Combined liver-kidney transplantation for primary hyperoxaluria type I in children: Single Center Experience.

Primary hyperoxalurias are rare inborn errors of metabolism with deficiency of hepatic enzymes that lead to excessive urinary oxalate excretion and overproduction of oxalate which is deposited in various organs. Hyperoxaluria results in serious morbid-ity, end stage kidney disease (ESKD), and mortality if left untreated. Combined liver kidney transplantation (CLKT) is recognized as a management of ESKD for children with hyperoxaluria type 1 (PH1). This study aimed to report outcome of CLKT in a pediatric cohort of PH1 patients, through retrospective analysis of data of 8 children (2 girls and 6 boys) who presented by PH1 to Wadi El Nil Pediatric Living Related Liver Transplant Unit during 2001-2017. Mean age at transplant was 8.2 ± 4 years. Only three of the children underwent confirmatory genotyping. Three patients died prior to surgery on waiting list. The first attempt at CLKT was consecutive, and despite initial successful liver transplant, the girl died of biliary peritonitis prior to scheduled renal transplant. Of the four who underwent simultaneous CLKT, only two survived and are well, one with insignificant complications, and other suffered from abdominal Burkitt lymphoma managed by excision and resection anastomosis, four cycles of rituximab, cyclophosphamide, vincristine, and prednisone. The other two died, one due to uncontrollable bleeding within 36 hours of procedure, while the other died awaiting renal transplant after loss of renal graft to recurrent renal oxalosis 6 months post-transplant. PH1 with ESKD is a rare disease; simultaneous CLKT offers good quality of life for afflicted children. Graft shortage and renal graft loss to oxalosis challenge the outcome.

Therapeutic superiority of combined propranolol with short steroids course over propranolol monotherapy in infantile hemangioma.

UNLABELLED: Infantile hemangiomas are the most common benign childhood tumor that may have functional and/or cosmetic complications. We aimed to compare the clinical efficacy of propranolol alone and propranolol primed with systemic corticosteroids on the outcome of infantile hemangioma. A prospective randomized study included 40 infants aged less than 9 months with cutaneous hemangiomas. Patients were randomly assigned into two groups: group A were given oral prednisolone for the initial 2 weeks combined with oral propranolol, while group B were given oral propranolol alone for 6 months. The median age of the studied patients was 4.5 months (ranged 4 weeks-8 months). Sequential determination of the dimensions of the hemangiomas based on direct measurement and photographic analysis were performed. A significant reduction in the size of the lesions was found in group A in the 2-, 4-, and 8-week evaluation compared to group B (p < 0.001) with no statistical difference in the ultimate 6 month response (p = 0.134). Multiple logistic regression showed that early treatment before 6 months of age (OR 9.82, p = 0.007) and combined treatment with propranolol and prednisolone (OR 10.71, p = 0.006) were the predictors of best response. CONCLUSION: Combining propranolol with corticosteroids gives a faster response and should be considered in treating life- or function-threatening hemangiomas.

Bone demineralization in a cohort of Egyptian pediatric liver transplant recipients: Single center pilot study.

Liver transplantation (LT) is the definitive treatment of end-stage liver disease. The long-term survival following LT spurred more interest in improving the quality of life of patients. This was a cohort study that included 23 pediatric liver transplant recipients who underwent LT due to hereditary or metabolic liver diseases. Bone health assessment was performed at their last follow up clinically (anthropometric measures), biochemically and radiologically (Dual Energy X-ray Absorptiometry [DEXA] scans). Poor bone health was defined as z-score <-1. Mean age at LT was 5.77 years (standard deviation [SD] 3.64) and 43% were males. Biliary atresia was the most common cause of end stage liver disease (35%). Mean age at follow up was 14 years (SD 5.48) and mean follow up was 8 years (SD 4.12 years). Eleven patients (48%) had poor bone health (osteopenia 22% and osteoporosis 26%). On univariate analysis, being on steroids at last follow up (odds ratio [OR] 13.2, 95% confidence interval [CI] 1.23-140.67, P = .03), weight at last follow up (OR 0.45, 95% CI 0.20-0.99, P = .04), platelets at last follow up (OR 0.98, 95% CI 0.96-s0.99, P = .02), hemoglobin at last follow up (OR 0.33, 95% CI 0.12-0.89, P = .03) were significantly associated with poor bone health. None of the variables were significant on multivariate analysis. At most recent follow up, 48% of patients demonstrated poor bone health by DEXA scans. More studies are required to evaluate predictors of poor bone health after LT in children.

