Hepatic arterial infusion with nanoliposomal irinotecan leads to significant regression of tumor size of colorectal liver metastases in a CC531 rat model.

Long-term therapy for unresectable colorectal liver metastases remains challenging. Intraarterial treatments aim to avoid systemic adverse effects of chemotherapy. Nanoliposomal cytotoxic drugs manage to increase the drug concentration within the tumor while reducing toxicity in healthy tissue.  In this study we analyzed the effect of hepatic arterial infusion (HAI) with nanoliposomal irinotecan with or without the combination of embolization particles in a rat model for colorectal liver metastases. For the study 32 WAG/Rij rats received subcapsular tumor implantation with CC531 rat colonic adenocarcinoma cells. After ten days tumor size was assessed via ultrasound and animals underwent HAI. One group served as control receiving NaCl 0.9 % (Sham), the three treatment groups received either nanoliposomal irinotecan (HAI nal iri), Embocept® S (HAI Embo) or Embocept® S and nanoliposomal irinotecan (HAI Embo+nal iri). Three days after treatment animals were sacrificed after assessment of tumor size. As a result all treatment groups showed a significant reduction in tumor growth compared to Sham (p<0.05). Expression of the apoptosis marker caspase-3 was enhanced in HAI nal iri and HAI Embo+nal iri compared to Sham and HAI Embo and  even significantly enhanced after HAI Embo+nal iri in comparison to Sham (p<0.05). We were able to show that HAI with Embocept® S led to significantly reduced tumor growth while HAI with nanoliposomal irinotecan alone or in combination with Embocept® S even led to a reduction of tumor size. Thus, we demonstrate that intraarterial treatment with nanoliposomal irinotecan effectively inhibits tumor growth in a rat model of colorectal liver metastases and demands further investigation.

Intra-arterial EmboCept S® and DC Bead® effectively inhibit tumor growth of colorectal rat liver metastases.

BACKGROUND: Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases. METHODS: Eight days after subcapsular implantation of 5 × 105 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses. RESULTS: On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid. CONCLUSION: The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.

Hepatic arterial infusion of irinotecan and EmboCept® S results in high tumor concentration of SN-38 in a rat model of colorectal liver metastases.

Intraarterial chemotherapy for colorectal liver metastases (CRLM) can be applied alone or together with embolization particles. It remains unclear whether different types of embolization particles lead to higher intratumoral drug concentration. Herein, we quantified the concentrations of CPT-11 and its active metabolite SN-38 in plasma, liver and tumor tissue after hepatic arterial infusion (HAI) of irinotecan, with or without further application of embolization particles, in a rat model of CRLM. Animals underwent either systemic application of irinotecan, or HAI with or without the embolization particles Embocept® S and Tandem™. Four hours after treatment concentrations of CPT-11 and SN-38 were analyzed in plasma, tumor and liver samples by high-performance liquid chromatography. Additionally, DNA-damage and apoptosis were analyzed immunohistochemically. Tumor tissue concentrations of SN-38 were significantly increased after HAI with irinotecan and EmboCept® S compared to the other groups. The number of apoptotic cells was significantly higher after both HAI with irinotecan and EmboCept® S or Tandem™ loaded with irinotecan compared to the control group. HAI with irinotecan and EmboCept® S resulted in an increased SN-38 tumor concentration. Both HAI with irinotecan and EmboCept® S or Tandem™ loaded with irinotecan were highly effective with regard to apoptosis.

[Incidence and Predictive Factors for Bilaterality in Patients with Papillary Thyroid Carcinoma]. / Inzidenz und prädiktive Faktoren des bilateralen papillären Schilddrüsenkarzinoms.

