Importance of Pancreatic Enzyme Replacement Therapy after Surgery of Cancer of the Esophagus or the Esophagogastric Junction.

After surgical treatment of cancer of the esophagus or the esophagogastric junction we observed steatorrhea, which is so far seldom reported. We analyzed all patients treated in our rehabilitation clinic between 2011 and 2014 and focused on the impact of surgery on digestion of fat. Reported steatorrhea was anamnestic, no pancreatic function test was made. Here we show the results from 51 patients. Twenty-three (45%) of the patients reported steatorrhea. Assuming decreased pancreatic function pancreatic enzyme replacement therapy (PERT) was started or modified during the rehabilitation stay (in the following called STEA+). These patients were compared with the patients without steatorrhea and without PERT (STEA-). Maximum weight loss between surgery and rehabilitation start was 18 kg in STEA+ patient and 15.3 kg in STEA- patients. STEA+ patients gained more weight under PERT during the rehabilitation phase (3 wk) than STEA- patients without PERT (+1.0 kg vs. -0.3 kg, P = 0.032). We report for the first time, that patients after cancer related esophageal surgery show anamnestic signs of exocrine pancreas insufficiency and need PERT to gain body weight.

Central venous port systems as an integral part of chemotherapy.

BACKGROUND: Port systems are easy to implant on an in- or outpatient basis and provide reliable, long-lasting central venous access. They are used mainly for cancer patients. METHODS: This article is based on a selective literature review, the guidelines of the German Society for Nutrition Medicine and of the European Society for Clinical Nutrition and Metabolism, and the recommendations of the German Society for Pediatric Oncology and Hematology. RESULTS: In modern oncology, central venous port systems are increasingly replacing short-term and permanently tunneled central venous catheters. They are indicated for patients who need long-term intravenous treatment involving, e.g., the repeated administration of chemotherapeutic drugs, parenteral nutrition, transfusions, infusions, injections, and/or blood sample collection. Port systems can markedly alleviate the burden of intravenous therapy and thereby improve these patients' quality of life. The planning, preparation, and performance of port system implantation require meticulous attention to detail. The rate of implantation-associated complications is less than 2% in experienced hands; overall complication rates have been reported from 4.3% to as high as 46%. The proper postoperative use and care of the port system are of decisive importance to the outcome. Reported infection rates during port system use range from 0.8% to 7.5% in current clinical studies. CONCLUSION: The treatment, follow-up care, and rehabilitation of cancer patients are interdisciplinary tasks. Optimal treatment and complication avoidance require a collaborative effort of all of the involved specialists-not just the physician implanting the port system, but also the oncologists, nutritionists, visiting nurses, and other home health care providers. Continuing medical education, too, plays a role in improving outcomes.

Long-term results after liver transplantation.

Liver transplantation (OLT) has become a successful surgical therapy for terminal liver failure. We here report about long-term results of OLT in a single center over a period of 15 years. Between 1988 and 2002, 1365 adult OLTs were performed. Mean follow-up was 103 +/- 56 months. Main indications for OLT were viral-induced cirrhosis (27.1%), alcoholic liver disease (21%), tumors (15.7%) and cholestatic liver disease (14.6%). Retransplantation was necessary in 120 (9.6%) patients because of initial nonfunction (26.9%), recurrence of underlying disease (20.2%), acute and chronic rejection (16.8%) or thrombosis of the hepatic artery (16.8%). 275 patients (22.1%) died. Causes of death included recurrence of disease (32.1%), infections (21.8%), de novo malignancies (13.5%) and cardiovascular disease (11.6%). Patient survival after OLT was 91.4%, 82.5%, 74.7% and 68.2% after 1, 5, 10 and 15 years, and graft survival was 85.8%, 75.3%, 67.3% and 61.7% after 1, 5, 10 and 15 years, respectively. Patient survival after retransplantation was 81.6%, 68.8% and 57.1% and 48.0% after 1, 5, 10 and 15 years. This analysis reveals excellent long-term results after OLT achieved in a single center.

