Search

ZusammenfassungNeuroendokrine Neoplasien (NEN) bilden eine heterogene Gruppe maligner Tumoren, die überwiegend dem gastro-entero-pankreatischen System (GEP) zuzuordnen sind. Hierbei sind Dünndarm und Pankreas die häufigsten Organe für Primärtumoren, die Leber stellt den dominanten Metastasierungsort dar. Da viele Patient*innen lange asymptomatisch bleiben, führen oftmals zufällig diagnostizierte Lebermetastasen oder ein Ileus zur Diagnose. Die einzige kurative Therapieoption stellt die komplette Entfernung von Primarius und Metastasen dar. Besonders im Falle der metastasierten Erkrankung sollten die vorhandenen Therapieoptionen immer im interdisziplinären Tumorboard mit Spezialisten*innen aus Gastroenterologie, (Leber-)Chirurgie, Radiologie, Nuklearmedizin, Radiotherapie, Pathologie und Endokrinologie evaluiert werden. Durch die Kombination der verschiedenen Therapieverfahren kann auch für Patient*innen mit fortgeschrittener Erkrankung eine jahrelange Prognose bei guter Lebensqualität erreicht werden. Wichtig für die Therapieentscheidung sind neben patientenindividuellen Faktoren der Differenzierungsgrad des Tumors, dessen hormonelle Sekretion, das Metastasierungsmuster und der Erkrankungsverlauf. Die Behandlung von Lebermetastasen umfasst neben den unterschiedlichen chirurgischen Strategien die lokal-ablativen radiologischen und nuklearmedizinischen Verfahren, die als Ergänzung zu den systemischen Therapien zur Verfügung stehen.

ZusammenfassungThoraxkompressionsbedingte Verletzungen im Zuge einer kardiopulmonalen Reanimation umfassen vor allem Läsionen der Haut und des knöchernen Thoraxes. Schwere und lebensbedrohliche Komplikationen einer Reanimation sind jedoch ebenfalls beschrieben. Wir berichten von einer 65-jährigen Patientin, die aufgrund eines Myokardinfarkts einen Herz-Kreislauf-Stillstand erlitt und unter dem Einsatz eines externen Thoraxkompressionsgerätes (Lund University Cardiac Arrest System [LUCAS]) erfolgreich reanimiert werden konnte. Thoraxkompressionsbedingt kam es zu einem Gallenblasenausriss mit Leberlazerationen, die im Verlauf zu einem hämorrhagischen Schock führten, was mittels einer FAST-Ultraschalluntersuchung diagnostiziert und in einer Notfalllaparotomie therapiert werden konnte. Wir empfehlen ein standardisiertes Prozedere bei der Versorgung von Patienten nach Erreichen eines ROSC.

Indications for liver resection in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) vary from liver resection with curative intent to tumor debulking or tissue sampling for histopathological characterization. With increasing expertise, the number of minimally invasive liver surgeries (MILS) in GEP-NET patients has increased. However, the influence on the oncological outcome has hardly been described. The clinicopathological data of patients who underwent liver resection for hepatic metastases of GEP-NET at the Department of Surgery, Charité—Universitätsmedizin Berlin, were analyzed. Propensity score matching (PSM) was performed to compare MILS with open liver surgery (OLS). In total, 22 patients underwent liver surgery with curative intent, and 30 debulking surgeries were analyzed. Disease-free survival (DFS) was longer than progression-free survival (PFS) (10 vs. 24 months), whereas overall survival (OS) did not differ significantly (p = 0.588). Thirty-nine (75%) liver resections were performed as OLS, and thirteen (25%) as MILS. After PSM, a shorter length of hospital stay was found for the MILS group (14 vs. 10 d, p = 0.034), while neither DFS/PFS nor OS differed significantly. Both curative intended and cytoreductive resection of hepatic GEP-NET metastases achieved excellent outcomes. MILS led to a reduced length of hospital, while preserving a good oncological outcome.

Timing of parathyroidectomy (PTX) remains controversial in candidates for kidney transplant with concomitant renal hyperparathyroidism (HPT). The aim of this retrospective study was to identify the influence of early vs late posttransplant PTX compared to pretransplant PTX on renal graft function and morbidity.This single-center cohort study includes 57 patients with renal HPT and kidney transplantation treated between 2007 and 2017. Ninety-six patients had surgery for renal HPT between 2007 and 2017 as a consecutive sample. Group 1 (n = 30; tertiary HPT), group 2 (n = 66; secondary HPT). Of group 1, 4 patients were excluded for PTX before and after kidney transplantation. In group 2, 20 patients were excluded since they had not undergone kidney transplantation during follow-up. Twelve patients were excluded because of short follow-up (kidney transplantation in 2018), and 3 patients were excluded because of transplant failure within 90 days. Twenty-six patients underwent posttransplant PTX (10 patients within 12 months after transplant), and 31 patients had undergone PTX prior to kidney transplantation. Graft function, serum calcium concentrations, parathyroid hormone (PTH) levels, postoperative morbidity, and 90-day mortality were recorded.Median age was 53.1 years in group 1 and 49.1 years in group 2. Most patients were male (53.8% in group 1; 54.8% in group 2). Median preoperative PTH levels were significantly different with 331.6 pg/mL in group 1 and 667.5 pg/mL in group 2 (P = .003). Creatinine levels changed little from 1.4 mg/dL (range, 0.8-2.5) to 1.7 mg/dL (range, 0.7-7.3) in group 1, and no difference was seen between early or late PTX after transplantation. In group 2, creatinine levels were 8.5 mg/dL (range, 4.6-11.7) before PTX and 8.7 mg/dL (range, 5.1-11.9) after PTX. We saw no correlation between postoperative PTH and kidney function. Thirty-five patients with postoperative PTH 15 pg/mL displayed a mean postoperative creatinine of 5.5 mg/dL (range, 4.3-6.8), similar to other patients. Both the 30-day and 90-day mortality rates were zero.PTX had no negative effect on graft function, whether performed before or after (early or late) kidney transplantation. Surgical cure of renal HPT should be performed as soon as possible to prevent secondary complications and can also be safely carried out early after transplantation.

