Effect of immunosuppressive medication on postoperative complications following abdominal surgery in Crohn's disease patients.

BACKGROUND: Immunosuppressants represent an effective pharmacological treatment for the remission and management of Crohn's disease (CD); however, it has not been well-defined if these medications are associated with an increased incidence of postoperative complications after intestinal surgery. This retrospective study evaluated the association between immunosuppressive treatment and complications following bowel resection in patients with CD. METHODS: A total of 426 patients with CD who underwent abdominal surgery between 2001 and 2018 were included in the study. The participants were divided into two groups. In the first group, patients were under immunosuppressive treatment at the time of surgical resection, while in the second group, patients had never received pharmacological therapy for CD before surgery. RESULTS: No statistically significant difference was found in the incidence of postoperative complications between the two groups. Double or triple immunosuppressive therapy was not associated with increased complications compared to monotherapy or no pharmacological treatment. Preoperative risk factors such as hypoalbuminemia, abscess, fistula, intestinal perforation, long duration of symptoms, and the intraoperative performance of more than one anastomosis were related to increased rates of postoperative complications. Factors affecting the occurrence of postoperative complications in the univariate analysis were included in the multivariate analysis using a stepwise logistic regression model, and these factors were also related to increased rates of postoperative surgical complications. CONCLUSION: Immunosuppressive therapy was not associated with increased rates of postoperative complications following bowel resection in patients with CD.

Volume-Function Analysis (LiMAx Test) in Patients with HCC and Cirrhosis Undergoing TACE-A Feasibility Study.

BACKGROUND: Transarterial chemoembolization (TACE) is an important therapy for hepatocellular carcinoma (HCC) in cirrhosis. In particular in advanced cirrhosis, post-TACE hepatic failure liver (PTHF) failure may develop. Currently, there is no standardization for the periinterventional risk assessment. The liver maximum capacity (LiMAx) test assesses the functional liver capacity, but has not been investigated in this setting. AIMS: The aim of this study was to prospectively evaluate periinterventional LiMAx and CT volumetry measurements in patients with cirrhosis and HCC undergoing repetitive TACE. METHODS: From 06/2016 to 11/2017, eleven patients with HCC and cirrhosis undergoing TACE were included. LiMAx measurements (n = 42) were conducted before and after each TACE. Laboratory parameters were correlated with the volume-function data. RESULTS: The median LiMAx levels before (276 ± 166 µg/kg/h) were slightly reduced after TACE (251 ± 122 µg/kg/h; p = 0.08). This corresponded to a median drop of 7.1%. Notably, there was a significant correlation between LiMAx levels before TACE and bilirubin (but not albumin nor albumin-bilirubin [ALBI] score) increase after TACE (p = 0.02, k = 0.56). Furthermore, a significantly higher increase in bilirubin in patients with LiMAx ≤ 150 µg/kg/h was observed (p = 0.011). LiMAx levels at different time points in single patients were similar (p = 0.2). CONCLUSION: In our prospective pilot study in patients with HCC and cirrhosis undergoing multiple TACE, robust and reliable LiMAx measurements were demonstrated. Lower LiMAx levels before TACE were associated with surrogate markers (bilirubin) of liver failure after TACE. Specific subgroups at high risk of PTHF should be investigated. This might facilitate the future development of strategies to prevent occurrence of PTHF.

Common variation in FAM155A is associated with diverticulitis but not diverticulosis.

Colonic diverticulosis is a very common condition. Many patients develop diverticulitis or other complications of diverticular disease. Recent genome-wide association studies (GWAS) consistently identified three major genetic susceptibility factors for both conditions, but did not discriminate diverticulititis and diverticulosis in particular due the limitations of registry-based approaches. Here, we aimed to confirm the role of the identified variants for diverticulosis and diverticulitis, respectively, within a well-phenotyped cohort of patients who underwent colonoscopy. Risk variants rs4662344 in Rho GTPase-activating protein 15 (ARHGAP15), rs7609897 in collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) and rs67153654 in family with sequence similarity 155 A (FAM155A) were genotyped in 1,332 patients. Diverticulosis was assessed by colonoscopy, and diverticulitis by imaging, clinical symptoms and inflammatory markers. Risk of diverticulosis and diverticulitis was analyzed in regression models adjusted for cofactors. Overall, the variant in FAM155A was associated with diverticulitis, but not diverticulosis, when controlling for age, BMI, alcohol consumption, and smoking status (ORadjusted 0.49 [95% CI 0.27-0.89], p = 0.002). Our results contribute to the assessment specific genetic variants identified in GWAS in the predisposition to the development of diverticulitis in patients with diverticulosis.

