Sarcopenic Obesity Promotes Recurrence in Patients Undergoing Resection for Colorectal Liver Metastases (CRLM).

BACKGROUND/AIM: Sarcopenia, is predictive of a worse outcome after resection for colorectal liver metastases (CRLM). Obesity leads to a metabolic double burden if sarcopenia is as present, prompting malignancy progression, known as sarcopenic obesity (SO). This study aimed to compare sarcopenia and SO in patients undergoing CRLM resection, to prognostic parameters. PATIENTS AND METHODS: The skeletal muscle index (SMI) defined sarcopenia using sex specific cut off values (48.4 cm2/m2 for females and 59.1 cm2/m2 for males) by calculating the preoperative muscle mass at the vertebral height L3 using OSIRIX DICOM viewer. SO was determined as sarcopenia in patients showing obesity, as shown via fat percentage measurements on the preoperative CT scan. Established prognostic parameters (KRAS status, TNM classification, inflammatory response) were evaluated against SMI and SO to assess their predictability for postoperative outcomes. RESULTS: A total of 251 patients (62% female, median age 68 years) were included. Sarcopenic patients showed a threefold higher risk for postoperative death as compared to non-sarcopenic patients (p=0.04). Prevalent SO increased this risk to fivefold (p=0.01) compared to non-sarcopenic patients. COX regression analysis revealed SO and KRAS positivity as independent prognostic factors for disease-free survival (SO: p=0.038; KRAS: p=0.041; TNM, tumor size, Charlson Comorbidity Index, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio all not significant). Patients risk of death in case of KRAS positivity and SO was seven times higher (p=0.03). CONCLUSION: There seems to be a benefit in merging data on mutational status and muscle wasting in patients with CRLM to facilitate an individual, patient-tailored approach.

Intraoperative reperfusion assessment of human pancreas allografts using hyperspectral imaging (HSI).

Background: The most common causes of early graft loss in pancreas transplantation are insufficient blood supply and leakage of the intestinal anastomosis. Therefore, it is critical to monitor graft perfusion and oxygenation during the early post-transplant period. The goal of our pilot study was to evaluate the utility of hyperspectral imaging (HSI) in monitoring the microcirculation of the graft and adequate perfusion of the intestinal anastomosis during pancreatic allotransplantation. Methods: We imaged pancreatic grafts and intestinal anastomosis in real-time in three consecutive, simultaneous pancreas-kidney transplantations using the TIVITA® HSI system. Further, the intraoperative oxygen saturation (StO2), tissue perfusion (near-infrared perfusion index, NIR), organ hemoglobin index (OHI), and tissue water index (TWI) were measured 15 minutes after reperfusion by HSI. Results: All pancreas grafts showed a high and homogeneous StO2 (92.6%±10.45%). Intraoperative HSI analysis of the intestinal anastomosis displayed significant differences of StO2 (graft duodenum 67.46%±5.60% vs. recipient jejunum: 75.93%±4.71%, P<0.001) and TWI {graft duodenum: 0.63±0.09 [I (Index)] vs. recipient jejunum: 0.72±0.09 [I], P<0.001}. NIR and OHI did not display remarkable differences {NIR duodenum: 0.68±0.06 [I] vs. NIR jejunum: 0.69±0.04 [I], P=0.747; OHI duodenum: 0.70±0.12 [I] vs. OHI jejunum: 0.68±0.13 [I], P=0.449}. All 3 patients had an uneventful postoperative course with one displaying a Banff 1a rejection which was responsive to steroid treatment. Conclusions: Our study shows that contact-free HSI has potential utility as a novel tool for real-time monitoring of human pancreatic grafts after reperfusion, which could improve the outcome of pancreas transplantation. Further investigations are required to determine the predictive value of intraoperative HSI imaging.

Hyperspectral Imaging (HSI) of Human Kidney Allografts.