Neuroendocrine neoplasias comprise a heterogenous group of malignant tumours, mostly arising from the gastro-entero-pancreatic system (GEP). Most of these tumours develop from the small intestine and pancreas and the liver is the predominant site for distant metastases. Patients may be asymptomatic for a long time and liver metastases are frequently diagnosed by chance or during operations for bowel obstruction, for example, during emergency surgery. The only curative therapy consists in complete removal of primary and metastases. In case of metastatic disease, various treatment modalities need to be discussed in interdisciplinary tumour boards comprised of specialists from gastroenterology, (liver-)surgery, radiology, nuclear medicine, radiotherapy, pathology and endocrinology. By combining different therapies, even patients with progressive disease may reach long-term overall survival with good quality of life. The most important factors for decisions on therapy are individual factors like tumour grading, hormonal functionality, type of metastases and evolution of the disease. Adequate treatment of liver metastases comprises various surgical strategies as well as locally ablative radiological interventions and nuclear medical therapies, in complement to systemic treatments.Neuroendokrine Neoplasien (NEN) bilden eine heterogene Gruppe maligner Tumoren, die überwiegend dem gastro-entero-pankreatischen System (GEP) zuzuordnen sind. Hierbei sind Dünndarm und Pankreas die häufigsten Organe für Primärtumoren, die Leber stellt den dominanten Metastasierungsort dar. Da viele Patient*innen lange asymptomatisch bleiben, führen oftmals zufällig diagnostizierte Lebermetastasen oder ein Ileus zur Diagnose. Die einzige kurative Therapieoption stellt die komplette Entfernung von Primarius und Metastasen dar. Besonders im Falle der metastasierten Erkrankung sollten die vorhandenen Therapieoptionen immer im interdisziplinären Tumorboard mit Spezialisten*innen aus Gastroenterologie, (Leber-)Chirurgie, Radiologie, Nuklearmedizin, Radiotherapie, Pathologie und Endokrinologie evaluiert werden. Durch die Kombination der verschiedenen Therapieverfahren kann auch für Patient*innen mit fortgeschrittener Erkrankung eine jahrelange Prognose bei guter Lebensqualität erreicht werden. Wichtig für die Therapieentscheidung sind neben patientenindividuellen Faktoren der Differenzierungsgrad des Tumors, dessen hormonelle Sekretion, das Metastasierungsmuster und der Erkrankungsverlauf. Die Behandlung von Lebermetastasen umfasst neben den unterschiedlichen chirurgischen Strategien die lokal-ablativen radiologischen und nuklearmedizinischen Verfahren, die als Ergänzung zu den systemischen Therapien zur Verfügung stehen.

The surgical removal of diseased parathyroid glands is the only curative treatment for primary and secondary hyperparathyroidism. Before an intervention, the confirmed diagnosis and an accurate localization are decisive for selection of the appropriate procedure. After appropriate localization diagnostics, a focussed intervention is possible for primary hyperparathyroidism, whereby every intervention must be controlled by intraoperative monitoring of parathyroid hormone. Reoperations or multiple glandular disease necessitate a differentiated approach with appropriate prior diagnostics.Die operative Entfernung erkrankter Nebenschilddrüsen stellt die einzige kurative Therapie beim primären und sekundären Hyperparathyreoidismus dar. Vor einem Eingriff sind die sichere Diagnose und eine gute Lokalisationsdiagnostik entscheidend, um das passende Vorgehen zu wählen. Beim primären Hyperparathyreoidismus ist nach entsprechender Lokalisationsdiagnostik eine fokussierte Intervention möglich, wobei jeder Eingriff durch ein intraoperatives Parathormonmonitoring abgesichert wird. Reoperationen oder Mehrdrüsenerkrankungen erfordern ein differenzierteres Vorgehen mit entsprechender Vordiagnostik.