Predictive Power of Liver Maximum Function Capacity Test in Transjugular Intrahepatic Portosystemic Shunt Patients: A Pilot Study.

BACKGROUND: Transjugular intrahepatic shunt (TIPSS) is placed in patients with variceal bleeding, refractory ascites, and for other indications. Postprocedural liver function-associated complications (LFAC), including hepatic encephalopathy (HE) and liver failure, represent a major setback. Current methods to predict complications are insufficient. OBJECTIVES: We investigated in a pilot study of patients prior TIPSS placement whether the risk of LFAC correlates with the functional reserve of the liver, as assessed by liver maximum function capacity (LiMAx) test. METHODS: Prospectively we included patients prior TIPSS placement between June 2016 and November 2017 at Saarland University Medical Center. LiMAx was conducted before and after TIPSS placement. Patients with HE prior TIPSS, as well as other factors predisposing to HE, including concomitant sedative drugs, current bacterial infections and sepsis, were excluded. Overt HE (OHE), LiMAx, and laboratory values were assessed before and after TIPSS placement. Data were analyzed in multivariate regression and AUROC models. RESULTS: Mean age was 60 ± 8 years. Patients (n = 20) were mainly men (65%), and presented predominantly with Child-Pugh class B (90%). Indications for TIPSS were most commonly refractory ascites or recurrent variceal bleeding. In total, 40% of the patients developed LFAC after TIPSS placement. Expectedly, LiMAx decreased and serum bilirubin increased after TIPSS. LiMAx drop ≥20% was the only parameter predicting the development of LFAC after TIPSS in multivariate regression and AUROC analysis. CONCLUSIONS: In multivariate regression models and AUROC analysis, a drop in LiMAx predicted the development of LFAC after TIPSS placement. Additional larger studies assessing OHE and early liver failure separately are warranted.

A Variant of COL3A1 (rs3134646) Is Associated With Risk of Developing Diverticulosis in White Men.

BACKGROUND: Colonic diverticulosis is one of the most common gastroenterological disorders. Although diverticulosis is typically benign, many individuals develop diverticulitis or other aspects of diverticular disease. Diverticulosis is thought to stem from a complex interaction of environmental, dietary, and genetic factors; however, the contributing genetic factors remain unknown. OBJECTIVE: The aim of our present study was to determine the role of genetic variants within genes encoding for collagens of the connective tissue in diverticulosis. DESIGN: This was a transsectional genetic association study. SETTINGS: This study was conducted at three tertiary referral centers in Germany and Lithuania. PATIENTS: Single-nucleotide polymorphisms in COL3A1 (rs3134646, rs1800255) and COL1A1 (rs1800012) were genotyped in 422 patients with diverticulosis and 285 controls of white descent by using TaqMan assays. MAIN OUTCOME MEASURES: The association of colonoscopy-proven diverticulosis with genetic polymorphisms with herniations was assessed in multivariate models. RESULTS: The rs3134646, rs1800255, and rs1800012 variants were significantly associated with the risk of developing diverticulosis in the univariate model; however, these associations were not significant in the multivariate logistic regression analysis including additional nongenetic variables. When selectively analyzing sexes, the genotype AA (AA) in rs3134646 remained significantly associated with diverticulosis in men (OR, 1.82; 95% CI, 1.04-3.20; p = 0.04). LIMITATIONS: Because a candidate approach was used, additional relevant variants could be missed. Within our cohort of patients with diverticulosis, only a small proportion had diverticular disease and thus, we could not examine the variants in these subgroups. Functional studies, including the analysis of the involved collagens, are also warranted. CONCLUSIONS: Our study shows that a variant of COL3A1 (rs3134646) is associated with the risk of developing colonic diverticulosis in white men, whereas rs1800255 (COL3A1) and rs1800012 (COL1A1) were not associated with this condition after adjusting for confounding factors. Our data provide novel valuable insights in the genetic susceptibility to diverticulosis. See Video Abstract at http://links.lww.com/DCR/A504.

