Indications and successes of intestinal transplantation in children in the 21st century: A retrospective cohort study.

AIMS: To report the results and successes of intestinal transplantation (ITx) in the most active European centres, to emphasize that, although it is a difficult procedure, it should remain a therapeutic option for children with total, definitive and complicated intestinal failure when intestinal rehabilitation fails. METHODS: We retrospectively collected data about all patients less than 18 receiving an ITx from 2010 to 2022 in 8 centres, and outcomes in July 2022. RESULTS: ITx was performed in 155 patients, median age 6.9 years, in 45% for short bowel syndromes, 22% congenital enteropathies, 25% motility disorders, and 15% re-transplantations. Indications were multiple in most patients, intestinal failure-associated liver disease in half. The graft was in 70% liver-containing. At last follow up 64% were alive, weaned from parenteral nutrition, for 7.9 years; 27% had died and the graft was removed in 8%, mostly early after ITx. DISCUSSION: ITx, despite its difficulties, can give a future to children with complicated intestinal failure. It should be considered among the therapeutic options offered to patients with a predicted survival rate lower than that after ITx. Patients should be early discussed within multidisciplinary teams in ITx centres, to avoid severe complications impacting the results of ITx, or even to avoid ITx.

Liver Transplantation for Primary Sclerosing Cholangitis (PSC) With or Without Inflammatory Bowel Disease (IBD)-A European Society of Organ Transplantation (ESOT) Consensus Statement.

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines' Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.

[Liver metastases of neuroendocrine tumors]. / Lebermetastasen neuroendokriner Tumoren.

Neuroendocrine liver metastases (NELM) are very heterogeneous with respect to the clinical presentation and the prognosis. The treatment of NELMs requires a multidisciplinary approach and patients with NELM should be referred to a specialized center. When possible, the resection of NELMs provides the best long-term results. The general selection criteria for liver resection include an acceptable general physical condition for a large liver operation, tumors with a favorable differentiation grade 1 or 2, a lack of extrahepatic lesions, a sufficient residual liver volume and the possibility to resect at least 70% of the metastases. Supplementary treatment, including simultaneous liver ablation, are generally safe and can increase the number of patients who can be considered for surgery. For patients with resectable NELM, the resection of the primary tumor is recommended either in a 2-stage or combined procedure. In selected patients with nonresectable NELM a liver transplantation can be carried out, which can be associated with excellent long-term results.

MRI-guided percutaneous thermoablation as first-line treatment of recurrent hepatic malignancies following hepatic resection: single center long-term experience.

PURPOSE: Hepatic recurrence of liver malignancies is a leading problem in patients after liver resection with curative intention. Thermoablation is a promising treatment approach for patients after hepatic resection, especially in liver-limited conditions. This study aimed to investigate safety, survival, and local tumor control rates of MRI-guided percutaneous thermoablation of recurrent hepatic malignancies following hepatic resection. MATERIAL AND METHODS: Data from patients with primary or secondary hepatic malignancies treated between 2004 and 2018 with MRI-guided percutaneous thermoablation of hepatic recurrence after prior hepatic resection were retrospectively analyzed. Disease-free survival and overall survival rates were calculated using the Kaplan-Meier method. RESULTS: A total of 57 patients with hepatic recurrence (mean tumor size = 18.9 ± 9.1 mm) of colorectal cancer liver metastases (n = 27), hepatocellular carcinoma (n = 17), intrahepatic recurrence of cholangiocellular carcinoma (n = 9), or other primary malignant tumor entities (n = 4) were treated once or several times with MR-guided percutaneous radiofrequency (n = 52) or microwave ablation (n = 5) (range: 1-4 times). Disease progression occurred due to local recurrence at the ablation site in nine patients (15.8%), non-local hepatic recurrence in 33 patients (57.9%), and distant malignancy in 18 patients (31.6%). The median overall survival for the total cohort was 40 months and 49 months for the colorectal cancer group, with a 5-year overall survival rate of 40.7 and 42.5%, respectively. The median disease-free survival was 10 months for both the total cohort and the colorectal cancer group with a 5-year disease-free survival rate of 15.1 and 14.8%, respectively. The mean follow-up time was 39.6 ± 35.7 months. CONCLUSION: MR-guided thermoablation is an effective and safe approach in the treatment of hepatic recurrences in liver-limited conditions and can achieve long-term survival.

COVID-19 in cancer patients: clinical characteristics and outcome-an analysis of the LEOSS registry.

