Metastases of pancreatic neuroendocrine tumor to the liver as extremely rare indication for liver transplantation in children. Case report and review of the literature.

Neuroendocrine tumors (NET) are extremely rare in children (0.75 cases per 100,000 children and adolescents a year) and the majority of these tumors are benign or present low grade of malignancy. According to the American registry Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, less than 2% of all neuroendocrine tumors in children occur in the pancreas, making it a rare site for these tumors. The majority of them are found in children over 10years of age, especially those with malignant potential. Treatment of NET consists of different methods: surgery, somatostatin analogues and chemotherapy. Radical surgical resection remains the standard of treatment; however, it is not always feasible because of distant metastases. The authors present a case report of pancreatic NET with multiple metastases to the liver. The patient was treated with pancreatic resection and liver transplantation for liver metastases. Prior to liver transplantation, the patient was treated with somatostatin analogues, sunitinib and chemotherapy. Management of liver metastases with liver transplantation is discussed.

Desmoid tumor of the pancreas: a case report.

INTRODUCTION: Desmoid tumor is a rare, benign, usually asymptomatic fibromatous lesion. The etiology is unknown and the diagnosis is based on histopathological examination. The treatment is complete resection of the tumor. Pancreatic desmoid tumor is extremely rare. In the literature there have been only 11 cases described, most of them as solid or solid-cystic masses. We report the case of a patient with an isolated cystic pancreatic desmoid tumor that is, to the best of our knowledge, the second reported case. CASE PRESENTATION: A 13-year old Caucasian boy presented with recurrent pain of two months' duration in the left hypochondrium of his abdomen. An ultrasound examination and computed tomography scan revealed the presence of a cystic mass located in his splenic hilum, tightly adjacent to the pancreatic tail. A splenic cyst was suspected. Operative findings showed a 10 x 10 cm cystic mass tightly connected to the pancreatic tail and left colonic flexure, adherent to the spleen, splenic vein and artery. Distal splenopancreatectomy with en bloc resection of the left colonic flexure was performed. Histological analysis confirmed that the resection was complete. The mass had infiltrated the pancreatic parenchyma. All tumor cells were positive for anti-beta-catenin staining characteristic for desmoid tumor. No abnormalities in the spleen and colon were found. CONCLUSIONS: Isolated sporadic pancreatic desmoid tumor with cyst formation is extremely rare and its diagnosis can be difficult, especially because of uncharacteristic symptoms and radiological findings, as in our patient. This case report should be of interest not only to surgeons, as the treatment of choice is radical resection, but also gastroenterologists, considering it is in close relation with familial adenomatous polyposis, and oncologists as the reason for differentiation with other pancreatic tumors.

Immunological factors and liver fibrosis in pediatric liver transplant recipients.

BACKGROUND: The aim of our study was to retrospectively assess any correlation between graft fibrosis and selected immunological factors in pediatric liver transplant recipients. MATERIAL AND METHODS: The study was performed on 33 patients after living related donor transplantation, divided into 2 groups depending on history of acute rejection episodes after transplantation. We assessed liver biopsies for presence of fibrosis, signs of antibody-mediated rejection, inflammatory infiltrations, and changes in bile ducts. We correlated these findings with assessment of anti-HLA antibodies. RESULTS: Among 14 patients with ACR, a history fibrosis was found in 8 patients (57%). In 19 patients without a history of ACR, fibrosis was found in 9 patients (47%). Anti-HLA antibodies were found in 47% of patients with fibrosis and in only 18.75% of patients without fibrosis. Among 3 patients with signs of antibody-mediated rejection, all had fibrosis in the graft 2 years after transplantation. We did not find any patient with chronic rejection or ductopenia. CONCLUSIONS: We suggest that there is a correlation between ACR and development of graft fibrosis present in liver grafts from recipients with normal liver biochemistry. Anti-HLA antibodies class II seems to be most important in development of fibrosis.

Antibody-mediated rejection in pediatric liver transplant recipients.