Intra-abdominal testis: histological alterations and significance of biopsy.

PURPOSE: Intra-abdominal testes represent only 5% of undescended testes. Review of the literature reveals that few data exist on the histological analysis of intra-abdominal testes. We studied histological alterations in intra-abdominal testes in relation to patient age at orchiopexy. MATERIALS AND METHODS: A total of 57 boys underwent laparoscopy for impalpable undescended testes between October 2002 and June 2005. Testicular biopsies were taken from intra-abdominal testes, fixed in 3% glutaraldehyde, embedded in Epon, sectioned at 1 micron thickness and stained with toluidine blue. Histomorphometric analysis was performed by light microscopy. Effect of age at operation on histological evaluation of abdominal testes was also studied. RESULTS: Testicular biopsies from 29 patients with intra-abdominal testes showed the histological alterations of decreased mean diameter of seminiferous tubules, germinal cell depletion (55%) and presence of microliths (6.9%). CONCLUSIONS: As age at orchiopexy increases, deviation from the norm is more evident and absence of germ cells on biopsy becomes more pronounced, reaching a rate of 93% after age 3 years. Further studies on orchiopexy with or without biopsy in the first few months of life would likely improve our understanding and treatment of cryptorchidism.

Biliary complications including single-donor mortality: experience of 207 adult-to-adult living donor liver transplantations with right liver grafts.

BACKGROUND: After right lobe donation, biliary complication is the main cause of morbidity. Mortality after right lobe donation has been estimated to be less than 0.5%. PATIENTS AND METHODS: Between November 2001 and December 2008, 207 adult-to-adult living donor liver transplantations (ALDLT) were undertaken using right lobe grafts. Donors included 173 men and 34 women with a mean age of 28.4 +/- 5.2 years. RESULTS: Siblings comprised 144 (69.6%) cases whereas unrelated donors comprised 63 (30.4%) with a mean body mass index (BMI) of 25.2 +/- 2.4. Single and multiple right hepatic ducts (RHD) were present in 82 (39.6%) and 125 (60.3%) donors, respectively. Mean operative time was 360 +/- 50 min with an estimated blood loss of 950 +/- 450 ml and returned cell-saver amount of 450 +/- 334 ml. Mean donor remnant liver volume was 33.5 +/- 3.2%. Mean intensive care unit (ICU) stay was 3 +/- 0.7 days and mean hospital stay was 14 +/- 3.5 days. Modified Clavien classifications were used to stratify all donor biliary complications The overall biliary complications occurred in 27 cases (13.0%). After modified Clavien classification, biliary complications were graded as grade I (n= 10), grade II (n= 2), grade III (n= 14) and grade V (n= 1). Grade I and II (n= 12) biliary complications were successfully managed conservatively. Grade III cases were treated using ultrasound-guided aspiration (USGA), endoscopic retrograde cholangiography (ERCP) and surgery in 10, 2 and 2 donors, respectively. Single donor mortality (Grade V) (0.4%) occurred after uncontrolled biliary leakage with peritonitis that necessitated exploration followed by ERCP with stent insertion but the donor died on day 43 as a result of ongoing sepsis. CONCLUSION: Although the majority of biliary complications are minor and can be managed conservatively, uncontrolled biliary leakage is a serious morbidity that should be avoided as it could lead to mortality.

Colonic replacement in cases of esophageal atresia.

Replacement of the esophagus in children is still a challenging problem; one of the major indications is failed esophageal atresia repair or long-gap ones. The colon is one of the best alternatives for replacement; long-term follow up has shown satisfactory results. In cases of complicated repair receiving frequent dilation and multiple operations, colon could be an alternative choice for these children to achieve normal swallowing.

The safety of modern hydroxyethyl starch in living donor liver transplantation: a comparison with human albumin.

