Long-Term Graft and Patient Survival After Re-Transplantation.

BACKGROUND Kidney transplant recipients have higher life expectancy but may require subsequent transplantations, raising ethical concerns regarding organ allocation. We assessed the safety of multiple kidney transplants through long-term follow-up. MATERIAL AND METHODS A retrospective cohort study was conducted at a single center, categorizing patients based on the number of kidney transplantations received. The primary outcome was the composite of death-censored graft failure and overall mortality. The secondary outcome was death-censored graft failure. RESULTS Between 2000 and 2019, our center performed 2152 kidney transplantations. Patients were divided into 3 groups: A (1 transplant; n=1850), B (2 transplants; n=285), and C (3 or more transplants; n=75). Group C patients were younger, had fewer comorbidities, and received more aggressive induction therapy. The primary outcomes, including death-censored graft loss and overall mortality, showed similar rates across groups (A: 21.3%, B: 25.2%, C: 21.7%, p=0.068). However, the secondary outcome of death-censored graft failure alone was significantly lower in group A compared to the other groups. No significant difference was observed between groups B and C (8% vs 16% and 13%, respectively, p=0.001, p=0.845). Multivariate analysis identified having a living donor as the strongest predictor of patient and graft survival in all study groups. CONCLUSIONS Graft and patient survival rates were similar between first and multiple transplant recipients. Multiple transplant recipients had lower death-censored graft failure risk compared to first transplant recipients. However, the risk did not differ among second and subsequent transplant recipients. Younger patients, especially those with a living donor, should be considered for repeat kidney transplantation.

The association between hydrochlorothiazide use and non-melanoma skin cancer in kidney transplant recipients.

Background: hydrochlorothiazide (HCTZ) diuretics were correlated with an increased risk of non-melanoma skin cancer (NMSC) and melanoma in the general population. Information is a scarce regarding this effect in kidney transplant recipients who are at increased risk of skin malignancies under immunosuppression. Methods: Single-center retrospective analysis of adult kidney transplant recipients between 1 January 2010 and 31 December 2015. The primary outcome of the study was the first diagnosis of skin cancer that was removed and pathologically analyzed. Exposure to thiazides was defined as HCTZ use daily for at least one year at a dose of 12.5 mg. Results: Among 520 kidney transplant recipients, 50 (9.4%) were treated with HCTZ. During a median follow-up of 9.8 years, 67 patients underwent surgical removal and pathological analysis of at least one skin cancer. Exposure to HCTZ during the 3 years following transplantation was associated with an increased risk of skin cancer (P = 0.004). In a multivariate model, there was a significant association between HCTZ exposure and NMSC (HR 2.54, 95%CI 1.26-5.15, P = 0.007). There was a higher rate of basal cell carcinoma with HCTZ exposure, according to both univariate and multivariate analyses (HR 2.61, 95%CI 1.06-6.43, P = 0.037) and (HR 3.03, 95%CI 1.22-7.55, P = 0.017, respectively). However, no significant association was observed between HCTZ exposure and squamous cell carcinoma. Conclusions: These findings suggest a benefit of increased frequency of dermatologist inspection in kidney transplant recipients receiving HCTZ especially in increased ultraviolet exposure area.

Bariatric Surgery in Severely Obese Kidney Donors Before Kidney Transplantation: A Retrospective Study.

BACKGROUND: Bariatric surgery (BS) is the optimal approach for sustained weight loss and may alter donation candidacy in potential donors with obesity. We evaluated the long-term effects of nephrectomy after BS on metabolic profile, including body mass index, serum lipids and diabetes, and kidney function of donors. METHODS: This was a single-center retrospective study. Live kidney donors who underwent BS before nephrectomy were matched for age, gender, and body mass index with patients who underwent BS alone and with donors who underwent nephrectomy alone. Estimated glomerular filtration rate (eGFR) was calculated according to Chronic Kidney Disease Epidemiology Collaboration and adjusted to individual body surface area to create absolute eGFR. RESULTS: Twenty-three patients who underwent BS before kidney donation were matched to 46 controls who underwent BS alone. At the last follow-up, the study group showed significantly worse lipid profile with low-density lipoprotein of 115 ± 25 mg/dL versus the control group with low-density lipoprotein of 99 ± 29 mg/dL ( P = 0.036) and mean total cholesterol of 191 ± 32 versus 174 ± 33 mg/dL ( P = 0.046). The second control group of matched nonobese kidney donors (n = 72) had similar serum creatinine, eGFR, and absolute eGFR as the study group before nephrectomy and 1 y after the procedure. At the end of follow-up, the study group had significantly higher absolute eGFR compared with the control group (86 ± 21 versus 76 ± 18 mL/min; P = 0.02) and similar serum creatinine and eGFR. CONCLUSIONS: BS before live kidney donation is a safe procedure that could increase the donor pool and improve their health in the long run. Donors should be encouraged to maintain their weight and avoid adverse lipid profile and hyperfiltration.