BACKGROUND: The optimal extent of thyroidectomy for papillary thyroid cancer (PTC) ≥ 10 mm und < 10 mm is still controversial. Therefore, the purpose of this study was to investigate factors predictive for bilaterality in patients with papillary thyroid carcinoma (PTC). MATERIAL AND METHODS: We retrospectively reviewed 123 PTC patients in a single centre study who underwent either completion or total thyroidectomy and analysed the predictive value of tumour size, histological parameters, multifocality, and lymph node metastases with primary tumour size of ≥ 10 mm and < 10 mm as well as for ≥ 7 mm and < 7 mm. RESULTS: Out of 123 patients, 26 exhibited bilateral PTC. This was significantly more frequent in patients with a primary tumour size of ≥ 10 mm (77%) compared to a tumour size of < 10 mm (23%) (p = 0.004). Multifocality was found to be an independent predictive factor for bilaterality (p = 5.022e-18). Metachronous lymph node metastases showed a trend for bilateral PTCs (p = 0.0691). These findings were reproducible for the comparison between the ≥ 7 mm and < 7 mm group. CONCLUSION: The presence of bilateral PTC appears to be related to the size of the primary tumour ≥ 10 mm. Multifocality is a positive predictor for bilaterality. When multifocality, even with a primary tumour size of < 10 mm, is observed in patients with PTC, total thyroidectomy or completion thyroidectomy may be considered. If lobectomy is performed in patients with PTC, meticulous follow-up is needed to detect hidden malignancies in the contralateral lobe.

Portal branch ligation does not counteract the inhibiting effect of temsirolimus on extrahepatic colorectal metastatic growth.

The mTor-inhibitor temsirolimus (TEM) has potent anti-tumor activities on extrahepatic colorectal metastases. Treatment of patients with advanced disease may require portal branch ligation (PBL). While PBL can induce intrahepatic tumor growth, the effect of PBL on extrahepatic metastases under TEM treatment is unknown. Therefore, we analyzed the effects of TEM treatment on extrahepatic metastases during PBL-associated liver regeneration. GFP-transfected CT26.WT colorectal cancer cells were implanted into the dorsal skinfold chamber of BALB/c-mice. Mice were randomized to four groups (n = 8). One was treated daily with TEM (1.5 mg/kg), PBS-treated animals served as controls. Another group underwent PBL of the left liver lobe and received daily TEM treatment. Animals with PBL and PBS treatment served as controls. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied over 14 days. In non-PBL animals TEM treatment inhibited tumor cell proliferation as well as vascularization and growth of the extrahepatic metastases. PBL did not influence tumor cell engraftment, vascularization and metastatic growth. Of interest, TEM treatment significantly reduced tumor cell engraftment, neovascularization and metastatic groth also after PBL. PBL does not counteract the inhibiting effect of TEM on extrahepatic colorectal metastatic growth.

Tumour growth of colorectal rat liver metastases is inhibited by hepatic arterial infusion of the mTOR-inhibitor temsirolimus after portal branch ligation.

Portal branch ligation (PBL) can be performed before major hepatic resection of colorectal liver metastases (mCRC) to increase the remnant liver mass. However, PBL may also stimulate mCRC growth through hepatic arterial hyperperfusion and growth factor release. Herein, we studied whether hepatic arterial infusion (HAI) of the mTOR-inhibitor temsirolimus (Tem) is capable of inhibiting the growth of colorectal liver metastases after PBL. WAG/Rij rats were randomized to four groups (n=6 each) and underwent subcapsular implantation of 5×10(5) CC531 cells into the left liver lobe. The animals of two groups underwent simultaneous PBL of the tumour bearing liver lobe. Ten days later animals underwent a HAI either of temsirolimus (Tem and PBL Tem) or saline solution (Sham and PBL Sham). Tumour size was analyzed at days 10 and 13 using three-dimensional ultrasound. In Sham controls tumour volume increased by 43%. After PBL Sham tumour volume increased by 52%. In contrast, in animals undergoing HAI of temsirolimus the tumour growth was not only completely inhibited, but tumour volume was found decreased, irrespective of PBL. After HAI of temsirolimus immunohistochemistry revealed an increased cleaved caspase-3 activity, indicating stimulation of apoptotic cell death. In parallel temsirolimus treatment was associated with a significant reduction of PECAM-1 positive cells within the tumour tissue, implying a reduced tumour vascularisation. HAI of temsirolimus is capable of inhibiting the growth of CC531 colorectal rat liver metastases also after PBL.