BACKGROUND: Antibody-mediated rejection (AMR), associated with the presence of C4d deposits, is well-defined in kidney transplantation but much less documented in liver transplantation (LTx). The aim of our study was to retrospectively analyze a group of pediatric liver transplant recipients who experienced episodes of acute rejection in the past, for the signs of AMR and its impact on liver histology. MATERIAL/METHODS: Our study population consisted of 18 patients after living related donor liver transplantation with a history of acute cellular rejection (1-5/patient). In all of them, actual liver function was good at almost 2-year median follow-up after transplantation. We reassessed all liver biopsies taken from these children between 5 days to 5.7 years after transplantation for signs of acute cellular rejection and antibody-mediated rejection. In all patients, anti-HLA antibodies were also assessed at least 2 years after transplantation (2.18-12.27 years, median 6.795 years). RESULTS: There were 27 episodes of acute rejection proved by liver biopsy. Signs of AMR were found in 6 of 18 patients (33.3%). In 5 of these patients, donor-specific (DSA) and non-specific anti-HLA antibodies were also identified. In the group of 12 patients with acute rejection without histochemical signs of AMR, anti-HLA antibodies were found in sera of only 5 of 12 patients after transplantation. CONCLUSIONS: Our study shows some correlation between C4d-positive reaction in liver biopsies with acute cellular rejection and presence of anti-HLA antibodies, particularly against HLA class II. We did not find any difference in the late graft function, which could be correlated with the presence of AMR. Further studies on larger groups of patients are necessary.

Treatment of undifferentiated embryonal sarcoma of the liver in children--single center experience.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) represents less than 5% of all malignant hepatic tumors in childhood. It is considered an aggressive neoplasm with an unfavorable prognosis. The aim of this paper is to present a single center experience in the treatment of children with UESL. MATERIALS AND METHODS: Ten children with UESL were treated between 1981 and 2012. Age at diagnosis ranged from 4 months to 17 years (median age, 6 years and 9 months). Surgery after neoadjuvant chemotherapy (CHT) was performed in 7 patients, and in 3 patients primary surgery was done. Adjuvant chemotherapy was administered in all 10 patients (CYVADIC, CAV, CAV/ETIF/IF+ADM, CDDP/PLADO). Right hemihepatectomy was performed in 1 patient, extended right hemihepatectomy in 6, and partial resection of the right lobe (segments V-VI, segment V) in 2 patients. One patient with unresectable tumor affecting both lobes was listed for liver transplantation (LTx). RESULTS: Follow-up from diagnosis ranged from 50 to 222 months (mean 138 months). Among 9 patients treated with partial liver resection, distant metastases/local recurrence was not observed in any, and disease-free survival in this group is 100% (9 patients alive). The patient that underwent liver transplantation died of multiorgan failure 4 months postoperatively. However, this patient was misdiagnosed as having hepatoblastoma (HBL) and received PLADO chemotherapy. The overall survival rate is 90%. CONCLUSION: Excellent results with long-term survival can be achieved in children with UESL with conventional therapy, including a combination of neoadjuvant and adjuvant chemotherapy and surgery, even in large extensively growing tumors.

Changing treatment and outcome of children with hepatoblastoma: analysis of a single center experience over the last 20 years.

BACKGROUND/PURPOSE: The aim of the study was to analyze changing management and survival of children with hepatoblastoma (HBL) treated in one center. MATERIALS AND METHODS: Over the last 20 years, 51 children with HBL were treated. Surgery was performed in 48 children (94.1%), conventional liver resection in 38 (of those, 2 received a rescue liver transplantation [LTx] for relapse), and total hepatectomy and primary LTx in 10 patients. The remaining 3 patients received only palliative treatment. Patient data were analyzed for survival with respect to PRETreatment EXTent of disease (PRETEXT), metastases, histopathology, conventional resection, and LTx. RESULTS: Survival of children with HBL treated with liver resection is 71% and 80% for primary LTx. Favorable prognostic factors for patient survival was tumor histology as epithelial-fetal subtype and mixed epithelial and mesenchymal type, without teratoid features, and good response to chemotherapy (necrosis, fibrosis). Unfavorable prognostic factors were small cells undifferentiated, transitional liver cell tumor, α-fetoprotein level above 1,000,000 IU/mL and below 100 IU/mL at diagnosis, lung metastases, and local recurrence after initial resection. Survival was related to PRETEXT stage. However, among patients with PRETEXT III and IV, LTx resulted in better survival. CONCLUSION: Liver transplantation is a good option for children with advanced HBL. Early referral of children with potentially unresectable tumors to centers where combined treatment (chemotherapy, surgery including LTx) is available is crucial.

The impact of donor-specific antibodies on graft outcome in pediatric renal transplantation from deceased donors.