BACKGROUND: Intravascular volume replacement therapy is an important issue in the perioperative management of liver transplantation. There is paucity of data on the safety of hydroxyethyl starch (HES) in patients undergoing liver transplantation. We evaluated the safety of a new HES 130/0.4 in the perioperative management of liver transplantation, with a special emphasis on renal function. METHODS: Forty patients undergoing living donor liver transplantation were prospectively randomized into two groups. Patients in the ALB group (n = 20) received 5% human albumin. Patients in the HES group (n = 20) received third generation HES (6% HES 130/0.4). Total colloid administration was limited to 50 mL x kg(-1) x d(-1). The volume was given to maintain pulmonary artery occlusion pressure or central venous pressure between 5 and 7 mm Hg. If additional fluids were required, balanced crystalloid solution was used. Anesthetic and surgical techniques were standardized. Serum creatinine and cystatin C plasma levels were measured from arterial blood samples after induction of anesthesia, at the end of surgery, and on the first 4 postoperative days. RESULTS: All 40 enrolled patients completed the study. Demographic and intraoperative variables were comparable in both groups. Postoperatively, the mean +/- sd volume was 6229 +/- 1140 mL and 4636 +/- 1153 mL in HES and ALB groups, respectively (P = 0.003). There was significantly greater [corrected] net cumulative fluid balance in the HES [corrected] group 3047 +/- 2000 [corrected] mL compared with the ALB group 1100 +/- 900 [corrected] mL, P = 0.029. Serum creatinine, creatinine clearance, and cystatin C plasma levels showed no significant differences between the two groups. One patient in each group developed acute renal failure requiring renal replacement therapy. CONCLUSION: The use of HES 130/0.4 as an alternative to human albumin resulted in equivalent renal outcome after liver transplantation.

Enhancement of dissolution amount and in vivo bioavailability of itraconazole by complexation with beta-cyclodextrin using supercritical carbon dioxide.

The main objective of this study was to improve the inclusion formation between itraconazole and beta-cyclodextrin and thus enhance dissolution amount and bioavailability characteristics of itraconazole. Inclusion complexes between itraconazole and beta-cyclodextrin were prepared using simple physical mixing, conventional coprecipitation method, and supercritical carbon dioxide (SC CO(2)). Effects of process variables (temperature, pressure) and drug:cyclodextrin ratio on inclusion yield and thermal behavior of the solid complexes prepared by SC CO(2) were studied and compared to those obtained by physical mixing and coprecipitation methods. In addition, dissolution amounts of the products obtained by different methods were measured in gastric fluid. Finally, pharmacokinetic studies of the inclusion complexes were conducted in male Wistar rats to assess the bioavailability of the prepared complexes. Results showed that temperature, pressure and itraconazole:beta-cyclodextrin ratio had significant effects on the inclusion yield of the complex prepared by SC CO(2) method. Higher inclusion yields were obtained in the SC CO(2) method as compared to physical mixing and coprecipitation methods. In vivo drug pharmacokinetic studies showed that the itraconazole-beta-cyclodextrin product prepared using SC CO(2) gave higher bioavailability of itraconazole (in blood, liver and kidney of male Wistar rats) as compared to the products obtained by physical mixing or coprecipitation methods.

Pulmonary hypertension and cardiac hypertrophy in children recipients of orthotopic living related liver transplantation.

Surgical stress, liberation of cytokines associated with re-perfusion injury, and long standing use of immune suppressive medications in children recipients of orthotopic living related liver transplantation (OLRLT) pose cardiovascular risk. Reported cardiovascular adverse effects vary from left ventricular wall thickening, hypertrophic cardiomyopathy to resting ECG abnormalities, asymptomatic ST depression following increased heart rate and ventricular arrhythmias. Twenty-five consecutive children recipients of OLRLT were assessed by conventional 2-D, M-mode echocardiography and Doppler. The mean age ± SD at transplantation and at enrollment in study was 6.3 ± 4.5 and 13.5 ± 5.6 years respectively. All children were on immunosuppressive medications, with tacrolimus being constant among all. Long-term post-transplant echocardiography revealed statistically significant interventricular septal hypertrophy among all (mean thickness 0.89 ± 0.16 cm), (P = 0.0001) in comparison to reference range for age, 24 had pulmonary hypertension (mean mPAP 36.43 ± 5.60 mm Hg, P = 0.0001), and early diastolic dysfunction with a mean Tei index of 0.40 ± 0.10. However cardiac function was generally preserved. Children recipients of OLRLT have cardiac structural and functional abnormalities that can be asymptomatic. Pulmonary hypertension, increased cardiac mass, de novo aortic stenosis and diastolic heart failure were among abnormalities encountered in the studied population. Echocardiography is indispensible in follow-up of children recipients of OLRLT.