LiMAx Test Improves Diagnosis of Chemotherapy-Associated Liver Injury Before Resection of Colorectal Liver Metastases.

BACKGROUND: Chemotherapy of colorectal liver metastases (CLMs) prior to liver resection implies the risk of chemotherapy-associated liver injury, leading to increased postoperative morbidity and mortality OBJECTIVE: The aim of this study was to evaluate the LiMAx (liver maximum capacity) test for diagnosis of chemotherapy-associated liver injury. METHODS: This was a retrospective analysis of patients with CLMs, prior to liver resection. We performed preoperative assessment of liver function using biochemical parameters and the LiMAx test. The individual history of chemotherapy within 12 months, including regimen, number of cycles, and therapy-free interval were collected, and histopathological evaluation of tumor-free liver tissue was performed in resected patients. RESULTS: A total of 204 patients were included, of whom 127 (62%) had received previous chemotherapy. The LiMAx test was worse after chemotherapy (340 ± 95 vs. 391 ± 82 µg/kg/h; p < 0.001). Impaired LiMAx results (<315 µg/kg/h) were determined in 49% of patients after chemotherapy, and no effects of chemotherapy, liver steatosis or fibrosis on biochemical parameters were observed. LiMAx impairment was dependent on the number of oxaliplatin cycles, the therapy-free interval, and obesity in multivariate analysis. In addition, the LiMAx test was worse in patients with relevant steatosis, fibrosis and steatohepatitis. Patients with an impaired LiMAx showed sufficient regeneration during chemotherapy cessation when surgery was postponed (272 ± 57 - 348 ± 72 µg/kg/h; p = 0.003). CONCLUSION: The LiMAx test enables non-invasive preoperative diagnosis of chemotherapy-associated liver injury. Preoperative performance of the LiMAx test can augment surgical strategy and timing of surgery after previous chemotherapy, thus avoiding increased postoperative morbidity.

Preliminary study on liver function changes after trisectionectomy with versus without prior portal vein embolization.

PURPOSE: Post-hepatectomy liver failure (PHLF) is the major risk factor for mortality after hepatectomy. Preoperative planning of the future liver remnant volume reduces PHLF rates; however, future liver remnant function (FLR-F) might have an even stronger predictive value. In this preliminary study, we used a new method to calculate FLR-F by the LiMAx test and computer tomography-assisted volumetric-analysis to visualize liver function changes after portal vein embolization (PVE) before extended hepatectomy. METHODS: The subjects included patients undergoing extended right hepatectomy either directly (NO-PVE group) or after PVE (PVE group). Computed tomography (CT) scan and liver function tests (LiMAx) were done before PVE and preoperatively. FLR-F was calculated and correlated with the postoperative liver function. RESULTS: There were 12 patients in the NO-PVE group and 19 patients in the PVE group. FLR-F and postoperative liver function correlated significantly in both groups (p = 0.036, p = 0.011), although postoperative liver function was slightly overestimated, at 32 and 45 µg/kg/min, in the NO-PVE and PVE groups, respectively. LiMAx value did not change after PVE. CONCLUSIONS: Volume-function analysis using LiMAx and CT scan enables us to reliably predict early postoperative liver function. Global enzymatic liver function measured by the LiMAx test did not change after PVE, confirming that liver function distribution in the liver stays constant after PVE. An overestimation of FLR-F is needed to compensate for the intraoperative liver injury that occurs in patients undergoing extended hepatectomy.

Bovine pericardium for portal vein reconstruction in abdominal surgery: a surgical guide and first experiences in a single center.