The place of liver transplantation in the treatment of hepatic epitheloid hemangioendothelioma: report of the European liver transplant registry.

BACKGROUND: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up. MATERIAL AND METHODS: Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%) patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)] and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%) patients had extrahepatic disease localization before or at the time of LT. Follow-up was complete for all patients with a median of 92.5 (range, 7-369) from moment of diagnosis and a median of 78.5 (range, 1-245) from the moment of LT. RESULTS: HEHE was bilobar in 96% of patients; 86% of patients had more than 15 nodules in the liver specimen. Early (<3 months) and late (>3 months) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients developed disease recurrence after a median time of 49 months (range, 6-98). Nine (15.3%) patients died of recurrent disease and 5 are surviving with recurrent disease. One-, 5-, and 10- year patient survival rates from moment of transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs. 95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN) invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%, 78%, and 67% in node negative patients) and extrahepatic disease localization (n = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70% in case of absence of extrahepatic disease) did not significantly influence patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10-year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and 10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%, 82%, and 64%. Disease-free survival is not significantly influenced by pre-LT treatment, LN status, extrahepatic disease localization, and vascular invasion. CONCLUSIONS: The results of the largest reported transplant series in the treatment of HEHE are excellent. Preexisting extrahepatic disease localization as well as LN involvement are not contraindications to LT. Microvascular or combined macro-microvascular invasion significantly influence survival after LT. LT therefore should be offered as a valid therapy earlier in the disease course of these, frequently young, patients. Recurrent (allograft) disease should be treated aggressively as good long-term survivals can be obtained. Long-term prospective follow-up multicenter studies as well as the evaluation of antiangiogenic drugs are necessary to further optimize the treatment of this rare vascular hepatic disorder.

Antineoplastic activity of 2-methoxyestradiol in human pancreatic and gastric cancer cells with different multidrug-resistant phenotypes.

BACKGROUND AND AIM: Chemoresistance often leads to loss of the last treatment option for cancer. 2-Methoxyestradiol (2-ME2) has been shown to inhibit tumor growth. The aim was to examine the efficacy of 2-ME2 on multidrug-resistant human cells from pancreatic and gastric cancer. METHODS: We investigated the impact of 2-ME2 on multidrug-resistant cells derived from human pancreatic and gastric cancer cells that were positive or negative for the MDR1-gene. RESULTS: In pancreatic cancer cells, growth inhibition was 57% in parental, 72% in MDR1-negative and 87% in MDR1-positive cells after 1 micromol/L 2-ME2. In gastric cancer cells we found a growth inhibition of 75% in parental, 82% in MDR1-positive and 95% in MDR1-negative cells. Strong induction of apoptosis was induced after a low dose of 2-ME2. No significant difference in the amount of apoptotic cells was observed between parental and multidrug-resistant cells of both tumor types. The number of apoptotic cells after 2-ME2 ranged from 7.5% in parental gastric cancer cells to 20.1% in MDR1-negative gastric cancer cells. CONCLUSION: 2-ME2 may therefore have clinical application for chemoresistant cancer.

Lower-extremity lymphedema following neck dissection--an uncommon complication after cervical ligation of the thoracic duct.

Thoracic duct injuries and chylous fistula are well-known complications of neck dissection, occurring in 1-2% of cases. Management of these injuries can be conservative or operative. Conservative treatment consists of fat restricted diet or total parenteral nutrition reducing the volume of chyle production. Operative management includes exploration of the neck or if necessary open thoracotomy to ligate the thoracic duct. Following cervical thoracic duct ligation only few complications like chylothorax or chylous ascites are described in the literature. To the best authors knowledge, this is the first report in the english literature describing lower-extremity lymphedema following cervical thoracic duct ligation.

Trends and experiences in liver retransplantation over 15 years.