BACKGROUND: Despite prospective crossmatching and modern immunosuppression, early acute rejection is still present in cadaveric renal transplantation. The purpose of this study was to evaluate the incidence of preformed anti-donor antibodies, detected by 2 solid-phase techniques, and to analyze their impact on early renal allograft outcome. MATERIAL/METHODS: Flow crossmatch detecting the presence of anti-donor IgG and IgM antibodies was performed in pre-transplant sera of 279 patients with negative cytotoxic crossmatch. Screening for IgG antibodies detected by bead-based multiplex technique was performed in sera of 69 patients from the FCXM group. The incidence of early biopsy-proven rejection and graft failure within 3 months after transplantation was analyzed. RESULTS: Anti-donor IgG antibodies were detected in 33 patients (11.8%) by flow crossmatch and in 10 patients by multiplex (14.5%). IgM antibodies were detected in 23 patients (8.2%). All multiplex-positive sera were also positive for IgG by flow crossmatch, but in 18 cases no antibodies were found by multiplex technique. Biopsy-proven acute rejection within 3 months after transplantation was observed in 16 patients, and 5 allografts were lost due to immunological reasons. Presence of IgG antibodies was found to have no effect on early outcome, while the presence of IgM antibodies was associated with significantly higher rejection rate and immune-related graft failure. CONCLUSIONS: Anti-donor IgG antibodies detected by bead-based and cell-based technique have no impact on biopsy-proven rejection rate or graft failure. Anti-donor IgM detected by flow crossmatch have significant impact on early transplantation outcome.

Hemodynamic failure as an indication to urgent liver transplantation in infants with giant hepatic hemangiomas or vascular malformations--report of four cases.

The aim of this study was to present acute hemodynamic failure as a rare indication for liver transplantation in neonates and infants with liver hemangiomatosis. We report four patients aged one to six months with giant liver hemangiomas, with huge arterio-venous shunting within these malformations. In three, many skin hemangiomas were found. All children developed right ventricular failure. In two, a trial of pharmacological reduction was attempted with corticosteroids and cyclophosphamide. In one patient, the arterio-venous fistulas were embolized without any improvement in hemodynamic status. Two children underwent rescue hepatic artery surgical ligation, which did not prevent heart and then multiorgan failure including liver failure. After unsuccessful conventional therapy, all infants were considered for urgent liver transplantation; in three cases, it was performed with a living-related donor, and in one case with a deceased donor. All patients are alive and well with the follow-up between nine and 37 months after transplantation. Liver transplantation should be considered as a rescue treatment in children with hepatic vascular malformations leading to hemodynamic insufficiency when conventional therapy is unsuccessful and multiorgan failure develops.

Local presence of cytomegalovirus and Candida species vs oral lesions in liver and kidney transplant recipients.

BACKGROUND: Anti-CMV prophylaxis is currently a routine management in patients after organ transplantation. One of the clinical symptoms of CMV infection may be lesions in the oral cavity.The aim of this study was to determine the relationship between CMV infection, occurrence of Candida species and presence of oral mucosal ulceration in transplant recipients. MATERIAL/METHODS: Twenty fi ve patients after kidney or liver transplantation (mean age 13 years +/-4 years), receiving immunosuppression (tacrolimus, cyclosporine or sirolimus), who presented minor and major recurrent aphtous stomatitis (RAS), atypical ulcerations or focal necrosis in the oral cavity were enrolled into the study. Mean duration of post-transplant follow-up was 4 years and 3 months (+/-3 years and 5 months). Clinical dental examination (Pl I, GI), mycological tests and blood tests for CMV infection (specific IgM antibodies and/or pp65 antygenemia) were performed in all patients. Eighteen specimens of oral mucosa were evaluated for CMV presence in situ. RESULTS: CMV infection was confirmed in 13 patients with oral mucosal ulceration (46.43%); which were accompanied by gingivitis (average GI=1.34); in two cases Candida albicans was identified. DNA of HCMV was found in-situ in 5.5% of all biopsies, and in 9% of biopsies of patients with clinical CMV infection; changes did not show the presence of Candida spp. CONCLUSIONS: There is a significant correlation between CMV infection and oral lesions; in some cases, CMV may be a direct cause.

Non-resectable hepatic tumors in children - role of liver transplantation.

BACKGROUND: There is a group of children with primary hepatic tumors which can not be resected by conventional partial liver resection. Total hepatectomy followed by liver transplantation may be the only solution in such cases. Authors reviewed own experience with the liver transplantation for unresectable tumors in children and assessed the possible indications and role of transplantation in these patients. MATERIAL AND METHODS: Liver transplantation was performed in 17 children with unresectable hepatic tumors out of total number of 350 children transplanted. Hepatocarcinoma was present in 8 children, hepatoblastoma in 6 and benign giant hemangioma in 3. There was no other option for the treatment which would lead to the oncological cure of children with malignant tumors. All patients with giant hemangiomas were infants transplanted urgently due to circulatory and then multiorgan failure. RESULTS: Survival within whole group is 75.5% (13 of 17 pts), 3 children died of malignant tumor recurrence, one of other causes. All 3 children with benign tumors are alive and well. Actual follow-up is from 3 months to 7 years. CONCLUSIONS: Liver transplantation should be considered as option in the treatment of all children with unresectable hepatic tumors. With the careful and individual patient selection significant chances for survival can be achieved in this group of patients which would otherwise not survive with the conventional treatment.