BACKGROUND: Resection and reconstruction of infiltrated vessels achieve resectability of extended pancreatic tumors. The aim of the present study was to assess the feasibility of bovine pericardium as graft material for the individualised portal vein reconstruction and demonstrate a surgical technique for abdominal vein repair. METHODS: We performed a MEDLINE search to review the methods for complex abdominal vein reconstruction in the course of extended pancreatectomy. Moreover, clinical data of patients receiving portal vein reconstruction using a bovine pericardial patch at our institution were retrospectively analyzed. RESULTS: Based on the results of a review of the literature, autologous venous grafts using the internal jugular vein represent the most popular option for segmental portal vein reconstruction in case of impossible direct suture. At our center, segmental portal vein reconstruction with bovine pericardial patch in course of pancreatic surgery was performed in 4 patients. No case of vascular complications such as occlusion, segmental stenosis or thrombosis occurred. CONCLUSIONS: Our experience suggests a surgical procedure for an individual size-matched portal vein reconstruction using bovine pericardium. Although first results appear promising, prospective studies are required to objectively assess the patency of bovine pericardium compared with autologous and synthetic interposition grafts for portal vein reconstruction.

Factors influencing hypertrophy of the left lateral liver lobe after portal vein embolization.

PURPOSE: Portal vein embolization (PVE) before extended right hepatectomy leads to an increase of the future liver remnant (FLR) volume, but predictive factors for sufficient hypertrophy are still unclear. The purpose of this study was to investigate parameters influencing the growth of FLR. METHODS: Patients undergoing PVE prior hepatic resection were evaluated. PVE was done using polyvinyl alcohol particles only. Volumetric analysis was performed before embolization and before hepatectomy. Success of PVE was determined as percental growth of the future liver remnant. RESULTS: Seventy-seven patients were included, and three cohorts were formed according to the hypertrophy of FLR. FLR increased from 448.2 ± 187 to 475.5 ± 191 in the poor, from 315.3 ± 86 to 469.1 ± 142 in the moderate, and from 283.4 ± 68 to 400.4 ± 110 in the good hypertrophy group. More cases of recanalization of the portal vein were observed in patients with poor hypertrophy (p = 0.016). Small FLR before PVE predict higher growth of the FLR (p = 0.006). Duration between PVE and surgery differed significantly: 22 (poor) vs. 32 (good) days (p = 0.040). DISCUSSION: No recanalization, small initial FLR and longer time were assessed with better FLR hypertrophy. More sufficient PVE techniques and postponed hepatectomy might improve the outcome. Small initial FLR should not be a disclosure for curative hepatectomy.

Reliable assessment of liver function using LiMAx.

BACKGROUND: (13)C-liver function breath tests can facilitate the assessment of hepatic function in-vivo and may help surgeons to identify candidates for safe liver surgery. However, their acceptance into clinical practice is dependent on evaluation of technical efficacy and repeatability. The aims of this study were to evaluate the within-subject repeatability of the LiMAx (maximum liver function capacity) test in healthy individuals and in surgical patients to determine liver function in the perioperative workup. MATERIAL AND METHODS: The LiMAx test, which is based on intravenous injection of (13)C-methacetin at a dosage of 2 mg/kg body weight was performed in eighty-six healthy subjects to determine a reference range. Twenty-four subjects underwent repeat LiMAx testing the following day to assess within-subject repeatability. Twenty-one patients undergoing elective extra-abdominal surgery under general anesthesia (GA group) received pre- and post-operative examinations. RESULTS: The normal range of LiMAx was found to be 430 ± 86 µg/kg/h and revealed a one-sided cut-off value of 315 µg/kg/h. The intraclass correlation coefficient of the repeat LiMAx tests was 0.85 (95% confidence interval 0.69-0.93) in the control group and 0.81 (95% confidence interval 0.60-0.92) in the group of patients with GA. CONCLUSIONS: The LiMAx test shows excellent reproducibility in subjects with normal liver function. GA has no effect on test results.

Growth hormone/insulin-like growth factor 1 dynamics in adult living donor liver transplantation.

