2/h. We conclude that rituximab may be an effective treatment for post‐transplant recurrence of FSGS.

Evaluation of Erectile Function in Renal Transplant Recipients

RECTILE dysfunction describes the inability to achieve and maintain penile erection sufficient for coitus. Renal insufficiency is a chronic disease during which erectile function deteriorates, however, the etiology of this condition in such patients is multifactorial, involving organic and nonorganic (psychogenic) factors. 1 The condition may result from neuroendocrine disturbance, uremia, hypoxia, and atherosclerosis. 2 Neuroendocrine disturbance is often reversed by renal transplantation, but not by dialysis. 3 Psychological factors may also cause erectile dysfunction in dialysis patients, since approximately one fourth of these individuals are depressed at any given time. 4 Patients often regain potency after transplantation but in some cases, especially second transplantations, erectile function is adversely affected by interference with arterial blood flow. In this study, we evaluated the effect of renal transplantation on erectile function. PATIENTS AND METHODS Information on erectile function was collected by means of a questionnaire given to 65 men who were renal transplant recipients. The patients ranged in age from 20 to 57 years (mean 42.5 years). A second transplantation had been performed in four cases (6%). Posttransplantation follow-up ranged from 2 to 168 months (mean 72 months). A detailed medical history was taken and complete blood count, urinalysis, and a biochemical and endocrinologic blood analysis were routinely performed for all patients. A papaverine test, penile Doppler ultrasonography, cavernosometry, cavernosography, and pudendal angiography were done where indicated. For patients who had no erectile dysfunction before or after renal transplantation, the questionnaire and routine tests completed the evaluation. This group was considered to have experienced no change in erectile function due to renal transplantation. Similarly, no further tests were performed on patients who were afflicted with erectile dysfunction prior to renal transplantation but regained sexual function following transplantation. These patients were defined as the group with improved sexual function. On the other hand, patients with deteriorated erectile function after renal transplantation were evaluated in detail. All underwent a papaverine test involving intracavernous injection of 50 mg of papaverine and observation of response after 30 minutes. The group which experienced full erection after papaverine treatment (papaverine responders) was considered to have nonorganic (psychogenic) erectile dysfunction. Patients who did not respond to papaverine were further evaluated by penile Doppler ultrasonography for vasculogenic impotence. Papaverine-stimulated penile Doppler ultrasound was performed using a 7.5-MHz linear probe. Peak systolic velocities in the cavernous arteries were measured bilaterally. A peak systolic velocity of ,25 cm/s was considered as arterial insufficiency. Patients with arterial insufficiency underwent pudendal angiography, while those with normal penile Doppler ultrasound findings underwent dynamic infusion cavernosometry and cavernosography to assess for suspected veno-occlusive dysfunction. RESULTS Thirty-two patients (49.2%) experienced no alteration in erectile function before or after renal transplantation. Twelve patients (18.4%) said they regained erectile function after renal transplantation. Twenty-one patients (32.3%) with normal erectile function prior to transplantation during the hemodialysis period reported erectile dysfunction after the transplantation, constituting the group which was evaluated further. Seven of these patients were papaverine responders (nonorganic impotence) and benefited from antiserotoninergic treatment. All seven men received 150 mg/d trazodone initially, however, two patients who reported severe side effects with this drug were switched to sertraline at a dose of 50 mg/d. All patients in this group achieved erections sufficient for coitus within 3 months. In three patients, deterioration of erectile function was associated with hyperprolactinemia accompanied by a low testosterone level. A papaverine test was not performed in these cases. Oral testosterone replacement resulted in improved sexual function. Eleven of 21 patients who reported a deterioration in erectile function after transplantation did not respond to papaverine. These individuals were considered to have vasculogenic impotence. According to penile Doppler ultrasound, nine of these men had arterial insufficiency, while two had normal peak systolic velocities in their cavernous arteries, indicating no arterial insufficiency. These two patients underwent cavernosometry and cavernosography, which confirmed veno-occlusive dysfunction. They were treated with deep dorsal vein embolization using n-butyl cyanoacrylate, and regained satisfactory erections within 3 months, at which time control cavernosometry was normal.