INTRODUCTION: Since the early SARS-CoV-2 pandemic, cancer patients have been assumed to be at higher risk for severe COVID-19. Here, we present an analysis of cancer patients from the LEOSS (Lean European Open Survey on SARS-CoV-2 Infected Patients) registry to determine whether cancer patients are at higher risk. PATIENTS AND METHODS: We retrospectively analyzed a cohort of 435 cancer patients and 2636 non-cancer patients with confirmed SARS-CoV-2 infection, enrolled between March 16 and August 31, 2020. Data on socio-demographics, comorbidities, cancer-related features and infection course were collected. Age-, sex- and comorbidity-adjusted analysis was performed. Primary endpoint was COVID-19-related mortality. RESULTS: In total, 435 cancer patients were included in our analysis. Commonest age category was 76-85 years (36.5%), and 40.5% were female. Solid tumors were seen in 59% and lymphoma and leukemia in 17.5% and 11% of patients. Of these, 54% had an active malignancy, and 22% had recently received anti-cancer treatments. At detection of SARS-CoV-2, the majority (62.5%) presented with mild symptoms. Progression to severe COVID-19 was seen in 55% and ICU admission in 27.5%. COVID-19-related mortality rate was 22.5%. Male sex, advanced age, and active malignancy were associated with higher death rates. Comparing cancer and non-cancer patients, age distribution and comorbidity differed significantly, as did mortality (14% vs 22.5%, p value < 0.001). After adjustments for other risk factors, mortality was comparable. CONCLUSION: Comparing cancer and non-cancer patients, outcome of COVID-19 was comparable after adjusting for age, sex, and comorbidity. However, our results emphasize that cancer patients as a group are at higher risk due to advanced age and pre-existing conditions.

[Rosai-Dorfman disease as a rare cause of a pancreatic mass]. / Die Rosai-Dorfman-Erkrankung als seltene Ursache für einen Pankreastumor.

The CT and MRI scans of a 70-year-old male patient revealed a mass in the pancreatic head and a 2.8-cm peripancreatic lymph node. Under steroid therapy the mass did not show regression. Finally, a pancreatoduodenectomy was performed. Histologically, Rosai-Dorfman disease (RDD) was diagnosed. RDD is a rare histiocytic disorder with usually nodal but sometimes also extranodal involvement. Herein we report a rare case of extranodal RDD with intrapancreatic localization.

Experiences of a multistep process with medical and psychological interventions for patients with congenital uterine aplasia to achieve motherhood: the Gothenburg-Tübingen collaboration.

Congenital uterine aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a condition associated to a non-functional uterus in the presence of functional ovaries. In a setting where surrogacy is illegal (or not accepted) and adoption is the only alternative, neovaginoplasty and subsequent uterus transplantation (UTx) can provide a route to motherhood for women with MRKHS. This review article describes a multistep process by which patients with MRKHS can achieve motherhood with their own biological child. This process involving a careful clinical diagnosis, psychological counselling, assessment of eligibility for neovagina creation and UTx, the surgical treatment, fertility treatment, and long-term follow-up was developed at the Tübingen University Hospital and in close collaboration with Sahlgrenska Academy, University of Gothenburg, Sweden, where the basic experimental and clinical groundwork for UTx was laid and the first-ever UTx procedure was performed.

[Role of the radiologist in surgery of colorectal liver metastases : What should be removed and what must remain]. / Rolle des Radiologen in der Chirurgie kolorektaler Lebermetastasen : Was soll weg und was muss übrig bleiben.

BACKGROUND: The radical resection of colorectal liver metastases is the only curative option for affected patients. If properly performed, surgery provides the chance of long-term tumor-free survival. OBJECTIVE: Summary of the critical interaction points between radiology and surgery in the planning and performance of (complex) liver resections. RESULTS: There are many interaction points between radiology and surgery in the treatment of patients with colorectal liver metastases. Radiology supports surgery by providing detailed information of the localization of metastases, information on liver inflow and outflow as well as basic information on liver quality and function. Perioperatively, it provides interventional treatment options for postoperative complications as well as ablation of non-resectable metastases. CONCLUSION: Complex liver resections can only be performed properly and successfully after thorough planning by an interdisciplinary board of surgeons, radiologists and associated disciplines.

[Diagnostics and management of intra-abdominal Echinococcus manifestation]. / Diagnostik und Management der intraabdominellen Echinococcus-Manifestation.