Intrahepatic cholangiocarcinoma in a transplant liver--selective internal radiation therapy followed by right hemihepatectomy: report of a case.

Intra- or extrahepatic cholangiocarcinomas are the second most common primary liver malignancies behind hepatocellular carcinoma. Whereas the incidence for intrahepatic cholangiocarcinoma is rising, the occurrence of extrahepatic cholangiocarcinoma is trending downwards. The treatment of choice for intrahepatic cholangiocarcinoma remains liver resection. However, a case of liver resection after selective internal radiation therapy in order to treat a recurrent intrahepatic cholangiocarcinoma in a transplant liver is unknown in the literature so far. Herein, we present a case of a patient undergoing liver transplantation for Wilson's disease with an accidental finding of an intrahepatic cholangiocarcinoma within the explanted liver. Due to a recurrent intrahepatic cholangiocarcinoma after liver transplantation, a selective internal radiation therapy with yttrium-90 microspheres was performed followed by right hemihepatectomy. Four years later, the patient is tumor-free and in a healthy condition.

Successful management of postoperative necrotizing pancreatitis after infrarenal abdominal aortic aneurysm repair.

We present a case of severe necrotizing pancreatitis that developed after elective repair of an abdominal aortic aneurysm. Surgeons are confronted in cases of postoperative acute pancreatitis with the dilemma of potential intraabdominal infection and the high risk of a subsequent infection of the retroperitoneal synthetic material. The therapeutic options range from a restrictive regime to radical necrosectomy and multivisceral resection.

Hepatic arterial infusion of temsirolimus inhibits tumor growth of colorectal rat liver metastases even after a growth stimulating procedure like liver resection.

BACKGROUND: Hepatic arterial infusion (HAI) of specific anti-tumor drugs can be more effective compared with systemic drug application. Herein, we studied whether HAI of temsirolimus is effective to inhibit tumor growth of colorectal liver metastases after liver resection. MATERIALS AND METHODS: Twenty-four Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats were randomized to four groups and underwent subcapsular implantation of CC531 colorectal cancer cells in the left liver lobe. In two groups, a 70% liver resection (Phx) was performed simultaneously. After 10 d, animals received either a HAI of temsirolimus (CCI-779) or saline solution (controls). Tumor growth was determined on d 10 and 13 using three-dimensional ultrasound. On d 13, tumor tissue was removed for histologic and immunohistochemical analysis. RESULTS: Sham controls revealed a tumor growth of ∼40% from d 10 to d 13. HAI of temsirolimus completely inhibited this tumor growth. Controls with Phx showed a tumor growth of >60%. In contrast, HAI of temsirolimus in Phx animals did not only inhibit tumor growth but was even capable of decreasing the tumor size by ∼8%. Immunohistochemical analysis of the tumors showed a decreased proliferation rate and an increased cleaved caspase-3 activity, which was associated with a significant reduction of platelet endothelial cell adhesion molecule (PECAM)-1-positive cells after HAI of temsirolimus. CONCLUSIONS: HAI of temsirolimus inhibits tumor growth of CC531 colorectal liver metastases even if a growth-stimulating procedure like Phx is performed. Inhibition of tumor growth is provided by a decrease of tumor vascularization associated with an inhibition of tumor cell proliferation and an induction of tumor cell apoptosis.

Comparison of self-gated and prospectively triggered fast low angle shot (FLASH) sequences for contrast-enhanced magnetic resonance imaging of the liver at 9.4 T in a rat model of colorectal cancer metastases.

