Portocaval shunt can optimize transhepatic flow following extended hepatectomy: a short-term study in a porcine model.

The aim of this study was to evaluate whether the portocaval shunt (PCS) corrects these unwanted changes in transhepatic flow after extended hepatectomy (EH). Forty female Landrace pigs were divided into two main groups: (A) EH (75%) and (B) no EH. Group A was divided into 3 subgroups: (A1) EH without PCS; (A2) EH with side-to-side PCS; and (A3) EH with end-to-side PCS. Group B was divided into 2 subgroups: (B1) side-to-side PCS and (B2) end-to-side PCS. HAF, PVF, and PVP were measured in each animal before and after the surgical procedure. EH increased the PVF/100 g (173%, p < 0.001) and PVP (68%, p < 0.001) but reduced the HAF/100 g (22%, p = 0.819). Following EH, side-to-side PCS reduced the increased PVF (78%, p < 0.001) and PVP (38%, p = 0.001). Without EH, side-to-side PCS reduced the PVF/100 g (68%, p < 0.001) and PVP (12%, p = 0.237). PVP was reduced by end-to-side PCS following EH by 48% (p < 0.001) and without EH by 21% (p = 0.075). PCS can decrease and correct the elevated PVP and PVF/100 g after EH to close to the normal values prior to resection. The decreased HAF/100 g in the remnant liver following EH is increased and corrected through PCS.

Simultaneous Serial Transverse Enteroplasty (STEP) in Size Mismatch Small Bowel Transplantations.

BACKGROUND: Small bowel transplantation (SBTX) in children receiving larger grafts from adults can be challenging because of size mismatch. The aim of the present study was to assess whether a simultaneous serial transverse enteroplasty (STEP) can address the problem of size mismatch. METHODS: Three different size ratio groups between donors and recipients were compared in a porcine model with a 14-day follow-up. The groups were size matched, size mismatched (1:3.8 weight ratio), and size mismatched + STEP (each n = 8). RESULTS: It was technically feasible to simultaneously perform a STEP and SBTX of a mismatched intestinal segment. The postoperative clinical course was uneventful. No signs of bleeding, leakage, stenosis, or ileus were observed and the intestinal segment was well perfused at relaparotomy. Body weight decreased in all groups, but the percentage decrease was lowest in the mismatched + STEP group. Vital enterocyte masses were similar in all the groups (citrulline levels) and the nutritional status was best in the STEP group (transferrin levels, p = 0.04). CONCLUSIONS: We have demonstrated that a simultaneous STEP and SBTX procedure is technically feasible and clinically useful in overcoming the challenges associated with size mismatched SBTX. Our short-term findings justify further investigation in a larger series to elucidate the long-term outcomes of this procedure.

ARFI shear-wave elastography with simulation of acute urinary tract obstruction in an ex vivo porcine kidney model.

METHODS: A total of 20 heparinized pig kidneys were investigated at 10 intrapelvic hydrostatic pressure steps (0-90 mmHg). SWE (ARFI; Virtual TouchTM IQ, Siemens) measurements were taken at three different measuring regions and in two measuring sequences using a linear ultrasonography probe (9L4, Siemens). Median values of 10 shear-wave speed (SWS) measurements were calculated for each pressure step. Logarithmic transformed median SWS values were analyzed in a linear mixed model. RESULTS: SWS increased significantly with increasing intrapelvic pressure. Median SWS for all kidneys in both measuring sequences and all measuring regions was 1.47 m/s (interquartile range [IQR], 0.38 m/s) at 0 mmHg, 1.94 m/s (IQR, 0.42 m/s) at 30 mmHg, 2.07 m/s (IQR, 0.43 m/s) at 60 mmHg, 2.24 m/s (IQR, 0.49 m/s) at 90 mmHg. The correlation between pelvic pressure increase and median SWS values for the central parenchyma was significantly higher compared with the peripheral parenchyma. CONCLUSION: Acutely increased renal pelvic pressure correlates with increasing SWS values in ARFI elastography in an ex vivo porcine kidney model.

The optimal intestinal segment length for experimental size-mismatched intestinal transplantation: Defining the maximum length with the lowest blood flow needs in a porcine model.