INTRODUCTION: Cystic and alveolar echinococcosis are two potentially life-threatening diseases caused by the helminthic parasites Echinococcus granulosus or Echinococcus multilocularis, respectively. In central Europe a marked increase in incidence of both forms of echinococcosis has recently been observed. OBJECTIVE: There is widespread uncertainty with diagnostic and treatment algorithms due to the close genetic relationship of both parasites and the similar presentation; however, since the treatment and prognosis significantly differ between the two diseases, a correct diagnosis is essential. This review summarizes the similarities and differences in the diagnostics and surgical treatment of these two parasites. RESULTS: The correct diagnosis is mainly based on patient history, radiological imaging and serological testing. In cystic echinococcosis cyst viability and stage determine whether treatment is medicinal, interventional, surgical or a watch and wait strategy. For alveolar echinococcosis surgical resection in combination with perioperative or adjuvant medicinal treatment is the gold standard and the only therapeutic option. As identification of the disease is often delayed due to the oligosymptomatic manifestation, complex resections are frequently necessary that need to be treated by a multidisciplinary team of experts. CONCLUSION: Echinococcosis is still a neglected disease due to the rarity and thus should be referred to experts in a tertiary hospital to avoid mistreatment or overtreatment. Due to a timely surgical, infectiological and interventional treatment in an interdisciplinary work-up, the prognosis of echinococcosis has significantly improved in recent years.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy combined with liver resection for concurrent peritoneal and hepatic metastases of gastrointestinal and gynecological primary tumors.

AIM OF THE STUDY: Cytoreductive surgery including liver resection and hyperthermic intraperitoneal chemotherapy provide survival benefit to selected patients but is associated with relevant morbidity and mortality rates. We aimed to report morbidity and mortality rates and parameters linked to increased morbidity. PATIENTS AND METHODS: Retrospective analysis of 37 patients who underwent liver resection and cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy between 2006 and 2016. From a prospectively collected database the morbidity and mortality rates and survival data were analyzed. RESULTS: The mortality rate was 0% and grade III-IV morbidity was 42%. Re-operation rate was 27%. Patients with complications tended to have a higher peritoneal cancer index (16 vs. 13; P=0.23). The performance of rectal resections was statistically significantly associated with morbidity (P=0.02). Neither performance of other type of resections nor the hyperthermic intraperitoneal chemotherapy compound nor the completeness of cytoreduction score was associated with elevated morbidity. No complications related to liver resections were observed. Furthermore, origin of peritoneal metastases did not impact on occurrence of complications. Median overall survival for colorectal primaries was 22 months (range, 9-60 months) and 30 months (range, 12-58 months) for ovarian cancer. CONCLUSION: Simultaneous resection of hepatic and peritoneal metastases seems to provide a survival benefit for selected patients and is associated with acceptable morbidity and mortality rates. Knowledge of patients and operative factors linked to morbidity will help to provide a strict selection process and a safer surgical procedure.

[Preconditioning of the liver]. / Präkonditionierung der Leber.

Posthepatectomy liver failure (PHLF) still represents a severe complication after major liver resection associated with a high mortality. In addition to an insufficient residual liver volume various factors play an important role in the pathophysiology of PHLF. These include the quality of the parenchyma, liver function, perfusion, i.e. maintenance of adequate inflow and outflow, as well as the condition of the patient and comorbidities. While the liver volume is relatively easy to evaluate using modern imaging techniques, the evaluation of liver function and liver quality require a differentiated approach. Both factors can be influenced by the constitutional status of the patient, medical history and previous treatment and must be given sufficient consideration in the risk evaluation. An adequate perfusion, e.g. portal and arterial circulation and adequate outflow by at least one hepatic vein as well an adequate biliary drainage should be always guaranteed in order to allow regeneration of the residual liver tissue. Only the understanding of all these aspects will support the surgeon in a correct and safe evaluation of the resectability. Additionally, the liver surgeon should be aware of all available perioperative and postoperative options to treat and to prevent PHLF. In this review article the most important questions regarding the risk factors related to PHLF are presented and the potential therapeutic and prophylactic management is described. The main goal is to ensure functional operability of the patient if oncological resectability is possible. In other words: in the case of correct oncological indication, the liver surgeon should be able to resect what is resectable or, alternatively, make resectable what primarily was not resectable.

Kidney Graft Salvage Strategies for Vascular Complications During Kidney Transplantation: A Single-center Experience.