[Primary carcinoma of the thyroid growing in thyroglossal duct cyst: presentation of two cases]. / Pierwotny rak tarczycy w obrebie torbieli przewodu tarczowo-jezykowego: opis dwóch przypadków.

Thyroglossal duct remnants (TGDR), most often cysts, are the most common type of developmental abnormalities of the thyroid gland. In about 1 to 2% of TGDR neoplastic transformation occurs. Papillary carcinoma of the thyroid may be encountered in over 90% of such cases. Two cases of primary papillary carcinoma of the thyroid in TGDR in young girls are presented. The diagnostic and therapeutic problems are shared, and up-to-date management guidelines in similar cases are discussed.

[Bilateral papillary renal cell carcinoma in a patient post-renal transplantation]. / Obustronny rak "renal cell carcinoma" o typie brodawkowatym u pacjenta po transplantacji nerki.

Renal cancer accounts for about 2% of all cancers in general population. One of the risk factors is acquired cystic kidney disease developed in course of end- stage renal failure. About 2% of cases of renal cancer are associated with inherited syndromes. We present here the case of 18-year old boy with papillary bilateral renal cell carcinoma, which was found 3 years after renal transplantation, in the stage of graft failure, few days after graphtectomy, while looking for the reason of persistent fever.

[Preliminary results and complications of HCV treatment after liver transplantation]. / Wstepne wyniki i ocena powiklan leczenia zakazenia wirusem zapalenia watroby typu C (HCV) u pacjentów po transplantacji watroby.

UNLABELLED: The aim of study was to report the preliminary results and complications of HCV infection treatment after liver transplantation. MATERIAL: Six patients after liver transplantation (one after combine liver and kidney) had been qualified to treatment with pegylated interferon and ribavirin. RESULTS: In four patients the therapy was discontinued due to severe side effects (anaemia, cholestasis, sepsis, acute rejection). In two patients the normalization of biochemical parameters of liver function was achived after treatment. CONCLUSION: HCV treatement in solid organ recipients should be individualised.

Transitional liver cell tumors (TLCT) in older children and adolescents: a novel group of aggressive hepatic tumors expressing beta-catenin.

BACKGROUND: We encountered on seven malignant hepatocellular tumors developing in older children and adolescents. RESULTS: These tumors exhibit an unusual phenotype with respect to clinical presentation, histopathology, immunohistochemistry, and treatment response. As a working hypothesis, we suggest that these apparently novel, unusual, and aggressive tumors occurring in older children and adolescents may form a transition in the putative developmental pathway of hepatocarcinogenesis. CONCLUSION: We therefore propose the term, transitional liver cell tumors (TLCT), to denote these lesions.

Hemangioma of the liver in children: proliferating vascular tumor or congenital vascular malformation?

BACKGROUND: Hepatic vascular tumors (HVT) are the most common benign liver tumors present in infancy and childhood commonly associated with high output cardiac failure. Pediatric HVT usually are divided into infantile hemangioendothelioma (IHE), cavernous hemangioma (HC), and arteriovenous malformations (AVM). The aim of this study was to analyze clinical and histologic features of pediatric HVT in relation to treatment strategies. PROCEDURE: During last 12 years, 17 children have been treated because of HVT. The diagnosis of HVT was established in all on the basis of clinical and imaging data. A retrospective analysis of clinical records and histopathology divided 17 into: Group 1, neonates; and Group 2, infants and older children. RESULTS: Radiologic imaging revealed the vascular nature of the tumors in all patients. All nine from Group 1 were symptomatic from AVMs and seven were operated upon. Only one of eight children from Group 2 presented symptoms of AVM requiring surgery; four of five in this group had surgery because of the risk of malignancy. Within Group 1, a mixture of proliferating IHE with microscopic features of AVM was found in most. In three neonates with HVT immunologic and clinical features of cytomegalovirus (CMV) hepatitis were noted. In two Group 2 patients, pure HC was present and in another, the diagnosis of angiosarcoma was established after biopsy of a peritoneal metastasis. CONCLUSIONS: HVT in children demonstrate internal morphologic heterogeneity and an age-related behavior of the disease. We also confirm the proliferative nature of all hemangioendotheliomas (HEs) in children. Further studies on the tumorigenesis of these lesions are needed.