Compared to primary liver transplantation (LT), the inferior results in the outcome of liver retransplantation (re-LT) continue to be a major challenge. The purpose of this study was to analyze changes in and outcomes of re-LT over a period of 15 years at the Charité Virchow Clinic. Between 1989 and 2003, we performed 1,619 LTs and 157 re-LTs (9.7%) in 1,462 patients. A total of 119 retransplants (50 females, 69 males) were analyzed after consideration of exclusion criteria: recipient age <16 years, second re-LT, primary LT as split-liver or living-related LT, or combination with renal transplantation or Whipple operation. All patients received a whole-size organ. Mean follow-up was 62 months (6 days to 187 months). The main indications for re-LT were initial nonfunction (26.9%), recurrence of viral-induced hepatitis (20.2%), or acute and chronic rejection or thrombosis of the hepatic artery (both 16.8%). The main causes of death were bacterial infections (26.0%) as well as bleeding complications or recurrence of disease (both 16.0%) within the first postoperative month. Overall, 50 out of 119 patients (42%) died after re-LT, 26 patients within the first 3 months and 38 within 1 year. Overall patient survival was 89.9% after 1 month, 78.2% after 1 year, and 67.1% after 5 years. In conclusion, our study showed good clinical results after re-LT. Apart from the changing indications for re-LT with an increasing amount of initial organ failure and hepatic artery thrombosis, the analysis also showed a decreasing amount of complications such as rejection, ischemic type biliary lesions, and recurrence of the disease with unchanged outcome over a period of 15 years.

Long-term survival and predictors of relapse after orthotopic liver transplantation for alcoholic liver disease.

The relevance of sobriety for outcome after orthotopic liver transplantation (OLT) for alcoholic liver disease (ALD) is still discussed controversially. We conducted a retrospective analysis of 300 patients transplanted for ALD with regard to recurrent alcohol consumption, risk factors for drinking after OLT, and long-term survival. The 300 patients underwent OLT for ALD between 1989 and 2002. Median follow-up was 89 months. Incidence and severity of drinking, survival rates, and causes of death were assessed. Age, gender, duration of pretransplant sobriety, social support, presence of children, and the results of psychosomatic evaluation were analyzed for their impact on recurrent alcohol consumption after OLT. Drinking of various degrees was observed in 19% of ALD patients after OLT. Pretransplant sobriety of less than 6 months, absence of companion in life, presence of young children, and a predicted poor psychosomatic prognosis were associated with an increased risk of recurrent alcohol consumption, whereas age and gender were not independent risk factors. Survival rates of patients who resumed abusive drinking were significantly lower than survival rates of abstinent patients or patients with minor lapses. Recurrent alcoholic liver disease accounted for the vast majority of deaths among patients who resumed abusive drinking after OLT, whereas malignant tumors, infections, and cardiovascular disease were the most common causes of death among abstinent patients. In conclusion, abusive drinking after OLT is associated with poor long-term survival. Analysis of risk factors may help to identify patients with a high risk for recurrent alcohol abuse after OLT.