The Role of Early Sequential Biopsies in Delayed Renal Graft Function of Transplanted Kidney Is Reduced in Modern Immunosuppression Era.

BACKGROUND: Delayed graft function (DGF) immediately after kidney transplantation is considered a risk factor for acute rejection. According to clinical guidelines, a weekly allograft biopsy should be performed until DGF resolves. Based on clinical evidence, the first biopsy is considered appropriate. However, the recommendation for further biopsies is based on sparse evidence from era of earlier immunosuppression protocols, and the benefit of the second and further biopsies remains uncertain. The aim of this study was to reevaluate this policy. METHODS: The database of a transplant medical center was retrospectively reviewed for all patients who underwent kidney transplantation in 2011-2020. Those with DGF who performed two or more graft biopsies within the first 60 days after transplantation were identified. Clinical data were collected from the medical files. The rates of diagnosis of acute rejection at the second and subsequent biopsies were analyzed relative to the previous ones. RESULTS: Kidney transplantation was performed in 1,722 patients during the study period, of whom 225 (13.07%) underwent a total of 351 graft biopsies within 60 days after transplantation, mostly due to DGF. A second biopsy was performed in 32 patients (14.2%), and a third biopsy in 8, at weekly intervals. In 2 patients (6.25%), the diagnosis changed from the first biopsy (acute tubular necrosis or toxic damage) to acute rejection in the second biopsy. In both, the rejection was borderline. Third and fourth biopsies did not add information to the previous diagnosis. CONCLUSIONS: The common practice of performing sequential biopsies during a postoperative course of DGF seems to be of low benefit and should be considered on a case-by-case basis.

Gender specific survival rates after deceased donor liver transplantation: A retrospective cohort.

Background: According to the literature, there are sex allocation inequalities in liver transplantation (LT). Sex disparities in outcomes after LT have been debated. This study aimed to evaluate sex-specific outcomes after LT, specifically short-term mortality and long-term survival rates. Methods: A retrospective cohort of the entire LT series from to 2010-2019 in a single center in which the inclusion criteria were adults ≥18 YO age who underwent primary deceased donor LT. Mortality rate was evaluated within 30 days and 6 months. Survival rate was evaluated at 1,3 and 5 years of age. Results: A total of 240 primary and deceased donor LTs (153 men and 87 women) were included. Mean age 55.2Y men and 51.6Y women (p = 0.02). Hepatocellular carcinoma (HCC) was the direct indication in 32.7% of the men and only 17.4% of the women. The leading primary liver morbidities were viral hepatitis (B, C, and D) in 38.3% (N = 92) and nonalcoholic steatohepatitis (NASH) in 20.8% (N = 50) of patients. Thirty-day mortality was 14%, which was significantly higher in men (18%) than in women (8%). Survival rates after 5 years were 64.9% and 78.3%, respectively. Multivariate analysis through logistic regression that included age, direct indication, MELD, and primary liver morbidity revealed statistically significant female to male Odds-Ratio of 0.4 in 30 days, 6 m mortality and a statistically significant higher long-term survival. Conclusions: Our observations revealed better female outcomes, namely, lower short-term mortality and higher long-term survival. Given the consistency after stratification and given the multivariate analysis, this is unlikely to be attributable to confounders. Such findings suggesting consistently better female outcomes have not been previously reported; hence, multi center study is encouraged.

Long-term outcomes of Roux-en-Y gastric bypass or sleeve gastrectomy in patients with cirrhosis; before, during or after liver transplantation: A single center's experience.