Background Adrenal sarcomas are rare malignant tumors with structural and clinical similarities to sarcomatoid adrenocortical carcinoma. Preoperative diagnosis of tumors of the adrenal gland can be challenging and often misleading thus detaining patients from appropriate oncological strategies. Objective This analysis of a case series evaluated the predictive capability of the primary clinical diagnosis in case of malignancies of the adrenal gland. Methods Thirty two patients were treated from 2009 to 2015 at our clinic and analyzed retrospectively. All patients had computed tomography and/or magnet resonance imaging and a primary histopathological examination at our institution after surgery. Ten questionable cases were surveyed by a reference pathologist. Results Twelve out of 32 diagnoses had to be revised (37.5%). Only 15 out of 24 tumors primarily classified as adrenocortical carcinoma were finally described as primary adrenal cancer. We found two leiomyosarcomas, one liposarcoma, one sarcomatoid adrenocortical carcinoma, and one epitheloid angiosarcoma among 12 misleading diagnoses. Other tumors turned out to be metastases of lung, hepatocellular, and neuroendocrine tumors. Larger tumors were significantly more often correctly diagnosed compared to smaller tumors. Four patients of the group of revised diagnoses died whereas all patients with confirmed diagnoses survived during the follow-up. Conclusion Preoperative assessment of tumors of the adrenal gland is still challenging. In case of wrong primary diagnosis, the prognosis could be impaired due to inadequate surgical procedures or insufficient preoperative oncological treatment.

Background and Aims: There are only few data on the influence of cinacalcet on the outcome of parathyroidectomy in patients with renal hyperparathyroidism. Indication and timing of surgery have changed since its introduction, especially with regard to kidney transplantation. Therefore, we retrospectively analyzed patients undergoing parathyroidectomy for renal hyperparathyroidism in our institution. Material and methods: Between 2008 and 2015, 196 consecutive operations in 191 patients were analyzed. About 80 operations (41%) were performed in patients receiving cinacalcet compared with 116 operations (59%) in patients without cinacalcet. Clinical data, preoperative medication, pre- and postoperative laboratory values, type and details of surgery including complications, as well as cardiovascular complications and kidney transplantation with graft function were recorded. Results: Demographical data were similar in patients with or without cinacalcet treatment. A total of 54% of patients received a kidney graft before or after parathyroidectomy. Pre- and postoperative parathormone levels were similar in both groups (preoperatively 755 vs 742 ng/L, postoperatively 50 vs 46 ng/L, p > 0.10), whereas patients with cinacalcet showed significantly lower calcium levels preoperatively (2.28 vs 2.41 mmol/L, p = 0.0002). There was no difference in recurrence or persistence of hyperparathyroidism, duration of surgery, hospital stay, or complication rate. Creatinine levels in patients with tertiary hyperparathyroidism were similar after 1-year follow-up. Conclusion: Cinacalcet did not influence outcome of patients with parathyroidectomy for renal hyperparathyroidism and can be safely offered to patients not responding to medical treatment.

Neuroendocrine tumors (NET) are rare and demonstrate variable clinical behavior depending on the degree of tumor differentiation. Patients with poorly differentiated tumors (NET G3) have a poor prognosis. Systemic treatment with cytotoxic chemotherapy is considered to be the treatment of choice. In patients that are refractory or intolerant to first-line therapy, experts recommend peptide receptor radionuclide therapy (PRRT) in tumors that express somatostatin receptors. Recently, combinations of PRRT and chemotherapy were tested in patients with NET. Available data have reported promising tumor control rates and an excellent toxicity profile in cases where PRRT had been administered with capecitabine/temozolomide, even when administered as salvage therapy. The current study reported an exceptional case of advanced NET G3 with severe toxicity upon receiving PRRT in combination with capecitabine/temozolomide as third line therapy. The patient developed a life-threatening neutropenic fever, fungal pneumonia and necrotizing mastitis 23 days after the first cycle of therapy was administered. However, the treatment led to a significant reduction in tumor size. A total of 5 months after treatment initiation, the patient was alive and in excellent clinical condition with sustained tumor response. In summary, the current study presented a rare case of high grade NET exhibiting an almost complete response to PRRT in combination capecitabine/temozolomide, despite facing unexpected severe toxicity.

Background. Minimally invasive thyroid and parathyroid resections are rarely performed. Promising new endoscopic transoral approaches to the anterior neck (transoral endoscopic thyroidectomy vestibular approach [TOETVA]) have been described with good results and few complications. This study evaluates a new device to allow the safe entrance of trocars in the subplatysmal space for TOETVA in a cadaver model. Methods. The technique was performed in 4 unilateral thyroidectomies in female cadavers. The technical steps consisted of a 10-mm incision made at the center of the oral vestibule followed by subplatysmal hydrodissection. The blunt dissector is a metallic stick with an olive at the end and promotes progressive gain in subplatysmal space enlarging the operative field. The instrument was inserted creating a space below the platysma to the anterior neck and the strap muscles. Three trocars were inserted in the vestibular area. The dissection begins by cutting the linea alba cervicalis. The isthmus was dissected and transected. Anatomical structures as the superior thyroid artery, parathyroid glands, and the recurrent laryngeal nerve could be safely identified with magnified vision. Results. Optimal operative field due to subplatysmal dissection by the device allowed for exposition of thyroid and parathyroid glands in all cases. Unilateral thyroidectomy was performed in a mean of 54 minutes with excellent aesthetic results. Conclusions. The new device is a promising feature to allow safe transoral thyroid surgery in a cadaver model. Further studies in clinical series are needed to evaluate the broad application of the device.