OBJECTIVE: Aim of our study was to test a noninvasive HSI technique as an intraoperative real time assessment tool for deceased donor kidney quality and function in human kidney allotransplantation. SUMMARY OF BACKGROUND DATA: HSI is capable to deliver quantitative diagnostic information about tissue pathology, morphology, and composition, based on the spectral characteristics of the investigated tissue. Because tools for objective intraoperative graft viability and performance assessment are lacking, we applied this novel technique to human kidney transplantation. METHODS: Hyperspectral images of distinct components of kidney allografts (parenchyma, ureter) were acquired 15 and 45 minutes after reperfusion and subsequently analyzed using specialized HSI acquisition software capable to compute oxygen saturation levels (StO2), near infrared perfusion indices (NIR), organ hemoglobin indices, and tissue water indices of explored tissues. RESULTS: Seventeen kidney transplants were analyzed. Median recipient and donor age were 55 years. Cold ischemia time was 10.8 ±â€Š4.1 hours and anastomosis time was 35 ±â€Š7 minutes (mean ±â€Šstandard deviation). Two patients (11.8%) developed delayed graft function (DGF). cold ischemia time was significantly longer (18.6 ±â€Š1.6) in patients with DGF (P < 0.01). Kidneys with DGF furthermore displayed significant lower StO2 (P = 0.02) and NIR perfusion indices, 15 minutes after reperfusion (P < 0.01). Transplant ureters displayed a significant decrease of NIR perfusion with increased distance to the renal pelvis, identifying well and poor perfused segments. CONCLUSION: Intraoperative HSI is feasible and meaningful to predict DGF in renal allografts. Furthermore, it can be utilized for image guided surgery, providing information about tissue oxygenation, perfusion, hemoglobin concentration, and water concentration, hence allowing intraoperative viability assessment of the kidney parenchyma and the ureter.

A young woman from an Echinococcus-endemic area with progressive abdominal distension: a case report.

BACKGROUND: Cystic echinococcosis is a zoonotic infection caused by Echinococcus granulosus. This case report shows the difficulty in differential diagnosis in a patient with highly suspected hydatid disease. CASE PRESENTATION: A 29-year-old Chinese woman presented with progressive abdominal distension. Imaging results revealed a large multicystic tumor with typical features of hydatid disease. There was no clear relationship between the cystic tumor and the liver, which led to the assumption of primary extrahepatic cystic echinococcosis. After albendazole therapy was initiated, a laparotomy was performed and a huge ovarian cystadenoma was diagnosed. CONCLUSIONS: This case highlights the possible challenges of differential diagnosis in patients with suspicion of hydatid cysts.

Robotic assisted nephrectomy for living kidney donation (RANLD) with use of multiple locking clips or ligatures for renal vascular closure.

BACKGROUND: Robotic assisted nephrectomy for living donation (RANLD) is a rapid emerging surgical technique competing for supremacy with totally laparoscopic and laparoscopic hand assisted techniques. Opinions about the safety of specific techniques of vascular closure in minimally invasive living kidney donation are heterogeneous and may be different for laparoscopic and robotic assisted surgical techniques. METHODS: We retrospectively analyzed perioperative and short-term outcomes of our first (n=40) RANLD performed with the da Vinci Si surgical platform. Vascular closure of renal vessels was performed by either double clipping or a combination of clips and non-transfixing suture ligatures. RESULTS: RANLD almost quintupled in our center for the observed time period. A total of n=21 (52.5%) left and n=19 (47.5%) right kidneys were procured. Renal vessel sealing with two locking clips was performed in 18 cases (45%) Both, clips and non-transfixing ligatures were used in 22 cases (55%). Mean donor age was 53.075±11.68 years (range, 28-70). The average total operative time was 150.75±27.30 min. Right donor nephrectomy (139±22 min) was performed significantly faster than left (160.95±27.93 min, P=0.01). Warm ischemia time was similar for both vascular sealing techniques and did not differ between left and right nephrectomies. No conversion was necessary. Clavien-Dindo Grade ≤IIIb complications occurred in (n=5) 12.5%. Grade IV and V complications did not develop. In particular no hemorrhage occurred using multiple locking clips or suture ligatures for renal vascular closure. Mortality was 0%. Thirteen kidneys (32.5%) were transplanted across the AB0 barrier. CONCLUSIONS: RANLD is an emerging minimally invasive surgical technique which facilitates excellent perioperative and short-term outcomes also when using multiple locking clips or suture ligatures for renal vascular closure.