Transplanted Intestinal Segments (IS) must match the perfusion capacities of the recipient. This can be challenging during a size-mismatched SBTX. In this study, we defined the maximum IS length with lowest blood flow needs in a porcine model by evaluating the physiological perfusion rates of different IS lengths. Blood flow in the SMA, aorta segment four, and general circulatory parameters were monitored before and after sequential intestinal resection. IS lengths of 30 cm, 60 cm, 120 cm, and 300 cm (n = 8 each) were compared. The IS blood flow requirements increased with IS length (30 cm: 19.5 ± 3.4 mL/min; 60 cm: 16.9 ± 6.7 mL/min; 120 cm: 34.9 ± 8.5 mL/min; 300 cm: 62.9 ± 11.6 mL/min). Absolute IS blood flow (P = .004), percentage IS blood flow uptake from the SMA (P = .001), and percentage IS blood flow uptake from the aorta (P = .005) increased significantly between 60 cm and 120 cm. We concluded that 60 cm was the maximum IS length before blood flow demands significantly increased in a porcine model.

Indocyanine green fluorescence imaging in hepatobiliary surgery.

Indocyanine green (ICG) is a fluorescent dye that has been widely used for fluorescence imaging during hepatobiliary surgery. ICG is injected intravenously, selectively taken up by the liver, and then secreted into the bile. The catabolism and fluorescence properties of ICG permit a wide range of visualization methods in hepatobiliary surgery. We have characterized the applications of ICG during hepatobiliary surgery into: 1) liver mapping, 2) cholangiography, 3) tumor visualization, and 4) partial liver graft evaluation. In this literature review, we summarize the current understanding of ICG use during hepatobiliary surgery. Intra-operative ICG fluorescence imaging is a safe, simple, and feasible method that improves the visualization of hepatobiliary anatomy and liver tumors. Intravenous administration of ICG is not toxic and avoids the drawbacks of conventional imaging. In addition, it reduces post-operative complications without any known side effects. ICG fluorescence imaging provides a safe and reliable contrast for extra-hepatic cholangiography when detecting intra-hepatic bile leakage following liver resection. In addition, liver tumors can be visualized and well-differentiated hepatocellular carcinoma tumors can be accurately identified. Moreover, vascular reconstruction and outflow can be evaluated following partial liver transplantation. However, since tissue penetration is limited to 5-10mm, deeper tissue cannot be visualized using this method. Many instances of false positive or negative results have been reported, therefore further characterization is required.

Methylisoindigo preferentially kills cancer stem cells by interfering cell metabolism via inhibition of LKB1 and activation of AMPK in PDACs.

Pancreatic ductal adenocarcinoma (PDAC) clinically has a very poor prognosis. No small molecule is available to reliably achieve cures. Meisoindigo is chemically related to the natural product indirubin and showed substantial efficiency in clinical chemotherapy for CML in China. However, its effect on PDAC is still unknown. Our results showed strong anti-proliferation effect of meisoindigo on gemcitabine-resistant PDACs. Using a recently established primary PDAC cell line, called Jopaca-1 with a larger CSCs population as model, we observed a reduction of CD133+ and ESA+/CD44+/CD24+ populations upon treatment and concomitantly a decreased expression of CSC-associated genes, and reduced cellular mobility and sphere formation. Investigating basic cellular metabolic responses, we detected lower oxygen consumption and glucose uptake, while intracellular ROS levels increased. This was effectively neutralized by the addition of antioxidants, indicating an essential role of the cellular redox balance. Further analysis on energy metabolism related signaling revealed that meisoindigo inhibited LKB1, but activated AMPK. Both of them were involved in cellular apoptosis. Additional in situ hybridization in tissue sections of PDAC patients reproducibly demonstrated co-expression and -localization of LKB1 and CD133 in malignant areas. Finally, we detected that CD133+/CD44+ were more vulnerable to meisoindigo, which could be mimicked by LKB1 siRNAs. Our results provide the first evidence, to our knowledge, that LKB1 sustains the CSC population in PDACs and demonstrate a clear benefit of meisoindigo in treatment of gemcitabine-resistant cells. This novel mechanism may provide a promising new treatment option for PDAC.

Hepatic Hemodynamic Changes Following Stepwise Liver Resection.