Oxidative stress mediates drug-induced hepatotoxicity in rats: a possible role of DNA fragmentation.

Sodium diethyldithiocarbamate, diclofenac and ketoconazol are three important chemotherapeutic agents that are commonly associated with hepatotoxicity. This study was undertaken to provide a better understanding of the mechanism through which these drugs induce hepatotoxicity. Some of the possible mechanisms underlying such modulation were investigated. The hepatotoxic activity of sodium diethyldithiocarbamate (800 mg kg(-1)); diclofenac (200 mg kg(-1)) and ketoconazol (100 mg kg(-1)) were investigated in vivo through the assessment of liver functions, lipid peroxidation and histopathological examination. It was found that all drugs have induced severe hepatic damage as evidenced by the elevation serum aminotransferase activities and confirmed by histological changes of liver. In addition, the drug-induced hepatotoxicity was also associated with massive liver DNA fragmentation and an increase in lipid peroxidation. These results strongly suggest a positive correlation between hepatotoxicity and DNA fragmentation. Moreover, this study also implicates calcium as a potential mediator of the drug-induced oxidative stress associated with hepatotoxicity.

Evaluation of Lipofilling Safety in Elderly Patients with Breast Cancer.

BACKGROUND: Lipofilling is widely used in breast reconstruction after mastectomy with reconstruction or breast conserving surgery in patients with breast cancer. The aim of this study is focused on complications associated with lipofilling in elderly breast cancer patients with breast defects after breast conserving surgery or reconstruction. METHODS: A total of 137 patients older than 60 years who underwent 153 lipofilling procedures were included. All patients had undergone breast lipofilling using Coleman's technique. Estimated breast defect volume, lipofilling volume, and complications after lipofilling were obtained for analysis. RESULTS: Most patients (67%) had only 1 lipofilling procedure. The median lipofilling volume to breast defect volume ratio was 1.5. No severe complications were found after treatment. Liponecrosis was detected in 10 of 153 breasts (7%) or 9 of 137 patients within 2 weeks after lipofilling and required surgical drainage in 2. No local recurrences were noted. CONCLUSIONS: The incidence of liponecrosis after lipofilling in elderly patients was relatively high, requiring surgical drainage in some cases. As a rough guide, the lipofilling volume should not exceed 1.5 times the defect volume, and close postoperative follow-up within the first 2 weeks is suggested for these patients.

Technique for Minimizing Donor-site Morbidity after Pedicled TRAM-Flap Breast Reconstruction: Outcomes by a Single Surgeon's Experience.

BACKGROUND: Breast reconstruction with pedicled transverse rectus abdominis myocutaneous (TRAM) flap can result in significant abdominal wall donor-site morbidity. We present our technique of transversely dividing the anterior fascia and rectus abdominis combined with reinforcement above the arcuate line for closure of the anterior abdominal wall defect to prevent contour deformities performed by a single senior surgeon and compare these results with those of our prior series. METHODS: We described our new technique of closure of the abdominal wall defect and retrospectively performed the comparison between the results of pedicled TRAM flaps using the new closure technique and those of 420 pedicled TRAM flaps from our 2003 publication in terms of abdominal bulging and hernia. RESULTS: Sixty-seven pedicled TRAM flaps in 65 patients were compared with 420 pedicled TRAM flaps of the 2003 series. The new technique was associated with 5 partial TRAM flap necroses (8%). There was no total flap loss with the new technique. The median follow-up period was 13 months (range, 4-36 months). There were no instances of abdominal hernia and bulge during follow-up in the new series. Compared with the previous 2003 series, the new technique was superior in terms of occurrence of abdominal wall hernia or bulging. CONCLUSIONS: We are still performing pedicled TRAM flap for autologous breast reconstruction. Using the technique of transversely dividing the anterior fascia and rectus abdominis combined with reinforcement above the arcuate line can reduce the occurrence of abdominal bulging and hernia.

Non-surgical treatment of early breast cancer: techniques on the way.

Trials are still on the way to evaluate different non-surgical techniques to treat early breast cancer with achieving maximum oncological control and aesthetic outcome. Also these techniques can help old patients to bypass surgical and radiation complications and facilitate the treatment of early breast cancer with minimum side effects.

Oncoplastic technique in breast conservative surgery for locally advanced breast cancer.