[Laparoscopic Left Hemihepatectoy Applying Intraoperative Indocyanine Green Fluorescence Detection Counter Perfusion Method for Visualization]. / Laparoskopische Hemihepatektomie links mit intraoperativer Indocyaningrün-Perfusionsbildgebung.

Intraoperative indocyanine green (ICG) fluorescence detection by the "counter perfusion method" is a useful tool to identify hepatic segments and intersegmental planes during anatomic liver resection. We report of a 54-year old patient with recurrent cholangitis due to Caroli disease, who underwent a laparoscopic hemihepatectomy. To determine the resection line and resection plane, we injected ICG intravenously after clamping/ligating the left hepatic artery and left portal vein. Before and during resection the liver was observed under visible light and under near-infrared (NIR) light. This method allowed for precise anatomical resection of non-perfused liver segments 2, 3 and 4.

Hyperspectral Imaging (HSI) in anatomic left liver resection.

INTRODUCTION: Anatomic liver resection is based on the description of functional segments, which rely on the organs arterial and portal venous blood supply. Vascular inflow control of the left liver is performed by occlusion of the left hepatic artery (LHA) and left portal vein (LPV). Depending on the quality of the parenchyma a sharp demarcation line (Cantlie Line) between segments IV and V/VIII can hence be detected. MATERIAL AND METHODS: TIVITA® is a novel contact free tool which facilitates non-invasive hyperspectral imaging (HSI) and near infrared spectroscopy (NIRS) for the assessment of tissue- oxygenation (StO2) and perfusion (NIR Perfusion). We hypothesized that this imaging modality might be practicable to identify the future resection plane after left vascular inflow occlusion in anatomic liver resection. PRESENTATION OF CASE: TIVITA ® is a viable tool for the identification of segments with reduced StO2 (inflow occlusion: 0.23 ±â€¯0.03 vs normal: 0.50 ±â€¯0.06) and NIR Perfusion (inflow occlusion: 0.02 ±â€¯0.04 vs normal: 0.47 ±â€¯0.06) and allows for a visual differentiation of well oxygenated, perfused (green) and low oxygenated, poorly perfused (blue) liver tissue in a patient undergoing left hemihepatectomy for hepatocellular carcinoma. CONCLUSION: Hyperspectral Imaging is an emerging optical technique with the potential to identify exact resection planes for anatomic liver resection based on the optically determined perfusion and oxygenation status of liver segments lined up for resection. This novel Hyperspectral Demarcation Technique (HSI DT) is non- contact, non-ionizing and non-invasive.

Evolution of laparoscopic liver surgery as standard procedure for HCC in cirrhosis?

Patients with hepatocellular carcinoma (HCC) in cirrhosis have an increased risk for postoperative complications including liver failure. However, there is some evidence that the use of laparoscopy markedly decreases this risk. Patients Between 2010 - 2015, a total of 21 laparoscopic liver resections were performed for HCC in Child-A cirrhosis at our center. Mean MELD score was 9 (6 - 12), and the mean LiMAx was 261 µg/h/kg (101 - 489). All resections were performed by conventional laparoscopy using 4 - 6 trocars. Liver parenchyma was transected using ultrasonic shears. Hilar occlusion was used on demand. In the earlier years, laparoscopic resections were performed occasionally and mainly if tumors were easily accessible. With increasing experience, currently most HCC in cirrhosis are resected laparoscopically. Likewise, 12 out of the 21 resections were performed within the last 12 months, including 2 anatomic left hemihepatectomies. Results Conversion rate, postoperative mortality, and operative revision rate were all 0 %. Four patients (19 %) developed mild complications Clavien-Dindo grade 1 or 2 (ascites, transfusion, pneumonia, renal impairment). One patient (4.8 %) developed a grade 3 event (bile leak, percutaneous drainage). All but 1 early patient underwent R0 resection (95 %). The mean duration of hospital stay was 10.5 days (5 - 21), and the mean duration of ICU stay was 1.8 days (1 - 7). No case of decompensation of liver cirrhosis was observed. In 1 case, a prolonged production of ascites evolved. Conclusion Even in patients with severely impaired liver function, no severe complications and especially no decompensation of cirrhosis was observed. Therefore, in accordance with other single center experiences, liver resection for HCC in cirrhosis should be performed preferentially by laparoscopy.