BACKGROUND: The increasing prevalence of morbid obesity (MO) results in parallel growth of obesity-associated liver diseases necessitating liver transplantation (LT). OBJECTIVE: To examine the feasibility and safety of Roux-en-Y gastric bypass or sleeve gastrectomy in the setting of LT. METHODS: This retrospective chart review included the data on all the MO candidates before and after LT who underwent bariatric surgery (BS) in our institution between 04/2013-09/2016. The reported outcomes were weight change and early and late postoperative complications (mean follow-up: 43 ± 11.1 months). RESULTS: Eighteen MO peri-LT patients (10 females, 8 males, average age 48 years) were included in the study. Ten had cirrhosis (mean Model of End-stage Liver Disease [MELD] score of 12.5 ± 6.42), three underwent concurrent LT and BS (mean MELD score 23.7 ± 0.58), and five had LT (mean of 56 months from LT). The mean percentage of total and excess weight loss was 31% and 81%, respectively. Six of the eight patients with type 2 diabetes mellitus became normoglycemic after BS. Three patients sustained perioperative complications. Two cirrhotic patients died 1 and 4.5 years after BS with decompensation. CONCLUSIONS: Bariatric surgery appears to effectively address obesity in cirrhotic and LT patients. The surgical risk is higher than that of the regular BS population.

Flow-controlled fluoroscopic angiography for the assessment of vascular integrity in bioengineered kidneys.

Perfusion decellularization has been proposed as a promising method for generating nonimmunogenic organs from allogeneic or xenogeneic donors. Several imaging modalities have been used to assess vascular integrity in bioengineered organs with no consistency in the methodology used. Here, we studied the use of fluoroscopic angiography performed under controlled flow conditions for vascular integrity assessment in bioengineered kidneys. Porcine kidneys underwent ex vivo angiography before and after perfusion decellularization. Arterial and venous patencies were defined as visualization of contrast medium (CM) in distal capillaries and renal vein, respectively. Changes in vascular permeability were visualized and quantified. No differences in patency were detected in decellularized kidneys compared with native kidneys. However, focal parenchymal opacities and significant delay in CM clearance were detected in decellularized kidneys, indicating increased permeability. Biopsy-induced leakage was visualized in both groups, with digital subtraction angiography revealing minimal CM leakage earlier than nonsubtracted fluoroscopy. In summary, quantitative assessment of vascular permeability should be coupled with patency when studying the effect of perfusion decellularization on kidney vasculature. Flow-controlled angiography should be considered as the method of choice for vascular assessment in bioengineered kidneys. Adopting this methodology for organs premodified ex vivo under normothermic machine perfusion settings is also suggested.

Post-Liver Transplantation Anemia and Its Correlation with Mortality and Graft Failure.

BACKGROUND: In adults, post-liver transplantation anemia (PLTA) is common, but its characteristics and long-term influence on major outcomes have yet to be elucidated. AIM: We aimed to assess prevalence, characteristics, predictors, and outcomes of PLTA at 6 months (early PLTA) and at 2 years (late PLTA). METHODS: A single-center retrospective cohort study using prospectively collected data from liver transplantations in adults during January 2007-December 2015. PLTA impact on various long-term outcomes was assessed, including mortality, composites of mortality or graft failure, cardiovascular outcomes, and malignancy occurrences. RESULTS: Hundred and fifty liver transplanted individuals were included. There was a 79% prevalence of anemia pre-transplantation, whereas early and late PLTA were evident in 58% and 40% of patients, respectively. Pre-transplantation anemia was associated with development of early PLTA which was associated with late PLTA. In a multivariate analysis, early PLTA was significantly associated with mortality or graft failure at a follow-up of 3 years (odds ratio 3.838, 95% CI 1.114-13.226). Late PLTA was not significantly associated with worse long-term outcomes. CONCLUSIONS: Early and late PLTA are prevalent among liver transplanted patients. Early PLTA is associated with long-term mortality or graft failure.

Bariatric Surgery Is Efficacious and Improves Access to Transplantation for Morbidly Obese Renal Transplant Candidates.