OBJECTIVE: The aim of this study was to compare a retrospectively self-gated fast low angle shot sequence (RSG-FLASH) with a prospectively triggered fast low angle shot sequence (PT-FLASH) using an external trigger device for dynamic contrast-enhanced magnetic resonance imaging of the liver at 9.4 T in a rat model of colorectal cancer metastases. MATERIALS AND METHODS: In 10 rats with hepatic metastases, we acquired an axial RSG-FLASH sequence through the liver. A FLASH sequence with prospective triggering (PT-FLASH) using an external trigger device was acquired at the same location with the same imaging parameters. After intravenous injection of 0.2 mmol/kg body weight of Gd-DTPA, alternating acquisitions of both sequences were performed at 4 consecutive time points.Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and lesion enhancement were obtained for liver tumors and parenchyma. In addition, we assessed the total acquisition times of the different imaging approaches for each acquisition, including triggering and gating. Two independent readers performed a qualitative evaluation of each sequence. Statistical analyses included paired t tests and Wilcoxon matched pairs signed rank tests. RESULTS: No statistically significant differences in SNR, CNR, or lesion enhancement were observed. Qualitative assessments of the sequences were comparable. However, acquisition times of PT-FLASH were significantly longer (mean [SD], 160.6 [25.7] seconds; P < 0.0001) and markedly variable (minimum, 120 seconds; maximum, 209 seconds), whereas the RSG-FLASH approach demonstrated a constant mean (SD) acquisition time of 59.0 (0) seconds. CONCLUSIONS: The RSG-FLASH and PT-FLASH sequences do not differ qualitatively or quantitatively regarding SNR, CNR, and lesion enhancement for magnetic resonance imaging of the liver in the rats at 9.4 T. However, the variability of acquisition times for the PT-FLASH sequences is a major factor of inconsistency, and we therefore consider this approach as inappropriate for dynamic contrast-enhanced studies with multiple-measurement time points. In contrast, the RSG-FLASH sequence represents a fast, consistent, and reproducible technique suitable for contrast-agent kinetic studies in experimental small-animal imaging of the abdomen.

Liver-directed chemotherapy of cetuximab and bevacizumab in combination with oxaliplatin is more effective to inhibit tumor growth of CC531 colorectal rat liver metastases than systemic chemotherapy.

Colorectal carcinoma is, through to its high rate of liver metastasis (mCRC), the second most cause of cancer death worldwide. Tumor resection represents the only potential cure. In cases of unresectable disease systemic chemotherapy (sCHT) remains the therapy of choice. Modern sCHT regimens including biological agents can induce tumor response that leads to curative surgery of initially unresectable mCRC. However, liver-directed therapy via hepatic arterial infusion (HAI) may produce higher response rates than sCHT. Herein we studied whether a HAI of cetuximab (CE) plus bevacizumab (BE) with or without oxaliplatin (OX) can inhibit tumor growth in a rat model. WAG/Rij rats underwent subcapsular hepatic tumor implantation. After 10 days animals received either HAI or sCHT of CE plus BE, OX or all three drugs. Saline-treated animals served as controls. Tumor growth was estimated at day 10 and 13. On day 13 liver and tumor tissue was studied histologically and immunohistochemically. In controls the tumors grew about 50 %. OX alone was not capable of inhibiting tumor growth. In contrast, CE plus BE given as HAI significantly reduced tumor growth compared to sCHT (p < 0.05). HAI of CE plus BE combined with OX yielded an even more pronounced inhibition of tumor growth. Immunohistochemistry revealed a decreased tumor cell proliferation and tumor vascularization. The present study demonstrates that HAI of CE plus BE is effective to inhibit tumor growth. This effect is even more pronounced in combination with OX. Systemic application of these agents cannot achieve comparable effects.

Hepatic arterial infusion but not systemic application of cetuximab in combination with oxaliplatin significantly reduces growth of CC531 colorectal rat liver metastases.