Metastasis-associated in colon cancer 1 is an independent prognostic biomarker for survival in Klatskin tumor patients.

UNLABELLED: Curative treatment of intrahepatic cholangiocarcinoma (ICC) and hilar cholangiocarcinoma (Klatskin tumors) is limited to surgical resection or orthotopic liver transplantation. However, not all patients benefit from a surgical approach and suffer from early tumor recurrence. Response to chemotherapy is generally poor and, until today, no targeted therapy could be established. Metastasis-associated in colon cancer 1 (MACC1) is a recently discovered regulator of the hepatocyte growth factor (HGF)/Met/mitogen-activated protein kinase pathway, which induces proliferation, migration, and invasion in cell culture, as well as metastasis in mice. MACC1 expression shows a significant correlation with Met expression in colon cancer tissue and is highly prognostic for occurrence of distant metastasis and survival in colon cancer patients. Thus, we aimed to measure the expression of MACC1, Met, and HGF messenger RNA in microdissected tumor tissue and corresponding normal liver tissue of 156 patients with Klatskin tumors (n = 76) and ICC (n = 80) using real-time quantitative reverse-transcriptase polymerase chain reaction. We used immunohistochemical staining to validate the results. MACC1 expression in tumor tissue of both tumor entities was significantly higher than in corresponding normal liver tissue (P < 0.001). Klatskin tumor patients with a history of tumor recurrence had significantly higher MACC1 expression than those without tumor recurrence (P = 0.005). Uni- und multivariate survival analysis showed that Klatskin tumor patients with high MACC1 had a significantly shorter overall (OS) and disease-free survival (DFS; P = 0.001 and P < 0.001, respectively). The multivariate analysis confirmed MACC1 to be an independent factor for overall survival in Klatskin tumor patients (hazard ratio: 2.777; 95% confidence interval: 1.389-5.555; P = 0.004). CONCLUSION: Our study identified MACC1 as a highly prognostic biomarker for OS and DFS in Klatskin tumor patients. MACC1 expression could become an important diagnostic tool and might be a candidate for targeted therapy.

Postoperative bile leakage inhibits liver regeneration after 70% hepatectomy in rats.

BACKGROUND: Postoperative bile leakage is a typical complication in liver surgery. The influence of small bile leakage and concomitant bile peritonitis on the regenerative capacity of the liver remnant has not yet been investigated thoroughly. MATERIAL AND METHODS: Fifty-four rats were randomized in the following groups: Sham operation (Sh), 70% liver resection (LR), and 70% LR with simultaneous induction of a small bile leakage. Animals were euthanized 6, 24, 48, and 96 hr after surgery. Liver regeneration was measured by relative liver weight, mitotic index, Ki-67 immunohistochemistry, and BrdU labeling index. Liver function was evaluated by thromboplastin time, serum bilirubin, and albumin levels as well as indocyanine green plasma disappearance rate (ICG-PDR). The inflammatory response was characterized by assessment of the hepatic transcription of TNF-α, IL-6, and TGF-ß and the serum concentration of IL-1ß. In addition, myeloperoxidase (MPO) activity in liver tissue was measured. Transaminases and histological sections of the liver were used as markers for hepatocellular damage, and the bacterial concentration in different organs was quantified. RESULTS: With a small bile leakage, mitotic index was reduced by 89% ( p < .05) and the number of Ki-67 positive hepatocytes was reduced by 92% ( p < .05) 24 hr after LR. Likewise, the ICG-PDR dropped by 57% ( p < .05). No differences in liver histology were observed between the groups. With bile leakage, the postoperative transcription of cytokines was markedly higher. A bacterial superinfection could be excluded. CONCLUSION: Small intraabdominal bile leakage can suppress liver function and impair the regenerative capacity of the liver.