End-stage liver disease is accompanied by decreased serum levels of insulin-like growth factor 1 (IGF1) and inversely increased serum levels of growth hormone (GH). Previous reports have demonstrated rapid GH/IGF1 axis recovery after orthotopic liver transplantation. This study investigated the effect in an adult-to-adult living donor liver transplantation (LDLT) model and characterized GH/IGF1 alterations and liver regeneration in both donors and recipients. Sequential blood samples were prospectively collected from 30 donor-recipient pairs during the perioperative course of LDLT. A distinct set of biochemical parameters, including serum GH, serum IGF1, and standard liver blood tests, was analyzed at different time points (preoperatively and during 12 months of follow-up after surgery). Recipients showed significantly higher GH serum levels and lower IGF1 serum levels in comparison with donors before surgery and throughout the first postoperative days (PODs). The GH serum levels of recipients declined, whereas donor levels inversely increased during the early postoperative period to a normal range. Recipients' IGF1 serum levels were restored within the first operative week. In parallel, donor IGF1 levels decreased by 50% after living donation, and preoperative serum levels were restored after 6 months. Donors showed delayed recovery of liver function in comparison with recipients. The dynamics of IGF1 strongly correlated with routine laboratory parameters of liver function. In conclusion, recipients showed a rapid recovery of the GH/IGF1 hormonal axis and liver function after LDLT, whereas donors showed altered GH signaling and regenerative delay in the early PODs after living donation.

Intraoperative Schnellschnittuntersuchungen parapylorischer Lymphknoten bei der pyloruserhaltenden Pankreaskopfresektion: Gibt es eine klinische Relevanz?

HINTERGRUND: Die pyloruserhaltende Pankreaskopfresektion (PPPD) ist als onkologisches Standardverfahren etabliert. Lokal fortgeschrittene Tumoren können eine erweiterte Resektion erforderlich machen. Ebenso soll früheren Arbeiten zufolge bei Tumornachweis in den parapylorischen Lymphknoten (PLK) eine distale Magenresektion im Sinne einer klassischen Whipple-Operation indiziert sein. Entsprechend diesen Empfehlungen haben wir intraoperative Schnellschnittuntersuchungen der PLK in unseren Routineablauf integriert. Im Rahmen dieser Studie haben wir die klinische Relevanz dieses Vorgehens hinterfragt. METHODEN: Bei 105 onkologischen Patienten im Zeitraum von 2006-2012 bestand die Indikation zur PPPD. In allen Fällen erfolgte eine intraoperative Schnellschnittuntersuchung der PLK. Die Patienten wurden bezüglich Primärtumor, Anzahl der untersuchten Lymphknoten (LK) (gesamt und parapylorisch) sowie Auswirkungen auf das operative Konzept untersucht. Es handelt sich um eine retrospektive Studie, die auf prospektiv erhobenen Daten unserer Pankreasdatenbank basiert. ERGEBNISSE: Die Primärtumoren waren 72 Pankreaskopfkarzinome und 33 extrapankreatische Karzinome (Gallengangskarzinom, Ampullenkarzinom, Duodenalkarzinom). 73 Patienten waren nodalpositiv. Insgesamt wurden 2391 LK untersucht, von denen 325 parapylorisch lokalisiert waren. Die intraoperative Schnellschnittuntersuchung erbrachte lediglich bei 4 Patienten mit Pankreaskopfkarzinom jeweils einen positiven PLK; daraufhin erfolgte eine distale Magenresektion. In keinem der distalen Magenresektate waren Tumorresiduen nachweisbar. Lokale chirurgisch-technische Probleme im Sinne von Durchblutungsstörungen des Magens ergaben sich durch die regionale Lymphadenektomie nicht. PLK waren nur beim Pankreaskarzinom positiv. In der Subgruppe der nodalpositiven Patienten mit Pankreaskopfkarzinom hatten 8% der Patienten einen positiven PLK. SCHLUSSFOLGERUNG: Die regionale parapylorische Lymphadenektomie ist beim Pankreaskarzinom in einigen (5%) Fällen onkologisch sinnvoll. Der Nutzen einer intraoperativen Schnellschnittuntersuchung mit nachfolgender Konsequenz für eine etwaige distale Magenresektion ist anhand unserer Daten nicht belegbar.

