Patrick Hamid Alizai

Sarcopenia, obesity and sarcopenic obesity: effects on liver function and volume in patients scheduled for major liver resection

Sarcopenia, obesity and sarcopenic obesity have been linked to impaired outcome after liver surgery. Preoperative liver function of sarcopenic, obese and sarcopenic‐obese patients might be reduced, possibly leading to more post‐operative morbidity. The aim of this study was to explore whether liver function and volume were influenced by body composition in patients undergoing liver resection.

Extended Distal Pancreatectomy with En Bloc Resection of the Celiac Axis for Locally Advanced Pancreatic Cancer: A Case Report and Review of the Literature

Due to a lack of early symptoms, pancreatic cancers of the body and tail are discovered mostly at advanced stages. These locally advanced cancers often involve the celiac axis or the common hepatic artery and are therefore declared unresectable. The extended distal pancreatectomy with en bloc resection of the celiac artery may offer a chance of complete resection. We present the case of a 48-year-old female with pancreatic body cancer invading the celiac axis. The patient underwent laparoscopy to exclude hepatic and peritoneal metastasis. Subsequently, a selective embolization of the common hepatic artery was performed to enlarge arterial flow to the hepatobiliary system and the stomach via the pancreatoduodenal arcades from the superior mesenteric artery. Fifteen days after embolization, the extended distal pancreatectomy with splenectomy and en bloc resection of the celiac axis was carried out. The postoperative course was uneventful, and complete tumor resection was achieved. This case report and a review of the literature show the feasibility and safety of the extended distal pancreatectomy with en bloc resection of the celiac axis. A preoperative embolization of the celiac axis may avoid ischemia-related complications of the stomach or the liver.

Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model.

Background: Liver regeneration requires the formation of new blood vessels. Endothelial cell proliferation is stimulated by vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2. The aim of this study was to investigate VEGFR-2 expression in vivo during liver regeneration after partial hepatectomy (PHx). Methods: Transgenic VEGFR-2-luc mice were used in which the luciferase reporter gene was under control of the VEGFR-2 promoter. Following 2/3 PHx, the mice underwent in vivo bioluminescence imaging until the 14th postoperative day. Additionally, liver tissue was analyzed by immunohistochemistry, in vitro luminescence assays, and quantitative RT-PCR. Results: In vivo bioluminescence imaging showed a significant increase in VEGFR-2 promoter activity after PHx. Maximum signal was recorded on the 3rd day; 8 days postoperatively the signal intensity decreased significantly. On the 14th day, bioluminescence signal reached almost baseline levels. Immunohistochemistry, quantitative RT-PCR, and in vitro luminescence confirmed a significant increase on the 3rd day following resection. The mRNA expression of VEGFR-2 was significantly higher on day 3 than preoperatively as well as on day 8. Conclusion: In vivo bioluminescence imaging with transgenic VEGFR-2-luc mice is feasible and provides a convenient model for noninvasively studying VEGFR-2 expression during liver regeneration. This may facilitate further experiments with modulation of angiogenesis by different substances.

Biomechanical analyses of prosthetic mesh repair in a hiatal hernia model.

Recurrence rate of hiatal hernia can be reduced with prosthetic mesh repair; however, type and shape of the mesh are still a matter of controversy. The purpose of this study was to investigate the biomechanical properties of four conventional meshes: pure polypropylene mesh (PP-P), polypropylene/poliglecaprone mesh (PP-U), polyvinylidenefluoride/polypropylene mesh (PVDF-I), and pure polyvinylidenefluoride mesh (PVDF-S). Meshes were tested either in warp direction (parallel to production direction) or perpendicular to the warp direction. A Zwick testing machine was used to measure elasticity and effective porosity of the textile probes. Stretching of the meshes in warp direction required forces that were up to 85-fold higher than the same elongation in perpendicular direction. Stretch stress led to loss of effective porosity in most meshes, except for PVDF-S. Biomechanical impact of the mesh was additionally evaluated in a hiatal hernia model. The different meshes were used either as rectangular patches or as circular meshes. Circular meshes led to a significant reinforcement of the hiatus, largely unaffected by the orientation of the warp fibers. In contrast, rectangular meshes provided a significant reinforcement only when warp fibers ran perpendicular to the crura. Anisotropic elasticity of prosthetic meshes should therefore be considered in hiatal closure with rectangular patches.

Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment

Superparamagnetic iron oxide nanoparticles (SPION) may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation) of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the efficiency of the magnetic field traps can be enhanced by 38-fold for prostate and 8-fold for esophageal cancer. Therefore, our approach of endoscopic targeting is an improvement of the magnetic drug-targeting setups for SPION tumor therapy as it holds the possibility of reaching tumors inside the body in a minimal-invasive way. Future animal experiments must prove these findings in vivo.

Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation

BACKGROUND The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation. METHODS Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis (MiS): MiS <30% (n=27), MiS 30%-60% (n=41) and MiS >60% (n=26). The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction (EAD) and primary nonfunction (PNF). RESULTS The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF, one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group. CONCLUSION Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.

Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases

Background In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative stratification algorithms it is still debated which patients benefit most from surgical treatment. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a promising biomarker for distinct clinical conditions. Here, we examined a potential role of suPAR as a biomarker in patients undergoing resection of CRLM. Results Correlating with upregulated uPAR tissue expression in resected metastases, serum concentrations of suPAR were significantly elevated in CRLM patients compared to healthy controls. Importantly, patients with preoperative suPAR serum levels above the identified ideal cut-off value of 4.83 ng/ml showed a significantly reduced overall survival after resection of CRLM, both in right- and left-sided primary CRC. Moreover, multivariate Cox regression analysis revealed preoperative suPAR serum levels as a prognostic factor for mortality. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury (AKI) after CRLM resection, correlating with a longer postoperative hospitalization. Conclusion SuPAR represents a promising novel biomarker in CRLM patients that might help to guide preoperative treatment decisions regarding patients’ outcome and to identify patients particularly susceptible to AKI. Methods Expression levels of uPAR were analyzed in CRLM tissue using RT-PCR and immunohistochemistry. SuPAR serum levels were measured by ELISA in 104 CRC patients undergoing hepatic resection for CRLM and 50 healthy controls.

Impact of liver volume and liver function on posthepatectomy liver failure after portal vein embolization– A multivariable cohort analysis

Background Liver failure remains a life-threatening complication after liver resection, and is difficult to predict preoperatively. This retrospective cohort study evaluated different preoperative factors in regard to their impact on posthepatectomy liver failure (PHLF) after extended liver resection and previous portal vein embolization (PVE). Methods Patient characteristics, liver function and liver volumes of patients undergoing PVE and subsequent liver resection were analyzed. Liver function was determined by the LiMAx test (enzymatic capacity of cytochrome P450 1A2). Factors associated with the primary end point PHLF (according to ISGLS definition) were identified through multivariable analysis. Secondary end points were 30-day mortality and morbidity. Results 95 patients received PVE, of which 64 patients underwent major liver resection. PHLF occurred in 7 patients (11%). Calculated postoperative liver function was significantly lower in patients with PHLF than in patients without PHLF (67 vs. 109 μg/kg/h; p = 0.01). Other factors associated with PHLF by univariable analysis were age, future liver remnant, MELD score, ASA score, renal insufficiency and heart insufficiency. By multivariable analysis, future liver remnant was the only factor significantly associated with PHLF (p = 0.03). Mortality and morbidity rates were 4.7% and 29.7% respectively. Conclusion Future liver remnant is the only preoperative factor with a significant impact on PHLF. Assessment of preoperative liver function may additionally help identify patients at risk for PHLF.

Incisional Hernia Repair of Medium- and Large-Sized Defects: Laparoscopic IPOM Versus Open SUBLAY Technique

Abstract Background: Small incisional hernias can be repaired laparoscopically with low morbidity and reasonable recurrence rates. The aim of this study was to compare laparoscopic with open technique in medium- and large-sized defects regarding postoperative complications and recurrence rates. Methods: Between 2012 and 2016, 102 patients with medium- or large-sized defects according to EHS classification underwent incisional hernia repair. Patients’ characteristics, hernia size and postoperative complications were prospectively recorded. In October 2016, eligible patients were assessed for recurrence. Results: About 31 patients underwent laparoscopic IPOM and 71 patients open SUBLAY repair. Morbidity rate was significantly lower in IPOM group than in SUBLAY group (19% versus 41%; p = .028). Postoperative complications according to Clavien–Dindo classification were significantly lower in the IPOM group (p = .021). Duration of surgery (88 versus 114 min; p = .009) and length of hospital stay (five versus eight days; p < .001) were significantly shorter for IPOM than for SUBLAY. 71 patients were available for follow-up. Recurrence rates showed no significant difference between study groups (13% versus 7%, p = .508). Conclusions: Laparoscopic repair in medium- and large-sized defects is a feasible and safe approach. IPOM compared to SUBLAY significantly reduces postoperative complications and hospital stay; recurrence rates are comparable.