BACKGROUND: The surgical risk of morbidly obese patients is high and even higher for kidney transplant candidates. A BMI > 35-40 kg/m2 is often a contraindication for that surgery. The safety, feasibility, and outcome of bariatric surgery for those patients are inconclusive. METHODS: We conducted a retrospective chart review of prospectively collected data on morbidly obese renal transplant candidates who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in our institution between January 2009 and September 2017. The reported outcome included body weight and graft status after a mean follow-up of 47 months (range 0.5-5 years). RESULTS: Twenty-four patients (8 females, 16 males, average age 54 years, average preoperative BMI 41 kg/m2 [range 35-51]) underwent LSG (n = 17) or LRYGB (n = 7). Sixteen of them (67%) proceeded to kidney transplantation. Of the 8 pre-transplant and post-bariatric surgery patients, 5 are on the waitlist, and 2 patients died (one of staple line leakage, and one from sepsis unrelated to the bariatric surgery). The average time from bariatric surgery to transplantation was 1.5 years (range 1 month to 4.3 years). The average pre-transplantation BMI was 28 kg/m2 (range 19-36). The mean percentage of excess weight loss was 66% (n = 21), and the total percentage of weight loss was 29% (n = 21). Comorbidities (type 2 diabetes, hypertension, and dyslipidemia) improved significantly following both surgical approaches. CONCLUSIONS: LSG and LRYGB appear to effectively address obesity issues before kidney transplantation and improve surgical access. Morbidly obese transplant candidates would benefit from prior bariatric surgery.

Survival benefit in bariatric surgery kidney recipients may be mediated through effects on kidney graft function and improvement of co-morbidities: A case-control study.

BACKGROUND: Data on the benefits of bariatric surgery for morbid obesity among kidney transplant recipients are scarce. OBJECTIVE: To examine the effect of bariatric surgery on graft function and survival and on obesity-related co-morbidities. SETTING: University hospital. METHODS: This case-control study used retrospectively collected data of all kidney recipients who underwent bariatric surgery in our institution between November 2011 and August 2016 (n = 30, 11 females). Nonbariatric operated kidney recipients matched for age, sex, and time elapsed since transplantation served as controls (n = 50, 23 females). Main outcomes were renal function, graft loss events, mortality, and obesity-related co-morbidities. RESULTS: The mean follow-up duration was 2.4 ± 1.3 years for both groups. At final follow-up, there was an increase in estimated glomerular filtration rates for the bariatric surgery group, and a decrease for the controls (13.4 ± 19.9 and -3.9 ± 15.8 mL/min/1.73 m2, respectively, P < .001). The chronic kidney disease classification improved in 9 bariatric surgery group patients and in 6 controls (P = .1). Two patients in the bariatric surgery group and 6 controls died. Total death or graft function loss during the follow-up was 6.7% and 16.7%, respectively (P = .3). The total numbers of co-morbidities and medications were lower in the bariatric surgery patients (-.7 and -2, respectively) and higher in the controls (+.3 and +1.1; P < .001) at study closure. CONCLUSIONS: There was an improvement in renal function, graft survival, and obesity-related co-morbidities among kidney transplant recipients who underwent bariatric surgery compared with those who did not. These findings support bariatric surgery in this population and warrant prospective studies.

Bariatric surgery in solid organ transplant patients: Long-term follow-up results of outcome, safety, and effect on immunosuppression.

The surgical risk of transplanted patients is high, and the modified gastrointestinal anatomy after bariatric surgery (BS) may lead to pharmacokinetic alterations in the absorption of immunosuppressive drugs. Data on outcomes of BS and the safety and feasibility of maintaining immunosuppression and graft safety among solid organ transplanted patients are scarce. In the current study, weight loss, improvement in comorbidities, and changes in dosage and trough levels of immunosuppression drugs before and after BS were analyzed for all transplanted patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in our institution between November 2011 and January 2017. Thirty-four patients (13 females, 21 males, average age 53 years) were included in the study. A successful weight loss (>50% excess weight loss in 28 of them [82%]) was recorded at the last follow-up. Comorbidities improved significantly. Immunosuppressive stability increased from 39% to 47% among all patients. The tacrolimus blood trough levels declined slightly, but remained within therapeutic range. These data suggest that LSG and LRYGB ensure good immunosuppressive maintenance together with significant weight loss and improvement in comorbidities without serious graft rejection or dysfunction. The surgical risk is higher than in the regular BS population.

Simultaneous Liver Transplantation and Sleeve Gastrectomy: Prohibitive Combination or a Necessity?