Minimal-invasive Schilddrusen- und Nebenschilddrusenresektionen bei gutartigen und bosartigen Tumoren werden selten durchgefuhrt. In jungster Zeit wurden vielversprechende neue endoskopische transorale Ansatze am vorderen Hals mit guten Ergebnissen und geringen Komplikationsraten beschrieben. Diese Studie beschreibt die erste klinische Serie in Deutschland mit der transoralen endoskopischen Thyreoidektomie („transoral endoscopic thyroidectomy – vestibular approach“, TOETVA) und zeigt technische Probleme und Losungen auf. Die Technik wurde fur Hemithyreoidektomien bei Patienten ohne vorhergehende Halsoperationen indiziert. Die technischen Schritte bestanden aus einem 10 mm langen Schnitt an der Innenseite der Unterlippe, gefolgt von einer subplatysmalen Hydrodissektion. Dann wurde ein stumpfer Dissektorstab eingefuhrt, der einen Raum zwischen Platysma und infrahyoidaler Muskulatur schaffte. Uber die Zugange an der Innenseite der Unterlippe wurden pramental drei Trokare (ein Optiktrokar, zwei Arbeitstrokare) eingesetzt. Nach der Teilung der geraden Muskulatur wurde der Schilddrusenisthmus durchtrennt. Anatomische Strukturen wie die A. thyroidea superior, die Nebenschilddrusen und der N. laryngeus reccurens konnten mit entsprechender Vergroserung am Monitor problemlos identifiziert werden. Intermittierendes Neuromonitoring wurde zur Vermeidung einer Nervus-laryngeus-recurrens-Parese routinemasig eingesetzt. Durch die subplatysmale Dissektion ergab sich ein optimales Operationsfeld zur Darstellung von Schilddruse und Nebenschilddrusen. Mehrere kritische Schritte und passende Losungen wurden definiert. 1. Position des Teams und technische Verbesserung durch den Einsatz eines 4K-Laparoskopieturms, der eine bessere Sicht auf die Anatomie ermoglicht, insbesondere bei der Praparation des N. laryngeus recurrens; 2. laterale und kraniale Positionierung der seitlichen Trokare zur Vermeidung einer Lasion des Nervus mentalis; 3. initiale Hydrodissektion des subplatysmalen Raumes; 4. Verwendung eines Dissektors, der schrittweise das Operationsfeld im anterioren zervikalen Bereich schafft; 5. die infrahyoidale Muskulatur wird mithilfe ausen fixierter Haltenahte zuruckgezogen; 6. intraoperatives Neuromonitoring, das routinemasig uber die Trokare oder perkutan durch eine 1 mm Inzision durchgefuhrt wird; 7. Extraktion des Praparates mittels eines Bergebeutels; 8. Drainagen sind moglich, konnen aber bei kleinem Operationsfeld vermieden werden. Die neue TOETVA-Technik ist eine gute Option fur selektierte Patienten, um transorale Schilddrusen- und Nebenschilddrusenoperationen durch den vestibularen pramentalen Zugang zu ermoglichen. Weitere klinische Studien sind notig, um Indikationen und Sicherheit der Technik zu evaluieren.

The incidence of neuroendocrine tumors (NET) increases with age. Lately, the diagnosis of NET was mainly caused by early detection of small NET (

The aim of this study was to investigate the influence of immunosuppression following orthotopic liver transplantation (OLT) on course of inflammatory bowel disease (IBD) including disease activity and complications.Out of 1168 patients undergoing liver transplantation between 1988 and 2000 at our center, we identified those with IBD (n = 67). In a comparative cohort study, IBD patients after OLT were compared to controls without OLT. All drugs including immunosuppressive and anti-inflammatory medication and complications during follow-up were recorded in 6-month intervals. Also, surgical interventions before and after OLT as well as endoscopic interventions with macroscopic and microscopic findings were collected and analyzed. Additionally, development of malignant neoplasias was recorded.Of the 67 individuals with IBD and OLT, 41 were available for analyses and compared with 42 controls. The mean follow-up was 7.4 (range: 3 - 15) years. Short-term therapy with calcineurin inhibitors or mycophenolate mofetil led to short-term remission, yet sustained remission could only be achieved in patients receiving mycophenolate mofetil. At 14.5 years, clinical remission was reached by significantly more patients in the transplant group (54 %) than in the control group (33 %, p = 0.0295). Patients in the control group required nearly 2 times as many surgical interventions related to IBD than patients in the transplant group. Neoplasias were more common in the OLT (n = 8) compared with 4 solid organ cancers in the control group, respectively.Our data demonstrate an overall positive impact of immunosuppression following OLT on the course of IBD, especially with mycophenolate mofetil, but an increased rate of malignancies.Die vorliegende Studie untersucht den Einfluss der Immunsuppression nach Lebertransplantation auf den Verlauf chronisch entzündlicher Darmerkrankungen insbesondere hinsichtlich entzündlicher Aktivität und Komplikationen.Von 1168 Patienten, die zwischen 1988 und 2000 in unserem Zentrum lebertransplantiert wurden, hatten 67 eine chronisch entzündliche Darmerkrankung (CED). In einer Fall-Kontroll-Analyse wurden diese Patienten mit CED-Patienten ohne Lebertransplantation (LTx) verglichen. Im Beobachtungszeitrum wurden alle Immunsuppressiva und anti-inflammatorischen Medikamente sowie Komplikationen in 6-Monats-Intervallen erfasst. Auch chirurgische und endoskopische Eingriffe mit mikro- und makroskopischen Befunden wurden erfasst und analysiert, ebenso wie das Auftreten von Malignomen.Von den 67 Patienten mit CED und LTx konnten 41 analysiert und mit 42 Kontroll-Patienten verglichen werden. Der Beobachtungszeitrum lag im Mittel bei 7.4 Jahren (3 – 15 Jahre). Eine anhaltende Remission konnte nur bei Patienten mit MycophenolatMofetil erzielt werden. Nach 14.5 Jahren hatten signifikant mehr Patienten aus der Transplant-Gruppe (54 %) eine klinische Remission ihrer CED (p = 0.0295). Patienten der Kontrollgruppe mussten sich nahezu doppelt so vielen chirurgischen Eingriffen unterziehen, wie die Patienten der Transplant-Gruppe. Malignome entwickelten sich öfter in der Transplant-Gruppe (n = 8), als in der Kontrollgruppe (n = 4), allerdings nicht signifikant.Unsere Daten zeigen einen günstigen Einfluss der Immunsuppression nach Lebertransplantation auf den Verlauf der CED, insbesondere mit MycophenolatMofetil als Kombinationstherapie.