Curcumin attenuates oxidative stress and inflammatory response in the early phase after partial hepatectomy with simultaneous intraabdominal infection in rats.

BACKGROUND: Curcumin is a nontoxic, hepatoprotective antioxidant. It has been shown to efficiently scavenge oxygen free radicals, increase intracellular glutathione concentrations, and prevent lipid peroxidation in rat hepatocytes. Moreover, it has strong anti-inflammatory effects. In the present study we assessed its effect in a model of liver regeneration impaired by bacterial infections. MATERIAL AND METHODS: Male Sprague-Dawley rats underwent sham operation, cecal ligation and puncture (CLP), synchronous partial hepatectomy (PH), and CLP or synchronous PH+CLP with perioperative application of curcumin (100 mg per kg bodyweight per d) 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver function was analyzed by measuring the serum albumin, serum bilirubin, and bile production. The local inflammatory response in the liver tissue was evaluated by quantification of TNF-alpha, IL-6 mRNA, and quantification of IL-1beta by ELISA. In addition, hepatic concentrations of reduced glutathione (GSH) and the oxidized disulfide dimer of glutathione (GSSG) were measured for determination of the redox state. RESULTS: After simultaneous PH+CLP curcumin significantly reduced the expression of TNF-alpha and IL-6 mRNA in the liver tissue. The IL-1beta concentration in the liver was also slightly, but not significantly, lower in the curcumin group. A severe depletion of hepatic glutathione was found in the PH+CLP group. This was reversed by curcumin application, after which the GSH to GSSG ratio increased markedly. The hepatocellular damage, measured by ALT liberation, was significantly lower in the curcumin treated group. The relative liver weight in the curcumin group was significantly higher 24 h after PH+CLP. However, hepatocellular proliferation parameters were not significantly improved by antioxidative treatment with curcumin. Only the Ki-67 index was slightly higher in the curcumin treated PH+CLP group (14+/-3%) than in the untreated PH+CLP group (7%+/-3%). The hepatocyte density was significantly lower in the curcumin group than in the corresponding untreated group. CONCLUSION: In the present model, curcumin revealed significant hepatoprotective effects with stabilization of redox state, reduced liberation of liver enzymes, and attenuated expression of pro-inflammatory cytokines. However, the hepatocellular proliferation was not significantly influenced.

Synergistic effect of erythropoietin but not G-CSF in combination with curcumin on impaired liver regeneration in rats.

INTRODUCTION: The effect of erythropoietin (Epo) and granulocyte colony-stimulating factor (G-CSF) alone or in combination with the hepatoprotective antioxidant curcumin (Cur) was evaluated in a model of delayed liver regeneration. MATERIALS AND METHODS: Sprague Dawley rats underwent 70% liver resection with simultaneous cecal ligation and puncture and were randomised to five groups: no treatment, G-CSF (100 microg/kg), Epo (1,000 IU/kg), each alone or in combination with Cur (100mg/kg). Twenty-four hours after surgery, blood and tissue samples were collected. Markers of liver regeneration (liver weight, mitotic index, Ki-67 index), function (bilirubin, bile flow) and hepatocellular damage (liver enzymes, histomorphology) were determined. In addition, cytokine expression and hepatic glutathione concentrations were measured. RESULTS: Liver regeneration was not improved by G-CSF or Epo monotherapy. Epo more effectively increased liver weight and regeneration markers, but the difference was not significant. Whereas liver regeneration was slightly inhibited in the G-CSF plus Cur group, Epo plus Cur significantly improved liver regeneration. This was accompanied by reduced oxidative stress. Liver function and the expression of pro-inflammatory cytokines were comparable in all treatment groups. CONCLUSION: In the present model, Epo, at a relatively low dosage, did not improve liver regeneration. However, the combination of Epo and Cur showed a synergistic effect with highly significant stimulation of liver regeneration.