MR Cholangiopancreatography with T2-Weighted Prospective Acquisition Correction Turbo Spin-Echo Sequence of the Biliary Anatomy of Potential Living Liver Transplant Donors

OBJECTIVE The objective of our study was to evaluate the ability of a respiratory navigator-triggered T2-weighted turbo spin-echo (TSE) sequence with a prospective acquisition correction (PACE) technique for MR cholangiopancreatography (MRCP) to depict the biliary anatomy of living donor liver transplantation (LDLT) donors. SUBJECTS AND METHODS Forty potential LDLT donors who ranged in age from 19 to 54 years were prospectively evaluated with preoperative MRCP. MRCP was performed with a 1.5-T magnetic field using T2-weighted PACE TSE sequence. MRCP source data sets were processed with maximum-intensity-projection (MIP) and shaded surface display (SSD) algorithms. Findings were compared with intraoperative cholangiography. Biliary anatomy was classified according to the classification proposed by Huang and colleagues. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRCP for the detection of aberrant biliary anatomy were calculated. RESULTS Intraoperative cholangiography and biliary exploration revealed that 27 donor candidates (67.5%) had conventional and 13 (32.5%) had aberrant biliary anatomy. Two donors (5%) had type B biliary anatomy; eight donors (20%), type C; two donors (5%), type D; and one donor (2.5%), unclassified. The sensitivity of MRCP source data sets in differentiating aberrant biliary anatomies from nonaberrant ones was 100%, the specificity was 88.9%, and the accuracy was 92.5%. PPV and NPV were 81.3% and 100%, respectively. The sensitivity of MIP images in differentiating aberrant biliary anatomies was 100%, the specificity was 88.9%, and the accuracy was 92.5%. PPV and NPV were 81.3% and 100%, respectively. The sensitivity, specificity, accuracy, PPV, and NPV of the SSD images in detecting aberrant biliary anatomies were 100%, 77.8%, 85%, 68.4%, and 100%, respectively. CONCLUSION Preoperative MRCP using a respiratory navigator-triggered T2-weighted TSE sequence with a PACE technique accurately depicts the biliary anatomy in LDLT donors and may guide intraoperative management of the biliary tract.

Hepatocellular carcinoma in Wilson's disease: A rare association in childhood

Abstract:  Wilsons disease is a hereditary disorder of copper metabolism that results in the accumulation of copper in the body, primarily in the liver, brain, and cornea. Hepatocellular carcinoma, in contrast to other causes of cirrhosis, is seldom associated with Wilsons disease. We present a 12‐yr‐old boy with Wilsons disease in whom hepatocellular carcinoma was incidentally diagnosed in the pathologic specimen examined after liver transplantation.

Endovascular stent placement in patients with hepatic artery stenoses or thromboses after liver transplant.

Hepatic artery stenosis or thrombosis following liver transplant is a potentially life-threatening complication. Successful liver transplant depends on uncompromised hepatic arterial inflow. Early diagnosis and treatment of complications prolong graft survival. Interventional radiologic techniques are frequently used to treat hepatic artery complications. Twenty patients with hepatic artery stenoses (n = 11) or thromboses (n = 9) were included in this study. Eighteen of the 20 patients were successfully treated by stent placement. In 9 patients, early endovascular interventions were performed 1 to 7 days after surgery. Two patients were operated owing to the effects of dissection and bleeding from the hepatic artery. Repeat endovascular interventions were performed 10 times in 6 patients. Follow-up ranged from 5 months to 4.5 years. Nine patients with patent hepatic arteries died during follow-up owing to reasons unrelated to the hepatic artery interventions. In 3 patients, the stents became occluded at 3, 5, and 9 months after surgery but no clinical symptoms were present.

Delayed graft function: predictive factors and impact on outcome in living-related kidney transplantations

The aim of this study was to determine the incidence and possible causes of delayed graft function (DGF) and its impact on outcome in living-related kidney transplantations. We analyzed 158 consecutive living-related kidney transplant recipients. DGF is described as the failure of serum creatinine to fall below pretransplant levels within 1 week of the operation, regardless of urine output. Of the 158 patients studied, 14 (8.8%) fit this criterion. Donor and recipient factors such as age, gender, body weight, recipient/donor weight ratio, HLA match, cyclosporine level, blood group, and anastomosis time of patients with DGF were compared to those of patients without DGF. Apart from donor gender, body weight, and recipient/donor body weight ratio, these parameters were similar in the two groups. In the DGF group the majority of the donors were female (11/14), whereas this was not the case in the controls (64/144; p < 0.02). Mean donor weight in patients experiencing DGF (59.6 +/- 9.2 kg) was significantly lower than in those without DGF (67.8 +/- 10.4 kg; p < 0.05). The mean recipient/donor weight ratio for the DGF group (1.26) was significantly higher than that of the control group (1.03, p < 0.02). The 5-year graft survival rates for patients with and without DGF were 74% and 77%, respectively (NS). On the other hand, the 5-year graft survival rate for patients with DGF complicated by an acute rejection episode (n = 6, 61%) was significantly lower than that of control group patients who experienced acute rejection (n = 43, 74%; p < 0.02). These results indicate that female donor gender and higher recipient/donor weight ratio are major predictive factors in the development of DGF following living-related kidney transplantation. Although DGF alone did not affect the outcome, long-term graft survival was significantly reduced when DGF was associated with acute rejection episodes.