Locally advanced breast cancer (LABC) should be taken into decision making when planning breast conservative surgery, but this procedure should be done on the principle of oncologic safety in order to achieve negative surgical margin and maintain aesthetic result. This procedure should be offered as the choice of treatment in selected patients.

Nipple sparing mastectomy: does breast morphological factor related to necrotic complications?

BACKGROUND: Nipple sparing mastectomy (NSM) can be performed for prophylactic mastectomy and the treatment of selected breast cancer with oncologic safety. The risk of skin and nipple necrosis is a frequent complication of NSM procedure, and it is usually related to surgical technique. However, the role of the breast morphology should be also investigated. METHOD: We prospectively performed an analysis of 124 NSM from September 2012 to January 2013 at the European Institute of Oncology, Milan, Italy, focusing on necrotic complications. We analyzed the association between the risks of skin necrosis and the breast morphology of the patients. RESULTS: Among 124 NSM in 113 patients, NSM procedures were associated with necrosis in 22 mastectomies (17.7%) among which included partial necrosis of nipple-areolar complex (NAC) in 15 of 124 NSM (12.1%) and total necrosis in 4 cases (3.5%). The NAC was removed in 5 NSM cases (4%). The volume of breast removed was the only significant factor increasing the risk of skin necrosis. The degree of ptosis was not significantly related to the necrosis risk. CONCLUSIONS: Large glandular specimen increases the risk of NAC necrosis. The degree of ptosis and the distance between the sternal notch and the NAC have no significant impact on necrotic complications in NSM. To reduce the necrotic complications in large breast after NSM, reconstruction should better be performed with autologous flap or slow skin expansion using the expander technique.

Immediate breast reconstruction: does the pathology affect the reconstruction?

Immediate breast reconstruction is related to many factors like type of mastectomy, desire of the patient but pathology is not included which should be encountered in decision making in immediate breast reconstruction.

Lipofilling in breast cancer surgery.

Recently, lipofilling is being performed either as a part of oncoplastic technique or alone by itself for correction of defects and asymmetry after oncologic breast cancer surgery. Its efficacy, safety and technical procedures are varying among institutions and individual surgeon's experiences. We provide a literature review and view point focus on this novel technique which emphasize on the application on breast cancer reconstruction.

Topical mitomycin C application is effective in management of localized caustic esophageal stricture: a double-blinded, randomized, placebo-controlled trial.

BACKGROUND: Frequent sessions of endoscopic dilatation are usually required in the management of benign esophageal strictures, especially caustic induced ones. Topical mitomycin C (MMC) has been recently used in the management of resistant strictures. This study evaluated the efficacy of MMC application in prevention of stricture recurrence after endoscopic dilatation. PATIENTS AND METHODS: This double-blind, randomized, placebo-controlled trial included forty patients with caustic esophageal strictures dating from January 2008 to October 2010. Patients were randomized into 2 groups to undergo endoscopic dilatation with application of either MMC versus placebo on stricture site. Regular follow up and re-evaluation were done after 6 months of management. The number of dilatation sessions needed for resolution of dysphagia in each group was our primary outcome. RESULTS: During the specified follow up period, 80 % of strictures in the MMC group got completely resolved compared to only 35% in the placebo group. The mean number of dilatation sessions needed in the MMC group was n = 3.85 ± 2.08 compared to n = 6.9 ± 2.12 in the placebo group which was statistically significant (p < 0.001). CONCLUSION: Mitomycin C application significantly reduced the number of dilatation sessions needed to alleviate dysphagia in patients with caustic esophageal strictures.

Free nipple graft technique to correct nipple and areola malposition after breast procedures.

SUMMARY: Secondary correction of nipple areola complex (NAC) malposition represents a major concern after breast reconstructive procedures. It is frequently requested by patients complaining about asymmetric areolas impairing the whole reconstructive procedure and asking for improved cosmetic outcomes. Several methods have been described to achieve a good symmetry between the 2 areolas, either natural or reconstructed. We describe our correction technique with free NAC graft. A total of 16 patients were treated with free NAC grafts between April 2010 and April 2013 at the European Institute of Oncology, Milan, Italy. This series focused on the surgical technique and its postoperative outcomes. Three cases of partial graft loss (18%) were observed in the postoperative period. No total NAC necrosis occurred. No infection was observed. All the complications were managed with a conservative treatment, not requiring any further surgery. NAC malposition following breast reconstructive procedures can be corrected using the technique of free NAC graft with reliable and satisfactory results.