Introduction: Gender has been proven to influence the pathophysiology and treatment of numerous diseases, including kidney diseases and hormonal dysfunction like hyperparathyroidism. Thus, higher parathormone levels have been demonstrated in women with end-stage kidney disease, when compared to men. Objectives: We questioned whether female gender is associated with an increased risk for parathyroid nodular hyperplasia and necessary parathyroidectomy in dialysis patients and assessed demographics as well as outcome data for women and men undergoing parathyroidectomy for renal hyperparathyroidism. Patients and Methods: One hundred and thirty patients (men = 75, female = 55) with end-stage renal disease on chronic dialysis and advanced secondary hyperparathyroidism who underwent parathyroidectomy between 2008 and 2014 at our center were analyzed retrospectively. Perioperative characteristics and short-term outcome were evaluated with respect to biological gender. Results: No differences could be demonstrated for patient demography, comorbidities and the perioperative course between males and females. Only preoperative calcium levels were lower in female than in male patients (2.3 ± 0.19 vs. 2.3 ± 0.26, p = 0.04). There were more women, however, with cerebrovascular complications during follow-up (p = 0.04). There was no postoperative mortality, and all complications and comorbidities with exception of cerebrovascular diseases were equally distributed between female and male patients. Conclusion: Overall, we could not demonstrate many significant differences between male and female patients with end-stage renal diseases, chronic dialysis and operated secondary hyperparathyroidism. Only preoperative electrolyte levels were higher in male than in female patients, and cerebrovascular complications developed more often in females than in males during long-term follow-up.

Introduction Livers discarded after standard organ retrieval are commonly used as a cell source for hepatocyte transplantation. Due to the scarcity of organ donors, this leads to a shortage of suitable cells for transplantation. Here, the isolation of liver cells from diseased livers removed during liver transplantation is studied and compared to the isolation of cells from liver specimens obtained during partial liver resection. Methods Hepatocytes from 20 diseased explanted livers (Ex-group) were isolated, cultured and stored at 4°C for up to 48 hours, and compared to hepatocytes isolated from the normal liver tissue of 14 liver lobe resections (Rx-group). The nonparenchymal cell fraction (NPC) was analyzed by flow cytometry to identify potential liver progenitor cells, and OptiPrep™ (Sigma-Aldrich) density gradient centrifugation was used to enrich the progenitor cells for immediate transplantation. Results There were no differences in viability, cell integrity and metabolic activity in cell culture and survival after cold storage when comparing the hepatocytes from the Rx-group and the Ex-group. In some cases, the latter group showed tendencies of increased resistance to isolation and storage procedures. The NPC of the Ex-group livers contained considerably more EpCAM+ and significantly more CD90+ cells than the Rx-group. Progenitor cell enrichment was not sufficient for clinical application. Conclusions Hepatocytes isolated from diseased explanted livers showed the essential characteristics of being adequate for cell transplantation. Increased numbers of liver progenitor cells can be isolated from diseased explanted livers. These results support the feasibility of using diseased explanted livers as a cell source for liver cell transplantation.

Objectives Patients who have a liver transplant for primary sclerosing cholangitis may develop recurrent disease and biliary complications, organ loss necessitating revision liver transplant, or death. We evaluated long-term outcomes in patients who had liver transplant for primary sclerosing cholangitis. Materials and methods In 71 patients who had a liver transplant for end-stage liver disease because of primary sclerosing cholangitis, a retrospective review was done to evaluate biliary complication-free survival, transplanted organ survival, and death. Human leukocyte antigen typing and matching were reviewed. Results There were 39 patients (55%) who had biliary complications, loss of the liver transplant, or death at a mean 12.1 years after transplant. The 5- and 10-year event-free survival reached 74.6% and 45% (53 patients after 5 years, and 32 patients after 10 years). Male sex of transplant recipients was a significant risk factor for biliary complications, revision liver transplant, or death. Most patients had inflammatory bowel disease, primarily ulcerative colitis. The human leukocyte antigen profile or number of mismatches had no effect on complication-free survival. Conclusions Biliary complications, revision liver transplant, and death are a useful combined primary endpoint for recurrent primary sclerosing cholangitis after liver transplant.

