Anorectal Manometry in 3D NEW! - Swiss-knife.org

36.7
Targeting oxygen free radical levels: a novel strategy for radical cytoreduction during hyperthermic
intraperitoneal chemotherapy (HIPEC)
K. Lehmann, A. Rickenbacher, J.-H. Jang, C. Oberkofler, R. Vonlanthen, R. Graf, P. Gertsch, P.-A. Clavien
(Zurich)
Objective: To tailor a cytotoxic therapy to cancer cells found in peritoneal carcinomatosis. Hyperthermic
intraperitoneal chemotherapy (HIPEC) is a therapy complementary to extensive peritoneal excision
of malignant tumors. HIPEC is performed after surgical cytoreduction by washing the peritoneum
with a hyperthermic (42°C) solution containing mitomycinC/doxorubicin or oxaliplatin targeting residual
tumor cells. However, many primary tumors respond poorly to these agents, therefore alternative
approaches to target chemo-resistant cells are needed. Reactive oxygen species (ROS) are a novel
approach to induce death of residual cancer cells.
Methods: Two human colon cancer cells (HT29 & SW403) were subjected to hyperthermia (42°C,
90min), and treated with a combination of mitomycinC/doxorubicin (each 10mg/L), oxaliplatin
(230mg/L), or induction of ROS by application of hydrogen peroxide (1-2mM) or the superoxide dismutase
(SOD) inhibitor diethyldithiocarbamate (DDC, 10-40mM).
Results: A series of experiments demonstrated that hyperthermia alone at 42°C had no cytotoxic effect,
but rapidly induced protective mechanisms, e.g. heat shock protein 70. Oxaliplatin and mitomycinC/doxorubicin
conferred inconsistent cytotoxicity depending on cell lines and doses. For example,
50% of HT29 cells were viable 7 days after hyperthermia with oxaliplatin. After treatment with mitomycinC/doxorubicin,
35% of SW403 cells remained viable. Hydrogen peroxide and the superoxide
dismutase inhibitor DDC consistently activated apoptotic pathways with increased cell death in combination
with HT, but showed no toxicity at physiologic temperatures. The effect on HT29 and SW403
cells was significantly superior compared with mitomycinC/doxorubicin or oxaliplatin. This suggests
that the combination of hyperthermia, together with low dose hydrogen peroxide or an SOD inhibitor,
is sufficient to exert cell death.
Conclusion: Standard chemotherapy confers variable effects depending on the type of cancer. In contrast,
strategies enhancing ROS were most effective and may represent a novel strategy overcoming
chemo-resistance of many tumor types.
36.8
Hepatobiliäre Komplikationen verbunden mit der Peritonektomie und der intraperitonealen hyperthermen
Chemotherapie
P. Piso (Regensburg/DE)
Objective: Bei ausgewählten Patienten mit einer Peritonealkarzinose kann die Prognose durch die
Durchführung einer parietalen und viszeralen Peritonektomie als chirurgische Zytoreduktion (CRS)
in Kombination mit einer hyperthermen intraperitonealen Chemotherapie (HIPEC) gegenüber der alleinigen
systemischen Chemotherapie verbessert werden. Bei der Operation müssen zum Teil auch
Eingriffe im rechten Oberbauch vorgenommen werden. Ziel der Arbeit war es, die spezifische Komplikationsrate
dieser Operationsschritte zu untersuchen.
Methods: Im Zeitraum 2005-2009 wurden 252 Patienten mittels CRS und HIPEC behandelt. Bei 63
Patienten wurden hepatobiliäre Eingriffe durchgeführt, davon bei 22 Leberresektionen, bei 39 Leberkapselresektionen
und bei 2 Gallengangsresektionen. Die Daten wurden retrospektiv analysiert.