Predicting the prognosis in acute liver failure: results from a retrospective pilot study using the LiMAx test.

BACKGROUND: Acute liver failure (ALF) is a rare but potentially life-threatening condition and liver transplantation (LTX) remains frequently the only effective therapy. Nevertheless, some patients recover without LTX but the individual indication for or against LTX remains difficult. AIM: To evaluate maximal liver function capacity (LiMAx) for predicting the prognosis of ALF. Material and methods. Clinic data of 12 patients was retrospectively analyzed to compare the different liver function test results with the patients' clinical outcome. Patients were assessed by the LiMAx test, a non-invasive breath test determining cytochrome P450 1A2 capacity using intravenous 13C-methacetin. Statistical analysis compared patients with spontaneous recovery versus non-recovery (LTX or death). RESULTS: Twelve patients (6 male, 6 female; 49 [11-72] years) with viral hepatitis (n = 2), toxic liver injury (n = 3), or cryptogenic liver failure (n = 7) were analyzed. Seven patients fully recovered from ALF and were discharged without LTX. Three patients died and two underwent LTX. The King's College Criteria (KCC) was fulfilled in only one out of five patients without recovery. The LiMAx was 19 ± 19 (16-62) for non-recovery vs. 94 ± 119 (39-378) µg/kg/h for recovery (P = 0.018). In contrast, all biochemical parameters [bilirubin (P = 0.106), creatinine (P = 0.343), AST (P = 0.53), ALT (P = 0.876) and INR (P = 0.876) were statistically indistinct. Also the Model for End-Stage Liver Disease (MELD) score did not show a difference [35 ± 4.3 (29-40) vs. 30 ± 11.5 (6-40); P = 0.27]. CONCLUSIONS: Maximal liver function capacity determined by LiMAx test is severely impaired in patients with ALF. The LiMAx test might be effective in predicting the individual prognosis and the need for LTX in ALF.

Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients.

BACKGROUND: Survivin, a member of the inhibitor of apoptosis-protein family suppresses apoptosis and regulates cell division. It is strongly overexpressed in the vast majority of cancers. We were interested if survivin detected by immunohistochemistry has prognostic relevance especially for patients of the two soft tissue sarcoma entities leiomyosarcoma and synovial sarcoma. METHODS: Tumors of leiomyosarcoma (n = 24) and synovial sarcoma patients (n = 26) were investigated for their expression of survivin by immunohistochemistry. Survivin expression was assessed in the cytoplasm and the nucleus of tumor cells using an immunoreactive scoring system (IRS). RESULTS: We detected a survivin expression (IRS > 2) in the cytoplasm of 20 leiomyosarcomas and 22 synovial sarcomas and in the nucleus of 12 leiomyosarcomas and 9 synovial sarcomas, respectively. There was no significant difference between leiomyosarcoma and synovial sarcoma samples in their cytoplasmic or nuclear expression of survivin. Next, all sarcoma patients were separated in four groups according to their survivin expression in the cytoplasm and in the nucleus: group 1: negative (IRS 0 to 2); group 2: weak (IRS 3 to 4); group 3: moderate (IRS 6 to 8); group 4: strong (IRS 9 to 12). In a multivariate Cox's regression hazard analysis survivin expression detected in the cytoplasm or in the nucleus was significantly associated with overall survival of patients in group 3 (RR = 5.7; P = 0.004 and RR = 5.7; P = 0.022, respectively) compared to group 2 (reference). Patients whose tumors showed both a moderate/strong expression of survivin in the cytoplasm and a moderate expression of survivin in the nucleus (in both compartments IRS > or = 6) possessed a 24.8-fold increased risk of tumor-related death (P = 0.003) compared to patients with a weak expression of survivin both in the cytoplasm and in the nucleus. CONCLUSION: Survivin protein expression in the cytoplasma and in the nucleus detected by immunohistochemistry is significantly associated with prognosis of leiomyosarcoma and synovial sarcoma patients.