PURPOSE: Systemic chemotherapy still represents the gold standard in the treatment of irresectable colorectal liver metastases. Modern anticancer agents like the monoclonal antibody cetuximab have improved the outcome of patients in clinical studies. As hepatic arterial infusion (HAI) is capable to potentially increase the anticancer effect of cytostatics, we herein studied whether HAI of cetuximab (CE) as a single agent or in combination with oxaliplatin (OX) exerts increased anticancer effects compared to the systemic application (SYS) of the drugs. METHODS: WAG/Rij rats were randomized to eight groups and underwent 10 days after subcapsular hepatic tumor implantation either HAI or SYS of CE, OX, or the combination of both agents (CE + OX). Saline-treated animals served as controls. Tumor volume was measured at days 10 and 13 using three-dimensional ultrasound. On day 13, liver and tumor tissue was sampled for histological and immunohistochemical analysis. RESULTS: In controls, the tumor volume significantly increased from day 10 to 13. Application of OX alone via HAI or SYS did not inhibit tumor growth compared to controls. SYS of CE or CE + OX did also not reduce tumor growth. In contrast, HAI of CE and CE + OX significantly inhibited tumor growth. HAI of CE significantly reduced tumor vascularization as measured by the number of platelet endothelial cell adhesion molecule-1-positive cells and significantly increased the number of apoptotic tumor cells as measured by the cellular caspase-3 expression. CONCLUSION: HAI of CE and CE + OX reduces tumor growth of colorectal rat liver metastases involving the inhibition of angiogenesis and induction of tumor cell apoptosis.

Parenchyma-preserving hepatic resection for colorectal liver metastases.

BACKGROUND: Hepatic resection of colorectal liver metastases is the only curative treatment option. As clinical and experimental data indicate that the extent of liver resection correlates with growth of residual metastases, the present study analyzes the potential benefit of a parenchyma-preserving liver surgery approach. METHODS: Data from a prospectively maintained database of patients undergoing liver resection for colorectal metastases were reviewed. Evaluation of outcome was performed using the Kaplan-Meier method. Correlations were calculated between clinical-pathological variables. RESULTS: One hundred sixty-three patients underwent 198 liver resections for colorectal metastases: 26 major hepatectomies, 65 minor anatomical resections, 78 non-anatomical resections, as well as 29 combinations of minor anatomical and non-anatomical procedures. Overall 1-, 3-, and 5-year survival was 93%, 62%, and 40%, respectively. Patients with repeated liver resections had a 5-year survival of 27%. Interestingly, large dissection areas were associated with a significant reduction of the 5-year survival rate (33%). Five-year survival after major hepatectomy was not significantly reduced. CONCLUSION: For colorectal liver metastases, minor resections offer a prolonged survival compared to major hepatectomies. As patients with stage IV colorectal disease are candidates for repeat resections, preservation of hepatic parenchyma is of increasing importance in the setting of multi-modal and repeated therapy approaches.

Hepatic arterial infusion of bevacizumab in combination with oxaliplatin reduces tumor growth in a rat model of colorectal liver metastases.

Unresectable colorectal liver metastases are commonly treated with systemic chemotherapy (SCT). Clinical studies on the effect of additional systemic application of bevacizumab (BE), a monoclonal antibody directed against vascular endothelial growth factor, to SCT showed a slight increase of patient survival. Herein, we studied in a rat model of colorectal liver metastasis whether a locoregional application of oxaliplatin (OX) and BE via hepatic arterial infusion (HAI) is more effective to inhibit metastatic growth compared to systemic drug application. Ten days after implantation of CC531 colorectal cancer cells into the left liver lobe of WAG/Rij rats, animals underwent either HAI or systemic intravenous application of BE (5 mg/kg body weight), OX (85 mg/m(2) body surface) or a combination of both. Sham-treated animals received saline and served as controls. Tumor volume was measured at days 10 and 13 using three dimensional ultrasound. At day 13 tumor tissue was analyzed histologically and immunohistochemically. Systemic application of OX, BE or their combination did not affect tumor volume when compared to controls. In contrast, HAI of BE and particularly the combination of BE and OX significantly reduced tumor volume. In the tumor tissue this was associated with a decrease of vascularization and cell proliferation as well as an increase of cell apoptosis, as indicated by a decreased number of PECAM-1- and PCNA-positive cells and an increased number of cleaved caspase-3-positive cells. Locoregional administration of BE, particularly in combination with OX, enhances the inhibitory effect on hepatic metastatic growth compared to systemic application of the drugs.