Cell morphology, proliferation and motility, as well as mono- and heterotypic cell-to-cell interactions, are of increasing interest for in vitro experiments. However, tightly controlling culture conditions whilst simultaneously monitoring the same set of cells is complicated. Moreover, video-microscopy of distinct cells or areas of cells over a prolonged period of time represents a technical challenge. The SlideObserver was designed for cinemicrography of cells in co-and monoculture. The core elements of the system are the SlideReactors, miniaturised hollow fibre-based bioreactors operated in closed perfusion loops. Within the SlideReactors, cells can be cultured under adaptable conditions as well as in direct- and indirect co-culture. The independent perfusion loops enable controlled variation of parameters such as medium, pH, and oxygenation. A combined automated microscope stage and camera set-up allows for micrograph acquisition of multiple user-defined regions of interest within the bioreactor units. For proof of concept, primary cells (HUVEC, human hepatocytes) and cell lines (HuH7, THP-1) were cultured under stable and varying culture conditions, as well as in mono- and co-culture. The operational system enabled non-stop imaging and automated control of process parameters as well as elective manipulation of either reactor. As opposed to non-perfused culture systems or comparable devices for cinemicrographic analysis, the SlideObserver allows simultaneous morphological monitoring of an entire culture of cells in multiple bioreactors.

Micrometer-sized iron oxide particles (MPIOs) attract increasing interest as contrast agents for cellular tracking by clinical Magnetic Resonance Imaging (MRI). Despite the great potential of MPIOs for in vivo imaging of labeled cells, little is known on the intracellular localization of these particles following uptake due to the lack of techniques with the ability to monitor the particle uptake in vivo at single-cell level. Here, we show that coherent anti-Stokes Raman scattering (CARS) microscopy enables non-invasive, label-free imaging of MPIOs in living cells with sub-micron resolution in three dimensions. CARS allows simultaneous visualization of the cell framework and the MPIOs, where the particles can be readily distinguished from other cellular components of comparable dimensions, and localized inside the cell.

Labeling of hepatocytes with micron-sized iron oxide particles (MPIOs) enables cell detection using clinical magnetic resonance equipment. For clinical applications, large numbers of cells must be labeled in a simple and rapid manner and have to be applied in suspension. However, all existing protocols are based on adhesion culture labeling with subsequent resuspension, only suitable for small experimental settings. The aim of this study was to investigate the feasibility of preparing MPIO-labeled primary human hepatocytes in a temporary suspension culture. Human hepatocytes were isolated from 16 donors and labeled with MPIOs in suspension, using the Rotary Cell Culture System. Particle incorporation was investigated by light and electron microscopy. Cells were compared with adhesion culture-labeled and subsequently enzymatically resuspended cells. During a period of 5 days, hepatocyte-specific parameters of cell damage (aspartate aminotransferase and alanine aminotransferase) and metabolic activity (urea and albumin) were analyzed (n = 7). Suspension cultures showed a higher outcome in cell recovery compared with the conventional labeling method. When incubated with 180 particles/viable cell for 4 h, the mean particle uptake was 28.8 particles/cell at a labeling efficiency of 95.1%. Labeling in suspension had no adverse effects on cell integrity or metabolic activity. We conclude that labeling of human hepatocytes in suspension is feasible and simple and may serve future large-scale processing of cells.

To evaluate the safety and efficacy of the Amplatzer vascular plug (AVP) for embolization of the splenic artery in patients with hepatic hypoperfusion after orthotopic liver transplantation (OLT).Thirteen patients (9 men and 4 women) with a mean age of 56 years (range 22-70) who developed splenic artery syndrome after OLT with decreased liver perfusion and clinically relevant impairment of liver function (increased transaminase or serum bilirubin levels, thrombocytopenia, and/or therapy-refractory ascites) were treated by embolization of the proximal third of the splenic artery using the AVP. The plugs ranged in diameter from 6 to 16 mm, and they were introduced through femoral (n = 9), axillary (n = 3), or brachial (n = 1) access using a 5F or 8F guiding catheter.The plugs were successfully placed, and complete occlusion of the splenic artery was achieved in all patients. Placement of two plugs was necessary for complete occlusion in 3 of the 13 patients. Occlusion took on average 10 min (range 4-35). There was no nontarget embolization or plug migration into more distal segments of the splenic artery. All patients showed improved arterial perfusion, including the liver periphery, on postinterventional angiogram. After embolization, liver function parameters (transaminase and bilirubin levels) improved with normalization of concomitant thrombocytopenia and a decrease in ascites volume.Our initial experience in a small patient population with SAS suggests that the AVP enables precise embolization of the proximal splenic artery, thus providing safe and effective treatment for poor liver perfusion after OLT due to SAS.