Liver transplantation for hereditary hemorrhagic telangiectasia: Report of the European liver transplant registry.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a rare disease characterized by the presence of arteriovenous malformations. Hepatic involvement can lead to life-threatening conditions. MATERIAL AND METHODS: Forty patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation in the treatment of the hepatic disease form. Indications for transplantation were classified according to Garcia-Tsao: cardiac failure (14 patients), biliary necrosis causing hepatic failure (12 patients), severe portal hypertension (5 patients), cardiac failure and biliary necrosis (6 patients), cardiac failure and portal hypertension (2 patients), and cardiac failure associated with biliary necrosis and portal hypertension (1 patient). Eighteen (81%) of 22 patients had pulmonary artery hypertension. Twelve (30%) patients had pretransplant hepatic interventions. Follow-up was complete for all patients with a mean of 69 months (range, 0-230 months). RESULTS: One-, 5- and 10-year actuarial patient and graft survival rates are 82.5%. Six of the 7 pretransplant procedures performed on the hepatic artery were severely complicated. Cardiovascular function documented in 24 patients improved in 18 patients and remained stable in 5 patients; 1 patient died perioperatively of acute heart failure. Twenty-four (60%) patients had post-transplant complications, all but one occurring within the first 4 posttransplant months. Seven (17.5%) patients died perioperatively, 6 of them due to bleeding and 1 due to cardiac failure; 1 (2.5%) patient died late due to chronic rejection. There were 2 possible recurrences. Quality of life markedly improved in all 32 surviving patients. CONCLUSION: The results of the largest reported transplant series in the treatment of hepatic-based HHT are excellent. Elimination of hepatobiliary sepsis and reversal of cardiopulmonary changes dramatically improve quality of life of the recipients. LT should be proposed earlier in the course of symptomatic hepatic HHT presenting with life-threatening conditions. Palliative interventions, especially on the hepatic artery, should be avoided in view of their high (infectious) complication rate.

Long-term results of mycophenolate mofetil as part of immunosuppressive induction therapy after liver transplantation.

BACKGROUND: The addition of mycophenolate mofetil (MMF) to the induction protocol resulted in a lower incidence of rejection episodes. However, the question whether MMF should be administered in combination with tacrolimus or cyclosporine has not been answered yet. In our study, we report on the long-term results of triple induction therapy after orthotopic liver transplantation (OLT), consisting of MMF and low-dose corticosteroids, in combination with either tacrolimus or cyclosporine. METHODS: Between March 1996 and April 1997, 120 consecutive patients, who underwent OLT at our institution, were enrolled in this study. Of these patients, 80 received triple induction therapy consisting of cyclosporine and MMF (40) or tacrolimus and MMF (40), in combination with low-dose corticosteroids, whereas the remaining 40 patients served as 'MMF-free' control group receiving dual induction therapy with tacrolimus and corticosteroids. Besides the eight-yr follow-up of patient and graft survival, clinical data were also reviewed for episodes of rejection and infection. Additionally, the early post-operative pharmacokinetics of mycophenolic acid (MPA, immunological active metabolite of MMF) were evaluated. RESULTS: Long-term results provided higher patient and graft survival after tacrolimus/MMF-based induction therapy than after cyclosporine/MMF-based induction therapy. However, the tacrolimus-based control protocol yielded similar results and, therefore, no significantly superior effect was observed when MMF was added. The same observation was made for incidence of rejection and infection episodes. AUC and C(max) of MPA increased in combination with tacrolimus compared with cyclosporine. CONCLUSIONS: Although pharmacological synergy between tacrolimus and MMF was observed, MMF showed no significant beneficial effects in the immunosuppressive induction protocol, neither in combination with tacrolimus nor with cyclosporine.

Indications of mycophenolate mofetil in liver transplantation.

Mycophenolate mofetil (MMF) is approved for prophylaxis of acute rejection after kidney, heart, and liver transplantation as well as for pediatric patients after kidney transplantation. MMF, a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH), blocks de novo purine synthesis which leads to an effective inhibition of proliferation selectively in T and B lymphocytes, smooth muscle cells, and fibroblasts. MMF shows additional effects with inhibition of the expression of activating and adhesion molecules on the surface of lymphocytes. The beneficial safety profile with distinct side effects compared to calcineurin inhibitors (CNI) enable efficacious combination with ciclosporin or tacrolimus as de novo therapy after liver transplantation. Furthermore, recent studies show the possibility to reduce CNI induced toxicities by adding MMF to primary immunosuppression. MMF is also used to enable early steroid withdrawal after liver transplantation. MMF can increase efficacy of immunosuppressive therapy and thereby support the treatment of steroid resistant acute rejections, chronic rejections and chronic graft dysfunction.