Results: Das mediane Alter lag bei 49 Jahren. Die häufigsten Ursachen der Peritonealkarzinose waren
Appendix- (29 Patienten), Eierstock- (12 Patientinnen) bzw. Kolonkarzinome (11 Patienten). Die mediane
Operationsdauer lag bei 399 Minuten, die Dauer des Krankenhausaufenthaltes bei 24 Tage. Bei 20
Patienten traten keine postoperative Komplikationen auf. Der Rest der Patienten zeigte leichte (n=22)
oder schere (n=21) Komplikationen bestehend aus Fieber, Wundinfektionen oder Pleuraergüße bzw
Pankreatitis , Abszesse oder Nachblutungen. Galleleckagen wurden bei drei Patienten festgestellt,
jeweils einen Patienten aus den vorgestellten Subgruppen. Zwei Galleleckagen wurden operativ, eine
konservativ erfolgreich behandelt. Die Letalität lag bei den 63 Patienten bei 0%.
Conclusion: Chirurgische Resektionsverfahren im rechten Oberbauch sind im Rahmen der Peritonektomie
relativ häufig. Die spezifischen Komplikationen, z.B. Galleleckagen, sind mit 1,2% selten. Diese
können z.T. konservativ behandelt werden und gefährden den Patienten vital nicht.
36.9
Two stage oesophagectomy with laparoscopic gastrolysis reduced morbidity compared to one stage
open procedure
H. Gelpke, F. Grieder, M. Decurtins, D. Cadosch (Winterthur)
Objective: Oesophagectomy with gastric pull-up reconstruction remains associated with a morbidity
of up to 50% and a mortality of 5% to 10%. This is mainly due to pulmonary complications and anastomotic
leakage. We aimed to investigate whether laparoscopic ischemic conditioning of the stomach
reduces morbidity without compromising the quality of the surgical resection.
Methods: Retrospective analysis from November 2005 to October 2009 of 12 patients with oesophagus
cancer was performed. Six patients underwent one stage open oesophagectomy and six (after
2008) a two stage oesophagectomy with laparoscopic gastrolysis. Postoperative complications were
classified according to Dindo Clavien. As a measurement of the surgical quality the number of resected
lymph node and the type of resection were assessed.
Results: The two groups did not differ in terms of age, sex and ASA. Patients in the two stage group
had significantly fewer (33% vs. 100%, p=0.03) and less severe complications compared to the one
stage group. There were no differences in the number of resected lymph nodes (23 vs 22, p>0.05).
R0-resection was achieved in three patients in each group. The remaining patients had a R1-resection
(tumour within 1 mm of the circumferential resection margin).
Conclusion: Our study suggests that the two stage oesophagectomy with laparoscopic gastrolysis
may reduce morbidity without compromising the quality of the surgical resection compared to the one
stage procedure.
32 swiss knife 2010; 7: special edition
Research – Transplantation 37
37.1
Quantification of islet loss in syngeneic, allogeneic and xenogeneic grafts using iron-labeled islet
cells by 3T MRI
F. Ris 1 , L. Crowe 1 , Ph. Morel 1 , C. Toso 1 , S. Nielles-Vallespin 2 , P. Speier 2 , S. Masson 1 , M. Kocher 1 , D. Bosco 1 ,
J.-P. Vallee 1 , T. Berney 1 ( 1 Geneva, 2 Erlangen/DE)
Objective: Monitoring the fate of islet graft remains a major challenge. We developed a new MRI quantification
method at 3T, allowing follow-up of the graft. This protocol (dUTE) gives quantitative positive
contrast images for serial examination of iron-oxide labeled islet cells transplanted in rat and enables
quantification of rejection. The aim of the study was to compare evolution of the rejection in syngeneic,
allogeneic and xenogeneic models.
Methods: Syngeneic (SD, n=12), allogeneic (Lewis/Wistar, n=5) or xenogeneic (Lewis/Human, n=7)
grafts were performed after islet incubation with ferucarbotran (280ug/ml of iron). 3D UTE (0.07ms)
imaging gives high signal from all species. A second echo is subtracted resulting in positive contrast
from cells. Imaging was performed on a Siemens 3T clinical scanner, from the day after surgery up to
146 days under respiratory triggering. Quantitative assessment included automatic segmentation of
islet clusters. Exponential fit of data for each graft type was normalized to the initial scan.
Results: Both allogeneic (y=100e-0.03x) and xenogeneic (y=100e-0.05x) grafts show significant cell
loss over 42 days, unlike syngeneic grafts, as expected from rejection mechanisms. Rate of decay does
not depend on IEQ. After normalization, decay rates for each graft are significantly different (p