The purpose of this study was to evaluate the accuracy of MDCT for preoperative assessment of hepatic vascular anatomy and the identification of liver-transplantation (OLT) patients at risk of developing subsequent splenic artery steal syndrome (SASS). A total of 145 patients with liver cirrhosis who had undergone OLT and had pre-operative three-phase MDCT (4- to 64-rows) within 100 days before OLT were enrolled retrospectively. MDCT and 3Ds were reviewed by two independent blinded observers (O1/O2). Pre-operative imaging findings were correlated with intra-operative results; findings indicative for SASS were correlated with clinical data and DSA. Among all 145 patients, 16 patients (11%) showed accessory hepatic arteries (accuracy O1/O2, 97%; with 3Ds, 100%); 32 (22%) patients had replaced hepatic arteries (accuracy O1, 97%; O2, 95%; with 3Ds, 100%; kappa = 0.87 and 0.89, P0.001). Among 119 patients, 12 patients developed SASS after OLT. The logistic regression model revealed the spleen volume (P = 0.0105) as a predictive factor of SASS. With spleen volumesor=829 ml, an accuracy of 75% for prediction of SASS was obtained. MDCT with three-dimensional post-processing (3Ds) was highly accurate for pre-operative hepatic vessel evaluation in patients before OLT. In addition, spleen volume was a predictive factor for developing SASS after OLT.

Objectives: Stable long-term functioning of liver cells after transplantation in humans is still not achieved successfully. A new approach for successful engraftment of liver cells may be the transplantation of syngeneic cells into an allogeneic liver graft. We therefore developed a new rat model for combined liver and liver cell transplantation (cLCTx) under stable immunosuppression. Materials and Methods: After inducing a mitotic block, liver grafts from female donor rats (Dark Agouti) were transplanted into female recipients (Lewis). In male Lewis rats, liver cell proliferation was induced with subsequent cell isolation and transplantation into female recipients after organ transplantation. Y-chromosome detection of the transplanted male cells was performed by quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FisH) with localization of transplanted cells by immunohistochemistry. Results: Immunohistochemistry demonstrated the engraftment of transplanted cells, as confirmed by FisH, showing repopulation of the liver graft with 15.6% male cells (± 1.8 SEM) at day 90. qPCR revealed 14.15% (± 5.09 SEM) male DNA at day 90. Conclusion: Engraftment of transplanted syngeneic cells after cLCTx was achieved for up to 90 days under immunosuppression. Immunohistochemistry indicated cell proliferation, and the FisH results were partly confirmed by qPCR. This new protocol in rats appears feasible for addressing long-term functioning and eventually the induction of operational tolerance in the future.

Anastomotic leaks after oesophagojejunostomy usually are treated by endoluminal stenting with self-expandable metal or plastic stents. Here we present a patient with more than 4 years of oesophageal stenting for anastomotic leakage after gastrectomy. During the attempted removal of the stent he experienced a perforation of the jejunum. Emergency surgery with complete resection of the stent and transhiatal oesophagojejunostomy was performed. Generally, early removal of oesophageal stents 4-6 weeks after implantation is recommended, as later attempts often fail and may lead to extensive surgery.

Cellular therapies require methods for noninvasive visualization of transplanted cells. Micron-sized iron oxide particles (MPIOs) generate a strong contrast in magnetic resonance imaging (MRI) and are therefore ideally suited as an intracellular contrast agent to image cells under clinical conditions. However, MPIOs were previously not applicable for clinical use. Here, we present the development and evaluation of silica-based micron-sized iron oxide particles (sMPIOs) with a functionalizable particle surface. Particles with magnetite content of >40% were composed using the sol-gel process. The particle surfaces were covered with COOH groups. Fluorescein, poly-l-lysine (PLL), and streptavidin (SA) were covalently attached. Monodisperse sMPIOs had an average size of 1.18 μm and an iron content of about 1.0 pg Fe/particle. Particle uptake, toxicity, and imaging studies were performed using HuH7 cells and human and rat hepatocytes. sMPIOs enabled rapid cellular labeling within 4 h of incubation; PLL-modified particles had the highest uptake. In T2*-weighted 3.0 T MRI, the detection threshold in agarose was 1,000 labeled cells, whereas in T1-weighted LAVA sequences, at least 10,000 cells were necessary to induce sufficient contrast. Labeling was stable and had no adverse effects on labeled cells. Silica is a biocompatible material that has been approved for clinical use. sMPIOs could therefore be suitable for future clinical applications in cellular MRI, especially in settings that require strong cellular contrast. Moreover, the particle surface provides the opportunity to create multifunctional particles for targeted delivery and diagnostics.

Impaired hepatic arterial perfusion after orthotopic liver transplantation (OLT) may lead to ischemic biliary tract lesions and graft-loss. Hampered hepatic arterial blood flow is observed in patients with hypersplenism, often described as arterial steal syndrome (ASS). However, arterial and portal perfusions are directly linked via the hepatic arterial buffer response (HABR). Recently, the term 'splenic artery syndrome' (SAS) was coined to describe the effect of portal hyperperfusion leading to diminished hepatic arterial blood flow. We retrospectively analyzed 650 transplantations in 585 patients. According to preoperative imaging, 78 patients underwent prophylactic intraoperative ligation of the splenic artery. In case of postoperative SAS, coil-embolization of the splenic artery was performed. After exclusion of 14 2nd and 3rd retransplantations and 83 procedures with arterial interposition grafts, SAS was diagnosed in 28 of 553 transplantations (5.1%). Twenty-six patients were treated with coil-embolization, leading to improved liver function, but requiring postinterventional splenectomy in two patients. Additionally, two patients with SAS underwent splenectomy or retransplantation without preceding embolization. Prophylactic ligation could not prevent SAS entirely (n = 2), but resulted in a significantly lower rate of complications than postoperative coil-embolization. We recommend prophylactic ligation of the splenic artery for patients at risk of developing SAS. Post-transplant coil-embolization of the splenic artery corrected hemodynamic changes of SAS, but was associated with a significant morbidity.