ALK-1 mutations in liver transplanted patients with hereditary hemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominantly inherited disorder characterized by cutaneous and mucosal telangiectasias, epistaxis and arteriovenous malformations in lung, liver, central nervous system, and gastrointestinal tract. Mutations in the genes for endoglin (ENG) and for activin A receptor type II-like kinase 1 (ALK-1) have been identified to be associated with HHT. Intrahepatic manifestation in HHT might lead to the requirement of liver transplantation. We report here on 6 liver transplanted patients and 2 who were scheduled for liver transplantation due to intrahepatic HHT, in whom both genes were sequenced. Mutation analysis revealed in all patients the presence of mutations in ALK-1. In conclusion, these results are of possible prognostic value concerning the need of liver transplantation in HHT patients.

Mycophenolatemofetil for immunosuppression after liver transplantation: a follow-up study of 191 patients.

BACKGROUND: Mycophenolatemofetil (MMF) combined with calcineurin inhibitors (CNIs) as immunosuppression after orthotopic liver transplantation (OLT) is still under discussion. We retrospectively investigated the immunosuppressive potency of MMF for treatment of steroid-resistant acute rejection (AR) or chronic rejection (CR), chronic graft dysfunction, and CNI-induced toxicity in patients after OLT. METHODS: Between 1988 and 2001 we performed 1386 OLTs in 1258 patients. Since 1995, 191 patients have received MMF after OLT for steroid-resistant AR or CR, chronic graft dysfunction (115 patients), and CNI-induced toxicity (76 patients). The mean follow-up time was 56 months. RESULTS: Of 47 patients with steroid-resistant AR, 12 had been treated with OKT3, without resolving the rejection. Overall, bilirubin and transaminases decreased significantly within 2 weeks after the addition of MMF, and liver function normalized in 38 patients. Five of eight patients with CR demonstrated stable liver function after a follow-up of 55+/-8 months; 52 of 60 patients with chronic graft dysfunction improved within 3 months; and 46 of 59 patients with CNI-induced nephrotoxicity improved after MMF treatment and a reduction of CNIs (with a significant decrease in serum creatinine within 2 weeks and an increase of creatinine clearance within 3 months). Clinical symptoms improved in 10 of 12 patients with neurotoxicity and four of five patients with hepatotoxicity. Side effects of MMF, such as gastrointestinal disorders or bone marrow toxicity, occurred in 60 patients (31.4%). The incidence of infections did not increase. Patient survival was 93%, and graft survival was 88.2%. CONCLUSIONS: MMF is a potent and safe immunosuppressive agent in OLT recipients for rescue therapy in AR, CR, or chronic graft dysfunction and helps to reduce the serious toxic side effects of CNIs.

A survival-based scoring-system for initial graft function following orthotopic liver transplantation.

Initial graft function following orthotopic liver transplantation is a major determinant of postoperative survival and morbidity. Despite several efforts to provide scoring-systems for initial graft function, there is still a lack of a generally accepted classification scheme. The previously published systems assessed initial graft function based on the first postoperative days or weeks using liver-related laboratory parameters. It was shown that in most cases the scoring-systems did not correlate with patient survival. We intended to refine the definition of initial graft function in order to provide a survival based classification system. In a retrospective analysis of 761 patients following primary liver transplantation, a new scoring-system for early postoperative graft function was developed. Statistically significant differences in long term survival were calculated for ALAT, ASAT, bile production and prothrombin activity on days 1, 3, 7, 14. Points were then assigned according to the degree of survival: improved survival=1 point, poor survival=2 points. Patients were split into three groups corresponding to initially good, moderate and poor function. Applying this score, early and late patient survival rates and incidence of initial non-function were statistically significantly different. This was in contrast to the Gonzalez and the Ploeg-Maring classification scales, which are based on arbitrarily chosen cutoff levels. Retransplantation rates and postoperative morbidity were comparable both for the new and the older systems. We can conclude that the presented refined scoring-system for initial graft function provides a significant correlation to patient survival and initial non-function. We recommend the refined system for future studies.