Torquated giant appendix epiploica mimicking intraperitoneal liposarcoma: report of a case.

A 49-year-old woman presented with acute abdominal pain in the right iliac fossa in our emergency department. Pain was abrupt in onset and severely colicky in nature. Abnormal laboratory values included a C-reactive protein of 75 mg/L and a CA-125 of 70.3 U/mL. White blood cell count was normal. Abdominal computed tomography (CT) scan revealed an inhomogeneous mass of 9.5 x 3.5 x 5.5 cm in diameter close to the appendix vermiformis and the sigmoid colon. Because of the clinical symptoms of an acute abdomen an explorative laparotomy was performed. Intraoperatively a pedunculated tumor beginning at the serosa of the sigmoid colon was found. The appendix was unremarkable. The macroscopic aspect as well as the backtable incision of the tumor was suspicious of an intraperitoneal liposarcoma. Rapid section and histopathologic examination revealed necrotic fat tissue without any malignancy. The patient was discharged from the hospital 7 days after the operation with normal laboratory parameters and without further complication. When epiploic appendagitis is evident as a big tumor mass in addition to clinical symptoms of an acute abdomen and elevated tumor markers, surgical exploration is mandatory.

Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases.

AIM: To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer (CRC) patients. METHODS: Using Real Time-PCR, enzyme-linked immunosorbent assay, Western Blots and immunohistochemistry, we have analyzed the expression of CCL20, CCR6 and proliferation marker Ki-67 in colorectal liver metastasis (CRLM) specimens from stage IV CRC patients who received preoperative FOLFOX chemotherapy (n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery (n = 29). RESULTS: Of the 53 patients who received FOLFOX, time to liver surgery was ≤ 1 mo in 14 patients, ≤ 1 year in 22 patients and > 1 year in 17 patients, respectively. In addition, we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups. Both CCL20 and CCR6 mRNA and protein expression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ≤ 12 mo before liver surgery (P < 0.001) in comparison to patients who did not undergo FOLFOX treatment. Further, proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treatment. CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy. CONCLUSION: This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.

The nightknife©: evaluation of efficiency and quality of bipolar vessel sealing.

BACKGROUND: Nightknife(©) is a novel reusable bipolar vessel sealing device. In the present study we analyzed its efficiency and quality of vessel sealing in comparison to a standard instrument (LigaSure™). MATERIALS AND METHODS: Mesenteric veins and arteries of 5 Swabian-Hall pigs were sealed by means of Nightknife and LigaSure. Thermal performance of both devices was assessed by dynamic thermography. Analysis of the sealed vessels included the determination of seal failure rates and heat-associated macroscopic tissue appearance. RESULTS: The overall sealing rate of Nightknife was significantly higher than that of LigaSure (95.8% versus 87.0%; P=.012). This was associated with a more pronounced thermal spread (8.22±0.13 versus 7.12±0.10 mm; P=.012) and tissue desiccation (2.15±0.06 versus 1.86±0.07; P=.003). Moreover, sealing time (12.30±0.17 versus 7.72±0.17 seconds; P=.038) and tissue temperature (93.73°C±0.69°C versus 66.71°C±2.18°C; P=.001) were significantly higher with the use of Nightknife. Logistic regression analysis revealed that the degree of tissue desiccation correlated with the overall sealing success. CONCLUSION: Nightknife is as appropriate as LigaSure for the successful sealing of mesenteric vessels despite significant differences in tissue alterations and sealing time between the two devices.

Delayed gastric emptying after pancreaticoduodenectomy: influence of the orthotopic technique of reconstruction and intestinal motilin receptor expression.

