Juergen Tepel

Impact of Preoperative Physiological Risk Profile on Postoperative Morbidity and Mortality After Emergency Operation of Complicated Peptic Ulcer Disease

AimThe aim of this study was to evaluate the preoperative physiological risk profile for postoperative morbidity and mortality after emergency treatment of complicated peptic ulcer disease (PUD).MethodsOperative notes and hospital files of 261 patients—111 female, 150 male; median age 67 years (range 17–100 years)—undergoing an emergency operation from 1993 to 2005 were analyzed retrospectively. The physiologic subscore of the POSSUM score (POSSUM-phys) was analyzed with regard to predicting postoperative complications. Follow-up was obtained from questionnaires sent to family practitioners or by patient interviews.ResultsThe overall complication rate was 44%, and mortality was 24%. Among risk factors studied (e.g., sex, patient’s age, duration of symptoms, type of surgery), a high POSSUM-phys score was the strongest predictor for postoperative sepsis, anastomotic/suture dehiscence, postoperative bleeding, and mortality. Cut points for patients at risk could be calculated. Surgical procedures (organ-preserving versus resection) had no influence when matched for POSSUM-phys score. Nevertheless, organ resections were associated with higher scores. Recurrent PUD was a rare event (7.6%).ConclusionThe preoperative physiologic POSSUM score is a promising instrument for identifying patients at increased risk to develop major postoperative complications after emergency surgery for complicated PUD. Prospective studies are needed to prove its applicability for adjusting treatment to individual patients.

Adjuvant Treatment of Pancreatic Carcinoma in a Clinically Adapted Mouse Resection Model

Background: The high rate of local recurrence after radical resection of pancreatic adenocarcinoma fosters intensive efforts to develop new approaches for adjuvant treatment. The established animal models show significant limitations in simulating an adjuvant therapeutic setting. For optimal approximation to the clinical situation we therefore improved a murine orthotopic human xenotransplantation model. Methods: Subtotal pancreatectomy in mice was performed after orthotopic inoculation of human pancreatic cancer cells and manifestation of solid tumours. The natural course of disease, tumour growth and metastases were analysed. Gemcitabine as a cytotoxic drug was tested in vitro on the cell line used in this model and the effect of adjuvant treatment with gemcitabine in vivo was investigated. Results: All tumour-resected animals showed local recurrence. Organ metastases occurred in 67% in resected compared to 25% of non-resected animals. Gemcitabine in vitro was ineffective, but as adjuvant monotherapy resulted in a highly significant reduction of tumour weight and metastatic events. Conclusion: Subtotal pancreatectomy for xenotransplanted pancreatic cancer in SCID beige mice is feasible. Due to high rates of local recurrence and increased organ metastases, this model offers a relevant option for preclinical adjuvant testing, especially as in vitro and in vivo effects of cytotoxic drugs differ enormously.

Investigation of the Lith6 candidate genes APOBEC1 and PPARG in human gallstone disease

Background: Genetic susceptibility contributes to the aetiology of gallbladder diseases as shown by multiple epidemiological studies. A major gallstone susceptibility locus (Lith6) was identified in 2003 by quantitative trait locus mapping in mice. Two attractive positional and functional candidate genes in apolipoprotein B mRNA‐editing protein (APOBEC1) and peroxisome proliferator‐activated receptor γ (PPARG) are located in this interval.

Feasibility and Early Results of Interstitial Intensity-Modulated HDR/PDR Brachytherapy (IMBT) with/without Complementary External-Beam Radiotherapy and Extended Surgery in Recurrent Pelvic Colorectal Cancer

Background:A new multimodality treatment concept consisting of extended resection and postoperative fractionated intensity-modulated interstitial brachytherapy (IMBT) was introduced for pelvic recurrence of colorectal carcinoma.Patients and Methods:46 patients received extended resection and single plastic tubes were sutured directly onto the tumor bed. IMBT was started within 2 weeks postoperatively with a median dose of 24.5 Gy (5–35 Gy). Patients were treated either with high-dose-rate brachytherapy (HDR; n = 23) or with pulsed-dose-rate brachytherapy (PDR; n = 23). 25 patients received complementary 45-Gy external-beam irradiation (EBRT) to the pelvic region after explanting the plastic tubes.Results:Median follow-up was 20.6 months (7–107 months) and mean patient survival 25.7 ± 25.8 months (median 17, range 1–107 months). After 5 years overall survival, disease-free survival and local control rate were 23%, 20% and 33%, significantly influenced by the resectional state. There was a trend in favor of PDR compared to HDR, which reached statistical significance in patients who had not received additional EBRT.Conclusion:The combination of extended surgery and postoperative interstitial IMBT is feasible and offers effective interdisciplinary treatment of recurrent colorectal cancer. In this small and inhomogeneous cohort of patients PDR seems to be more effective than HDR, particularly when application of complementary EBRT is not possible. None of the patients who required resection of distant metastasis survived > 2 years in this study.Hintergrund:Zur Behandlung von Beckenrezidiven bei kolorektalen Karzinomen wurde die erweiterte chirurgische Resektion mit anschließender postoperativer fraktionierter intensitätsmodulierter interstitieller Brachytherapie (IMBT) als neuartige interdisziplinäre Behandlungsform entwickelt und in einer nicht randomisierten Beobachtungsstudie untersucht.Patienten und Methodik:46 Patienten erhielten eine erweiterte chirurgische Resektion im kleinen Becken mit direkter Aufnähung von Brachytherapieapplikatoren auf das clipmarkierte Tumorbett. Die Brachytherapie wurde postoperativ innerhalb von 2 Wochen mit einer mittleren Dosis von 24,5 Gy (5–35 Gy) begonnen. Die Patienten wurden entweder mit High-Dose-Rate-(HDR-)Brachytherapie (n = 23) oder mit Pulsed-Dose-Rate-(PDR-)Brachytherapie (n = 23) behandelt. Bei 25 Patienten wurde eine zusätzliche perkutane Bestrahlung des Beckens bis 45 Gy durchgeführt.Ergebnisse:Der mediane Nachbeobachtungszeitraum betrug 20,6 Monate (7–107 Monate) und das mittlere Überleben 25,7 ± 25,8 Monate (median 17, Bereich 1–107 Monate). Nach 5 Jahren lagen das Gesamtüberleben bei 23%, das krankheitsspezifische Überleben bei 20% und die lokale Tumorkontrolle bei 33%; sie wurden signifikant vom Resektionsstatus beeinflusst. Es zeigte sich ein Trend zugunsten der PDR-Brachytherapie im Vergleich zur HDR-Brachytherapie; dieser Trend war statistisch signifikant für Patienten, die keine zusätzliche perkutane Strahlentherapie erhielten.Schlussfolgerung:Die Kombination aus erweiterter chirurgischer Resektion und postoperativer interstitieller IMBT bietet eine wirksame Behandlungsmöglichkeit zur Therapie von Beckenrezidiven kolorektaler Karzinome. Hierbei scheint in diesem kleinen und sehr inhomogenen Patientengut die PDR-Therapie effektiver als die HDR-Therapie zu sein, insbesondere wenn keine zusätzliche perkutane Radiatio möglich ist. In dieser Studie überlebte keiner der Patienten, bei denen eine Resektion von Fernmetastasen erforderlich war, > 2 Jahre.

