Porcine model characterizing various parameters assessing the outcome after acetaminophen intoxication induced acute liver failure

AIM To investigate the changes of hemodynamic and laboratory parameters during the course of acute liver failure following acetaminophen overdose.METHODS Eight pigs underwent a midline laparotomy following jejunal catheter placement for further acetaminophen intoxication and positioning of a portal vein Doppler flow-probe. Acute liver failure was realized by intrajejunal acetaminophen administration in six animals, two animals were sham operated. All animals were invasively monitored and received standardized intensive care support throughout the study. Portal blood flow, hemodynamic and ventilation parameters were continuously recorded. Laboratory parameters were analysed every eight hours. Liver biopsies were sampled every 24 h following intoxication and upon autopsy.RESULTS Acute liver failure (ALF) occurred after 28 ± 5 h resulted in multiple organ failure and death despite maximal support after further 21 ± 1 h (study end). Portal blood flow (baseline 1100 ± 156 m L/min) increased to a maximum flow of 1873 ± 175 m L/min at manifestation of ALF, which was significantly elevated(P < 0.01). Immediately after peaking, portal flow declined rapidly to 283 ± 135 m L/min at study end. Thrombocyte values (baseline 307 × 103/μL± 34 × 103/μL) of intoxicated animals declined slowly to values of 145 × 103/μL± 46 × 103/μL when liver failure occurred. Subsequent appearance of severe thrombocytopenia in liver failure resulted in values of 11 × 103/μL± 3 × 103/μL preceding fatality within few hours which was significant(P > 0.01).CONCLUSION Declining portal blood flow and subsequent severe thrombocytopenia after acetaminophen intoxication precede fatality in a porcine acute liver failure model.

Incidence of leukopenia after intraperitoneal vs combined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.METHODS: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort(n = 32) received Mitomycin C(MMC)-based HIPEC intraperitoneally(35 mg/m2 for 90 min) and the second cohort(n = 10) received a bidirectional therapy consisting of oxaliplatin(OX)(300 mg/m2 for 30 min) intraperitoneally and 5-fluorouracil(5-FU) 400 mg/m2 plus folinic acid 20 mg/m2 intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC(completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery(CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as < 4000 cells/m3. RESULTS: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group(10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients(33%) required medical treatment. Patients affected by leukopenia were predominantly female(7/10 patients) and older than 50 years(8/10 patients). Thelength of hospital stay tended to be higher in the MMCgroup without reaching statistical significance(22.5± 11 vs 16.5 ± 3.5 d). Length of operation(08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger postHIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC protocols primarily affecting females and older patients.

Growth hormone abolishes the negative effects of everolimus on intestinal wound healing

AIM: To investigate whether the simultaneous treatment with human growth hormone(h GH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each(Ⅰ: vehicle; Ⅱ: everolimus 3 mg/kg po; Ⅲ: everolimus 3 mg/kg po + h GH 2.5 mg/kg sc). Animals were pretreated with h GH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical(Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological(cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with h GH resulted in considerably higher values(Ⅰ: 134 ± 19 mm Hg, Ⅱ: 85 ± 25 mm Hg, Ⅲ: 114 ± 25 mm Hg; P < 0.05,Ⅰvs Ⅱ; P = 0.09,Ⅰvs Ⅲ and Ⅱ vs Ⅲ) Hydroxyproline concentration was significantly increased by h GH compared to everolimus alone(Ⅰ: 14.9 ± 2.5 μg/mg, Ⅱ: 8.9 ± 3.6 μg/mg, Ⅲ: 11.9 ± 2.8 μg/mg; P < 0.05,?Ⅰvs Ⅱ/Ⅲ and Ⅱ vs Ⅲ). The number of MPO-positive cells was reduced significantly by h GHcompared to everolimus alone(Ⅰ: 10 ± 1 n/mm^2, Ⅱ: 15 ± 3 n/mm^2, Ⅲ: 9 ± 2 n/mm^2; P < 0.05,Ⅰvs Ⅱ and Ⅱ vs Ⅲ), while the number of PCNA-positive cells were increased by h GH(Ⅰ: 28 ± 3 /mm^2, Ⅱ: 12 ± 3 /mm^2, Ⅲ: 26 ± 12 /mm^2; P < 0.05,?Ⅰ?vs Ⅱ and Ⅱ vs Ⅲ). Corresponding to these biochemical findings, HEhistology revealed significantly increased amount of granulation tissue in h GH-treated animals.CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with h GH. Both inflammation as well as collagen deposition is influenced by h GH.