BACKGROUND: Delayed gastric emptying (DGE) is still a common postoperative complication after pancreaticoduodenectomy (PD). Because different reconstruction techniques after PD and the influence of motilin receptor expression are controversially discussed, the present study analyzed the influence of a total orthotopic reconstruction technique on DGE after PD. METHODS: Data from patients undergoing PD and reconstruction using a total orthotopic technique were reviewed, and correlations between DGE and clinico-pathological variables were analyzed. Motilin receptor expression was measured within the duodenum, jejunum, and terminal ileum. RESULTS: Three hundred seven patients received orthotopic reconstruction using a single jejunal loop. DGE grade B or C could be observed in 16.6% of the patients. DGE was significantly associated with the severity of a postoperative pancreatic fistula, the need for a reoperation, wound infections, and vascular complications. Furthermore, these parameters correlated significantly with the grade of DGE. The density of motilin receptor expression decreased significantly behind the duodenum in aboral direction. CONCLUSIONS: The orthotopic reconstruction after PD is the shortest distance without resection of a jejunal segment, preserves the greatest length of jejunum and thus the highest density of motilin receptors, and should therefore be recommended to reduce the incidence of DGE after PD.

Triclosan-coated sutures reduce wound infections after hepatobiliary surgery--a prospective non-randomized clinical pathway driven study.

OBJECTIVES: Wound infections after abdominal surgery are still frequent types of nosocomial infections. Suture materials might serve as a vehicle for mechanical transport of bacteria into the surgical wound. To reduce bacterial adherence to surgical sutures, triclosan-coated polyglactin 910 suture materials with antiseptic activity (Vicryl plus®) were developed. The aim of this prospective non-randomized clinical pathway driven study was to ascertain if the use of Vicryl plus® reduced the number of wound infections after transverse laparotomy. PATIENTS AND METHODS: Between October 2003 and October 2007, 839 operations were performed using a transverse abdominal incision. In the first time period, a PDSII® loop suture was used for abdominal wall closure. In the second time period, we used Vicryl plus®. Risk factors were collected prospectively to compare the two groups. RESULTS: Using a PDSII® loop suture for abdominal wall closure in the first time period, 9.2% of the patients developed wound infections. In the second time period, using Vicryl plus®, the number of wound infections decreased to 4.3% (p < 0,005). Both groups were comparable regarding risk factors despite no other changes in protocols of patient care. CONCLUSION: Antiseptic-coated loop Vicryl suture for abdominal wall closure can be superior to PDSII sutures in respect to the development of wound infections after a two-layered closure of transverse laparotomy.

Darbepoetin-alpha enhances hepatectomy-associated stimulation of colorectal liver metastatic growth.

BACKGROUND: Liver insufficiency after major hepatectomy still represents a serious challenge in liver surgery. Although some previous studies indicate that erythropoietin (EPO) and its analogue darbepoetin-alpha (DPO) may improve liver function and liver regeneration, little is known on their effect on tumor growth after hepatectomy. Because EPO may promote tumor progression, we herein studied the effect of DPO on tumor growth after major hepatectomy. METHODS: CT26.WT colorectal cancer cells were implanted into the left liver lobe of BALB/c mice. Animals underwent 50% hepatectomy (Phx) and received 10 microg/kg DPO-treatment. Additional Phx animals received only saline treatment. Nonhepatectomized animals with DPO-treatment or saline treatment served as controls. One week after hepatectomy angiogenic blood vessel formation, leukocyte-endothelial cell interaction, tumor cell proliferation, apoptotic cell death, and tumor growth were studied using intravital fluorescence microscopy, histology, Immunohistochemistry, and Western blot analysis. RESULTS: Phx significantly enhanced the growth of liver metastases. This was associated with an increase of tumor capillary density and tumor cell proliferation. In nonhepatectomized animals, DPO only slightly affected metastatic growth. In hepatectomized animals, however, DPO significantly enhanced the Phx-induced stimulation of tumor growth. This was associated with an increased tumor capillary density, a decreased leukocyte-endothelial cell interaction, and a reduced cleaved caspase-3 expression of the CT26.WT cells. CONCLUSIONS: : Our data indicate that DPO significantly enhances the hepatectomy-induced stimulation of colorectal liver metastatic growth by increasing neovascularization, suppressing intratumoral leukocyte recruitment, and reducing tumor cell apoptosis. Thus, EPOs may not be used in patients undergoing hepatectomy for malignant tumor resection.