Modifikation der Leberresektionstechnik durch Radiofrequenzkoagulation

ZusammenfassungEinleitungNach wie vor stellt der intraoperative Blutverlust einen wichtigen Risikofaktor für die Morbidität und Letalität in der Leberchirurgie dar. Um diesen zu verringern, wurde die Technik der Radiofrequenzkoagulation unterstützend bei der Resektion eingesetzt.MethodenNach palpatorischer und sonographischer Exploration der Leber wurde das Parenchchym in der gekennzeichneten Resektionsebene mittels Radiofrequenztechnik koaguliert und nachfolgend durchtrennt. Auf diese Weise wurden 7 Patienten mit kolorektalen Metastasen behandelt.ErgebnisseIn allen Fällen konnte eine nahezu blutungsfreie Parenchymdurchtrennung durchgeführt werden. Zwei Patienten erhielten Erythrozytenkonzentrate aufgrund eines niedrigen Ausgangs-Hb sowie wegen eines ausgedehnten Begleiteingriffes. Als verfahrenspezifische Komplikationen wurde eine Verbrennung II° am Oberschenkel sowie eine postoperative Galleleckage, welche eine Hemihepatektomie erforderte, beobachtet.SchlussfolgerungDie radiofrequenzassistierte Resektion stellt, insbesondere bei erhöhter Blutungsneigung (Zirrhoseleber, Gerinnungsstörung), eine sinnvolle Erweiterung des technischen Repertoires in der Leberchirurgie dar.AbstractIntroductionSince the introduction of liver resection, intraoperative blood loss is considered to be a major risk factor for perioperative morbidity and mortality. Radiofrequency energy—an established technique for in situ ablation—was used to facilitate liver resection by creating a nearly bloodless tissue plane.MethodsAfter thorough manual and sonographic exploration of the liver, the planned and marked resection plane was coagulated by radiofrequency and then transected. Seven patients with liver metastases of colorectal carcinoma were operated on employing this technique.ResultsA nearly bloodless transection of the parenchyma could be achieved in all cases. Only two patients received blood transfusions: one due to a low preoperative hemoglobin and one due to extended additional abdominal surgery. Procedure-related complications included one case of a second-degree burn to the thigh and one case of postoperative bile leakage requiring hemihepatectomy.ConclusionsRadiofrequency-assisted resection offers a valuable additional option in liver surgery, especially in patients with an increased risk of intraoperative bleeding (cirrhosis, coagulopathy).

M2033 Blockade of TNF Alpha Reduces Pancreatic Tumor Growth and Metastasis in a Xenotransplantation Model

Inflammation and inflammatory cytokines accompany most solid cancers including pancreatic ductal adenocarcinoma (PDAC). In the present work we investigated the role of the major proinflammatory cytokine TNFalpha for the malignancy of PDAC cells In Vitro and In Vivo. In Vitro, TNFalpha strongly increased invasiveness of Colo357-, BxPc3and PancTuIcells while the anti-proliferative effect showed to be moderate. In Vivo, TNF alpha provoked a severe enhanced tumor growth and metastasis in mice bearing orthotopically growing PDAC. Inhibition of TNFalpha with infliximab or etanercept affected proliferation and invasiveness of PDAC cells In Vitro and revealed a strong anti-tumoral effects in SCID mice with Colo357-, BxPc3or PancTuI-tumors. Furthermore, after surgical resection of the PDAC tumors, we determined an even stronger therapeutic effect for both anti-TNF compounds. Infliximab-treatment reduced the volume of recurrent tumor by 70% and etanercept by almost 60%. Furthermore, both drugs strongly reduced the number of liver metastases. Thus, tumor cell-derived TNFalpha plays a profound role in malignancy of PDAC and inhibition of TNFalpha represents a promising therapeutic option particularly in adjuvant therapy after subtotal pancreatectomy.