BACKGROUND: Kidney-related unknown vascular injuries are rare and usually diagnosed only after reperfusion. Hemorrhage that makes in situ reconstruction impossible can lead to graft loss. In an era of organ shortage and an increasing number of patients on the waiting list for transplantation, a kidney graft salvage procedure consisting of graft nephrectomy, reperfusion, reconstruction, and reimplantation should be undertaken whenever possible as a contribution to extending the organs available for transplantation. METHODS AND PATIENTS: From January 2010 to December 2015, in total five patients suffered from intraoperative or immediate postoperative vascular complication and were included for this retrospective analysis. Age, sex, etiology of kidney failure, delayed graft function, kind of vascular complications and therapy, presence of aortoiliac calcification, cold and warm ischemia time, and length of hospital stay were analyzed. RESULTS: By applying this "one-step-back" procedure in three consecutive patients and a structured in situ repair in two patients, all grafts were saved. Two of five patients developed delayed graft function requiring hemodialysis. At discharge, graft function was excellent in all five patients. Reconstructed vasculature showed 100% patency. CONCLUSION: These graft salvage strategies are safe with excellent outcome and should be considered in the event of an acute vascular complication during kidney transplantation.

The protective effect of human renal sinus fat on glomerular cells is reversed by the hepatokine fetuin-A.

Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC. However, fetuin-A inverted these benign effects of RSFC from an anti- to a proinflammatory status. RSF was quantified by magnetic resonance imaging and liver fat content by 1H-MR spectroscopy in 449 individuals at risk for type 2 diabetes. Impaired renal function was determined via urinary albumin/creatinine-ratio (uACR). RSF did not correlate with uACR in subjects without NAFLD (n = 212, p = 0.94), but correlated positively in subjects with NAFLD (n = 105, p = 0.0005). Estimated glomerular filtration rate (eGRF) was inversely correlated with RSF, suggesting lower eGFR for subjects with higher RSF (r = 0.24, p < 0.0001). In conclusion, our data suggest that in the presence of NAFLD elevated fetuin-A levels may impair renal function by RSF-induced proinflammatory signalling in glomerular cells.

Portal Supply and Venous Drainage of the Caudate Lobe in the Healthy Human Liver: Virtual Three-Dimensional Computed Tomography Volume Study.

OBJECTIVE: The venous vascular anatomy of the caudate lobe is exceptional. The purpose of this study was to assess portal inflow and venous outflow volumes of the caudate lobe. METHODS: Extrahepatic (provided by the first-order branches) versus intrahepatic (provided by the second- to third-order branches) portal inflow, as well as direct (via Spieghel veins) versus indirect (via hepatic veins) venous drainage patterns were analyzed in virtual 3-D liver maps in 140 potential live liver donors. RESULTS: The caudate lobe has a greater intrahepatic than extrahepatic portal inflow volume (mean 55 ± 26 vs. 45 ± 26%: p = 0.0763), and a greater extrahepatic than intrahepatic venous drainage (mean 54-61 vs. 39-46%). Intrahepatic drainage based on mean estimated values showed the following distribution: middle > inferior (accessory) > right > left hepatic vein. CONCLUSIONS: Sacrifice of extrahepatic caudate portal branches can be compensated by the intrahepatic portal supply. The dominant outflow via Spieghel veins and the negligible role of left hepatic vein in caudate venous drainage may suggest reconstruction of caudate outflow via Spieghel veins in instances of extended left hemiliver live donation not inclusive of the middle hepatic vein. The anatomical data and the real implication for living donors must be further verified by clinical studies.

Pancreas-preserving surgical management of grade-C pancreatic fistulas after pancreatic head resection by external wirsungostomy.