Previously, many morbidly obese (MO) patients were denied liver transplantation (LT) because of the higher operative risk. However, nowadays, 5 and 10 years graft survival is the rule, and patients whose lives can be prolonged with LT are dying of obesity-related comorbidities. Recent experience suggests that weight reduction in MO liver transplant recipients would improve their long-term survival. The bariatric surgery before LT is contraindicated for patients with decompensated cirrhosis, while post-transplant intervention is associated with increased technical difficulty. We present our experience with three patients who underwent simultaneous liver transplantation and sleeve gastrectomy. After a median 13 months follow-up, all patients are alive, having normal allograft function and significant weight loss. Combined liver transplantation with simultaneous sleeve gastrectomy appears technically feasible and relatively safe in selected patients.

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy in peritoneal carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis is an advanced form of cancer with poor prognosis that in the past was treated mainly palliatively. Today, the definitive approach to peritoneal surface malignancy involves peritonectomy, visceral resection and perioperative intra-abdominal hyperthermic chemotherapy. The anticipated results range from at least palliative to as far as intent to cure. Proper patient selection is mandatory. OBJECTIVES: To determine whether cytoreductive surgery and intraperitoneal hyperthermic chemotherapy can extend survival, and with minor complications only, in patients with peritoneal carcinomatosis. METHODS: Twenty-two IPHP procedures were performed in 17 patients with peritoneal carcinomatosis in our institution between 1998 and 2007: 6 had pseudomyxoma peritonei, 5 had colorectal carcinoma, 3 had ovarian cancer and 3 had mesotheliomas. All patients underwent cytoreductive surgery, leaving only residual metastasis < 1 cm in size. Intraperitoneal chemotherapy was administered through four large catheters (2F) using a closed system of two pumps, a heat exchanger and two filters. After the patient's abdominal temperature reached 41 degrees C, 30-60 mg mitomycin C was circulated intraperitoneally for 1 hour. RESULTS: The patients had a variety of anastomoses. None demonstrated anastomotic leak and none experienced major complications. Six patients had minor complications (pleural effusion, leukopenia, fever, prolonged paralytic ileus, sepsis), two of which may be attributed to chemotherapy toxicity (leukopenia). There was no perioperative mortality. Some patients have survived more than 5 years. CONCLUSIONS: IPHP is a safe treatment modality for patients with peritoneal carcinomatosis. It has an acceptable complications rate and ensures a marked improvement in survival and in the quality of life in selected patients.

Bauhin's ileocecal valve syndrome-a rare cause for small-bowel obstruction: report of a case.

Benign ileocecal valve hypertrophy is a rare cause for intestinal obstruction. We describe a 51-year-old female with clinical and imaging presentation of chronic small-bowel obstruction. The patient was operated on, and a limited thickening of the ileocecal bowel wall causing intestinal obstruction was found. A right hemicolectomy was performed. On microscopic examination, severe fibrosis with hypertrophied nerves was found without any additional findings of malignancy or inflammation. Review of the relevant literature is presented.

Photodynamic therapy for Bowen's disease and squamous cell carcinoma of the skin.

BACKGROUND: Photodynamic therapy involves the activation by visible light of a previously administered photosensitizing agent in order to cause tumor necrosis. Skin tumors can be treated with topical photosensitizers and thus avoiding systemic side effects. In this study we evaluate the immediate and long-term effects of photodynamic therapy (PDT), using aminolevulinic acid (ALA) as a photosensitizer and a non-laser light source, on Bowen's disease (intra-epithelial squamous cell carcinoma) and on frank squamous cell carcinoma (SCC) of the skin. METHODS: ALA in cream form (20%) was topically applied on biopsy-proven Bowen's disease or SCC of the skin. The lesions were covered with occlusive and light-shielding dressing. Sixteen hours later, they were submitted to a 10-min light session using Versa-Light™, a non-laser light source (spectral output of 580-720nm and 1250-1600nm, 100J/cm(2)). The initial evaluation was done 21 days post-treatment and every 3m thereafter. Patients that did not respond to treatment after two to three sessions were referred to surgery. RESULTS: Forty Bowen's disease lesions (24 patients) and 43 SCC lesions (18 patients) underwent treatment. Median follow-up was 21±8m. No patient had any remarkable side effects. Thirty-four Bowen's disease (85%) lesions completely responded as did 32 SCC lesions (74%). CONCLUSIONS: Our findings showed that PDT is highly effective in treating Bowen's disease and SCC lesions and can be used as a first treatment modality in so far as its use does not preclude the subsequent surgery recommended for the small percentage of failures.