Significance of multivisceral resections in oncologic surgery: A systematic review of the literature

BACKGROUND Multivisceral resections (MVR) are often necessary to reach clear resections margins but are associated with relevant morbidity and mortality. Factors associated with favorable oncologic outcomes and elevated morbidity rates are not clearly defined. AIM To systematically review the literature on oncologic long-term outcomes and morbidity and mortality in cancer surgery a systematic review of the literature was performed. METHODS PubMed was searched for relevant articles (published from 2000 to 2018). Retrieved abstracts were independently screened for relevance and data were extracted from selected studies by two researchers. RESULTS Included were 37 studies with 3112 patients receiving MVR for colorectal cancer (1095 for colon cancer, 1357 for rectal cancer, and in 660 patients origin was not specified). The most common resected organs were the small intestine, bladder and reproductive organs. Median postoperative morbidity rate was 37.9%(range: 7% to 76.6%) and median postoperative mortality rate was 1.3%(range: 0% to 10%). The median conversion rate for laparoscopic MVR was 7.9%(range: 4.5% to 33%). The median blood loss was lower after laparoscopic MVR compared to the open approach (60 mL vs 638 mL). Lymph-node harvest after laparoscopic MVR was comparable. Report on survival rates was heterogeneous, but the 5-year overall-survival rate ranged from 36.7% to 90%, being worst in recurrent rectalcancer patients with a median 5-year overall survival of 23%. R0 -resection, primary disease setting and no lymph-node or lymphovascular involvement were the strongest predictors for long-term survival. The presence of true malignant adhesions was not exclusively associated with poorer prognosis. Included were 16 studies with 1.600 patients receiving MVR for gastric cancer. The rate of morbidity ranged from 11.8% to 59.8%, and the main postoperative complications were pancreatic fistulas and pancreatitis, anastomotic leakage, cardiopulmonary events and post-operative bleedings. Total mortality was between 0% and 13.6% with an R0 -resection achieved in 38.4% to 100% of patients. Patients after R0 resection had 5-year overall survival rates of 24.1% to 37.8%. CONCLUSION MVR provides, in a selected subset of patients, the possibility for good long-term results with acceptable morbidity rates. Unlikelihood of achieving R0 -status, lymphovascular- and lymph -node involvement, recurrent disease setting and the presence of metastatic disease should be regarded as relative contraindications for MVR.

Algorithm-based arterial blood sampling recognition increasing safety in point-of-care diagnostics

AIM To detect blood withdrawal for patients with arterial blood pressure monitoring to increase patient safety and provide better sample dating.METHODS Blood pressure information obtained from a patient monitor was fed as a real-time data stream to an experimental medical framework. This framework was connected to an analytical application which observes changes in systolic, diastolic and mean pressure to determine anomalies in the continuous data stream. Detection was based on an increased mean blood pressure caused by the closing of the withdrawal three-way tap and an absence of systolic and diastolic measurements during this manipulation. For evaluation of the proposed algorithm, measured data from animal studies in healthy pigs were used.RESULTS Using this novel approach for processing real-time measurement data of arterial pressure monitoring, the exact time of blood withdrawal could be successfully detected retrospectively and in real-time. The algorithm was able to detect 422 of 434(97%) blood withdrawals for blood gas analysis in the retrospective analysis of 7 study trials. Additionally, 64 sampling events for other procedures like laboratory and activated clotting time analyses were detected. The proposed algorithm achieved a sensitivity of 0.97, a precision of 0.96 and an F1 score of 0.97.CONCLUSION Arterial blood pressure monitoring data can be used toperform an accurate identification of individual blood samplings in order to reduce sample mix-ups and thereby increase patient safety.