AIM: Extended liver resection has increased during the last decades. However, hepatic hemodynamic changes after resection and the consequent complications like post hepatectomy liver failure are still a challenging issue. The aim of this study was to systematically evaluate the role of stepwise liver resection on hepatic hemodynamic changes. METHODS: To evaluate this effect we performed 25, 50, and 75 % sequential liver resections in 10 pigs. Before and after each resection, the hepatic artery flow and portal vein flow in relation to the remnant liver volume (RLV) as well as hepatic vascular pressures were measured and compared between the groups. RESULTS: Following sequential liver resection, the hepatic artery flow /100 g decreases and the portal vein flow increases up to 17 and 167 % following extended liver resection (75 %), respectively. Also, during stepwise liver resection, the portal vein pressure increases gradually up to 33 % following extended hepatectomy (75 %). CONCLUSION: Sequential decrease in the RLV decreases the hepatic artery flow /100 g and increases the portal vein flow /100 g and portal vein pressure. As the consequence, the liver goes under more poor-oxygenated blood supply and higher pressure. This may be one of the most important mechanisms of the post hepatectomy liver failure in case of extended liver resection.

Towards markerless navigation for percutaneous needle insertions.

PURPOSE: Percutaneous needle insertions are increasingly used for diagnosis and treatment of abdominal lesions. The challenging part of computed tomography (CT)-guided punctures is the transfer of the insertion trajectory planned in the CT image to the patient. Conventionally, this often results in several needle repositionings and control CT scans. To address this issue, several navigation systems for percutaneous needle insertions have been presented; however, none of them has thus far become widely accepted in clinical routine. Their benefit for the patient could not exceed the additional higher costs and the increased complexity in terms of bulky tracking systems and specialized markers for registration and tracking. METHODS: We present the first markerless and trackerless navigation concept for real-time patient localization and instrument guidance. It has specifically been designed to be integrated smoothly into the clinical workflow and does not require markers or an external tracking system. The main idea is the utilization of a range imaging device that allows for contactless and radiation-free acquisition of both range and color information used for patient localization and instrument guidance. RESULTS: A first feasibility study in phantom and porcine models yielded a median targeting accuracy of 6.9 and 19.4 mm, respectively. CONCLUSIONS: Although system performance remains to be improved for clinical use, expected advances in camera technology as well as consideration of respiratory motion and automation of the individual steps will make this approach an interesting alternative for guiding percutaneous needle insertions.

Significance of the Extent of Intestinal Resection on the Outcome of a Short-bowel Syndrome in a Porcine Model.

AIM OF THE STUDY: Insufficient data are available to determine the most suitable extent of intestinal resection required to induce short-bowel syndrome (SBS) in pigs. This study aimed to compare the three main SBS-models published. METHODS: A 75%, 90%, or 100% mid-intestinal resection was performed in groups of n = 5 pigs each. Clinical (body weight, stool consistency) and biochemical (serum eletrolytes, citrulline, albumin, prealbumin, and transferrin) parameters were determined daily, functional (D-xylose resorption) and histological (intestinal villus length) parameters were determined after 2 weeks. A t-test and ANOVA were used for statistical analysis. RESULTS: Only in the 100% group, we observed a persistent weight loss (13.6 ± 3.8%) and diarrhea, as well as a decrease in prealbumin-levels (41%) and transferrin levels (33%). Serum electrolytes remained stable in all groups during the observation period. Citrulline stabilized at different levels (100% group 13.9 ± 1.0 µmol/L; 90% group 18.8 ± 1.0 µmol/L; 75% group 26.3 ± 1.4 µmol/L; all p < .05). D-xylose resorption was lowest in the 100%, followed by 90% and 75% group (100% group 32.8 ± 4.9 mg/L; 90% group 50.0 ± 19.6 mg/L; 75% group 57.8 ± 8.8 mg/L; p = .393). Intestinal villus length decreased in all groups (100% group 11.0%; 90% group 14.0%; 75% group 19.1%). CONCLUSIONS: 75% intestinal resection is less suitable as an SBS model, as animals tend to recover remarkably. The 90% model is suitable for longer-term studies, as animals might survive longer due to partial compensation. Due to severe nutritional, biochemical, and physiological derangements, the 100% model can only be used for acute experiments and those immediately followed by small bowel transplantation.

Acute respiratory distress syndrome induction by pulmonary ischemia-reperfusion injury in large animal models.

Acute respiratory distress syndrome (ARDS) is a common critical pulmonary complication after esophagectomy and other thoracic surgeries (e.g., lung transplantation, pulmonary thromboendarterectomy). Direct pulmonary ischemia-reperfusion injury (PIRI) is known to play the main role in induction of ARDS in these cases. Large animal models are an appropriate choice for ARDS as well as PIRI study because of their physiological and anatomic similarities to the human body. With regard to large animal models, we reviewed different methods of inducing in situ direct PIRI and the commonly applied methods for diagnosing and monitoring ARDS or PIRI in an experimental research setting.