Resections of the pancreatic head are still associated with relatively high postoperative infection rates. Irrespective of the technique, pylorus-preserving pancreticoduodenectomy (PPPD) or Whipple procedure, about 10% of patients develop intra-abdominal abscess.1 Even in good series, another 10% of patients experience wound infections.2 However, these numbers can be much higher if other complications, such as pancreatic fistula or delayed gastric emptying, occur.3 The majority of the observed infections are caused by bacteria from the gut, especially Enterococci and Escherichia coli,4 which translocate into mesenteric lymph nodes or into the blood. Several conditions before, during, or after pancreas resection facilitate bacterial translocation: decreased postoperative intestinal motility, jaundice, and use of antibiotics resulting in small bowel bacterial overgrowth,5 loss of mucosal barrier function caused by malnutrition, manipulation of the bowel and parenteral nutrition,6 and suppression of the immune system caused by blood products and operative trauma.7 Probiotics (living bacteria) are able to influence all 3 pathogenic mechanisms of bacterial translocation: they increase intestinal motility, stabilize the intestinal barrier (feeding of enterocytes, production of omega-3-fatty acids, stimulation of mucus secretion),8 and enhance the innate immune system (induction of IL-10, inhibition of T-helper-1 cell generation by dendritic cells,9 activation of macrophages, stimulation of secretory IgA and neutrophils with reduction of inflammatory cytokines10). Prebiotics (fibers) reach the colon untouched and serve as colonic food that will be fermented by probiotics to omega-3-fatty acids and other important nutrients.7 Therefore, prebiotics and probiotics are potentially useful in prevention of bacterial infections following pancreas resections. We previously reported from 2 randomized trials in patients following major abdominal surgery or liver transplantation a significant reduction in infections with a synbiotic composition consisting of one lactic acid bacteria (Lactobacillus plantarum 299) and one fiber (oat fiber), compared with parenteral or enteral nutrition without symbiotics.11,12 As probiotic strains are able to act synergistically,13 different bacterial strains were tested for their potential usefulness in clinical trials. Only 8 tested strains could survive the transport through the gastrointestinal tract and produce sufficient antimicrobial substances. Four lactic acid bacteria were chosen to form a synbiotic composition (two lactobacilli, one Pediococcus, and one Leuconostoc) together with 4 fibers, known for their strong bioactivities: betaglucan, inulin, pectin, and resistant starch.14,15 The present study was carried out to investigate whether this combination is safe and effective in patients following PPPD.

Summary Older liver grafts are often discarded because of conservative selection criteria. We report on our clinical experience with graft-age related outcome. Patients transplanted with livers older than 70 years (70.2–80.2 years, n = 38) were compared with controls transplanted with livers younger than 70 years. Pairs were matched for age, gender, indication and cold ischemic time. Mean donor age was 73.4 ± 2 vs. 39 ± 16 years. Patient and graft survival did not differ between both groups after 1-year follow-up (P = 0.19 and P = 0.24 respectively). Retransplantation rate was 10.5% vs. 5.3% (P = 0.40). Initial poor function occurred in two patients in the study group versus four patients in the control group (P = 0.69). The incidence of rejection episodes was comparable. Parameters of cholestasis and protein synthesis showed no difference 1-year post-transplant. Mean age of donor organs in matched pairs group B was near by half of that in the older donor group A (39.0 vs. 73.4 years). Post-transplant outcome as indicated by patient and graft survival was comparable between both groups. Donor organ age had no impact on postoperative organ function. We recommend to accept liver grafts from organ donors older than 70 years to expand the donor pool.

Background Hemostasis is a central issue in laparoscopic surgery. Ultrasonic scissors and bipolar clamps are commonly used, with known advantages with each technique. Methods The prototype of new surgical scissors, delivering ultrasonically generated frictional heat energy and bipolar heat energy simultaneously (THUNDERBEAT® [TB]), was compared to ultrasonic scissors (Harmonic ACE® [HA]) and an advanced bipolar device (LigaSure® [LS]) using a pig model. As safety parameters, temperature profiles after single activation and after a defined cut were determined. As efficacy parameters, seal failures and the maximum burst pressure (BP) were measured after in vivo sealing of vessels of various types and diameters (categories 2–4 and 5–7 mm). Moreover, the vertical width of the tissue seal was measured on serial histological slices of selected arteries. The cutting speed was measured during division of isolated arteries and during dissection of a defined length of compound tissue (10 cm of mesentery). Burst-pressure measurement and histological analysis were performed by investigators blinded to the used sealing device. Results Using the TB, the burst pressure in larger arteries was significantly higher (734 ± 64 mmHg) than that of the HA (453 ± 50 mmHg). No differences in the rate of seal failures were observed. The cutting speed of the TB was significantly higher than that of all other devices. Safety evaluation revealed temperatures below 100 °C in the bipolar device. The maximum temperature of the HA and the TB was significantly higher. No relevant differences were observed between the HA and the TB. Conclusions The ultrasonic and bipolar technique of the TB has the potential to surpass the dissection speed of ultrasonic devices with the sealing efficacy of bipolar clamps. However, heat production that is comparable to conventional ultrasonic scissors should be minded for clinical use.