PURPOSE: Completion pancreatectomy for grade-C pancreatic fistula is associated with unacceptably high mortality and therefore this strategy should be reassessed. This study presents an update of our experience with a pancreas-preserving technique in the course of salvage re-laparotomy in terms of closure of the open jejunum via segmental resection and external drainage of the pancreas. METHODS: Between April 2004 and January 2015, 292 pancreaticoduodenectomies (PD) with pancreaticojejunostomy (PJ) were performed. Thirteen patients (5 %) underwent salvage re-laparotomy for symptomatic grade-C fistulas, and clinical data were retrospectively analyzed. RESULTS: In all patients, the preservation of the pancreas remnant and external drainage of the pancreatic juice was feasible. Median hospital stay was 58 days (range, 21-142 days). In 4/13 patients (31 %), further reoperations were necessary. In-hospital mortality was 15 % (2/13). 3/13 patients (23 %) were readmitted and two received inpatient non-surgical treatment. To date re-pancreaticojejunostomy was performed in seven of the remaining 11 patients (63 %) after 168 days in median. In 1/7 patients (14 %), a re-operation after re-PJ was necessary. In one patient, externalization of the pancreas juice was chosen as a definite option. In another patient, secretion ceased spontaneously without stasis and normal endocrine function. Neither before nor after re-anastomosis impairment of endocrine function was observed. CONCLUSIONS: Closure of the intestinum and preservation of the pancreas remnant in grade-C pancreatic fistula is easy to perform and can be categorized as a life-saving procedure. Prevention of total pancreatectomy associated with high morbidity and mortality was achieved in all cases.

After Intestinal Transplantation Kidney Function Is Impaired by Downregulation of Epithelial Ion Transporters in the Ileum.

BACKGROUND: Intestinal transplantation is a treatment option for intestinal failure. Although nephrotoxic medication after transplantation is a major cause for posttransplant renal insufficiency, it remains unclear why kidney dysfunction is particularly frequent after intestinal transplantation. METHODS: This study analyzed messenger RNA expression of NHE3, DRA, and CFTR in 404 biopsies obtained between day 2 and 1508 from the terminal ileum of 10 adult intestinal transplant recipients. RESULTS: The time courses of immunosuppression and glomerular filtration rate were correlated. In the first posttransplant year, expression of NHE3 and DRA, which mediate NaCl absorption, was diminished to a greater degree than that of CFTR, which mediates chloride secretion. Reduced NHE3 and DRA expression was associated with high tacrolimus trough levels. Titration of tacrolimus to low levels by year 2 was paralleled by partially restored NHE3 and DRA expression. In cell culture experiments, similar effects of tacrolimus on transporter expression were detected. In patients, both reduced tacrolimus levels and recovery of NHE3 and DRA expression were associated with stabilization of renal function. CONCLUSIONS: Our data strongly suggest that tacrolimus impairs absorption of NaCl and water from the transplanted ileum, leading to volume depletion and impaired renal function. This may be reversible by reduction of tacrolimus to lower levels without increased rates of rejection or chronic graft failure.

Liver fluke-infested graft used for living-donor liver transplantation: case report and review of the literature.

Clonorchiasis is a cholangiopathy caused by foodborne trematode parasites, also known as liver flukes. Clonorchiasis is endemic in a wide geographical area extending from Eastern Europe to Southeast Asia. Infested hosts may remain asymptomatic for decades and consequently their liver can become available as a graft. To date, 20 liver transplantations with liver fluke-infested grafts have been reported in the literature. All of them occurred in Asian countries. We, here, report the first case to our knowledge in the Western world of living-donor liver transplantation (LDLT) with an Opisthorchis felineus-infested graft, and present a review of the literature. A 6-month-old girl with decompensated secondary biliary cirrhosis underwent an LDLT with a left lateral graft infested with O. felineus. After prompt diagnosis and adequate therapy, both donor and recipient had an uneventful postoperative course and long-term follow-up. Liver grafts infested with liver flukes do not pose a contraindication to liver donation from deceased or living donors, provided that a correct diagnosis and treatment are performed in a timely fashion.

Polymorphisms in PLA2G6 and PLA2G4C genes for calcium-independent phospholipase A2 do not contribute to attenuated niacin skin flush response in schizophrenia patients.

We hypothesized that attenuated niacin skin flushing in schizophrenia patients might be associated with polymorphic variants in PLA2G6 and PLA2G4C genes (rs4375 and rs1549637 variations) which encode calcium-independent phospholipase A2 beta (iPLA2ß) and cytosolic phospholipase A2 gamma (cPLA2γ) enzymes. The iPLA2ß and cPLA2γ may play an important role in niacin-mediated signaling; in addition to their major role - mediating phospholipids remodeling, which alters membrane receptors and signal transduction, they regulate the reservoir of arachidonic acid for prostaglandins synthesis. Skin response to topical niacin of 0.1M, 0.01M, 0.001M and 0.0001M concentrations in 75 schizophrenia patients was rated using the method of volumetric niacin response (VNR). Neither PLA2G6 nor PLA2G4C gene polymorphisms were significantly associated with VNR values. Furthermore, polymorphisms׳ synergy on niacin skin flushing was also not detected.