Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Laparoscopic repeat liver resection for hepatocellular carcinoma: a multicentre propensity score-based study.

BACKGROUND: In the absence of randomized controlled data and even propensity-matched data, indications for, and outcomes of, laparoscopic repeat liver resection for hepatocellular carcinoma (HCC) remain uncertain. This study aimed to clarify the current indications for laparoscopic repeat liver resection for HCC, and to evaluate outcomes. METHODS: Forty-two liver surgery centres around the world registered patients who underwent repeat liver resection for HCC. Patient characteristics, preoperative liver function, tumour characteristics, surgical method, and short- and long-term outcomes were recorded. RESULTS: Analyses showed that the laparoscopic procedure was generally used in patients with relatively poor performance status and liver function, but favourable tumour characteristics. Intraoperative blood loss (mean(s.d.) 254(551) versus 748(1128) ml; P < 0·001), duration of operation (248(156) versus 285(167) min; P < 0·001), morbidity (12·7 versus 18·1 per cent; P = 0·006) and duration of postoperative hospital stay (10·1(14·3) versus 11·8(11·8) days; P = 0·013) were significantly reduced for laparoscopic compared with open procedures, whereas survival time was comparable (median 10·04 versus 8·94 years; P = 0·297). Propensity score matching showed that laparoscopic repeat liver resection for HCC resulted in less intraoperative blood loss (268(730) versus 497(784) ml; P = 0·001) and a longer operation time (272(187) versus 232(129); P = 0·007) than the open approach, and similar survival time (12·55 versus 8·94 years; P = 0·086). CONCLUSION: Laparoscopic repeat liver resection is feasible in selected patients with recurrent HCC.

ANTECEDENTES: Dado que no existen ensayos clínicos controlados ni estudios de datos emparejados por puntaje de propensión, todavía hay dudas sobre las indicaciones y los resultados de la resección iterativa laparocópica de un carcinoma hepatocelular (hepatocellular carcinoma, HCC). Este estudio tuvo como objetivo esclarecer las indicaciones actuales y los resultados de la resección hepática laparoscópica iterativa del HCC. MÉTODOS: Se incluyeron los pacientes de 42 centros de cirugía hepática a nivel mundial en los que se había realizado una resección hepática iterativa por HCC. Se analizaron las características del paciente, la función hepática preoperatoria, las características del tumor, el abordaje quirúrgico y los resultados a corto y largo plazo. RESULTADOS: El análisis demostró que la vía laparoscópica generalmente se utilizaba en pacientes con carácteristicas tumorales favorables, pero con estado funcional y función hepatica relativamente peores. La pérdida de sangre intraoperatoria (254,3 ± 551,2 versus 748,0 ± 1127,7 mL, P < 0,001), la duración de la intervención (247,6 ± 155,8 versus 285,1 ± 167,0 minutos, P < 0,001), la morbilidad (12,7 versus 18,1%, P = 0,005) y la estancia hospitalaria postoperatoria (10,07 ± 14,29 versus 11,80 ± 11,79 días, P = 0,010) fueron significativamente menores para los pacientes tratados por via laparoscópica en comparacion con la vía abierta, mientra que el tiempo de supervivencia fue comparable (mediana 10,04 versus 8,94 años, P = 0,297). El estudio de emparejamiento por puntaje de propensión mostró que la resección hepática iterativa por vía laparoscópica de un HCC (frente a la vía abierta) conllevaba una menor pérdida sanguínea intraoperatoria (268,0 ± 730,2 versus 496,5 ± 784,2 mL, P = 0,01), una mayor duración de la intervención (272,1 ± 187,2 versus 231,8 ± 129,1 minutos , P = 0,07) y un tiempo de supervivencia similar (mediana 12,55 versus 8,94 años, P = 0,0855). CONCLUSIÓN: La resección hepática iterativa por vía laparoscópica es factible en pacientes seleccionados con HCC recidivado.

Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer.

BACKGROUND: This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day(-1) based on body surface area (BSA), orally, days 1-28, every 6 weeks) or SOX (S-1 80/100/120 mg day(-1) based on BSA, orally, days 1-14, plus oxaliplatin 100 mg m(-2), intravenously, day 1, every 3 weeks). The primary end point was PFS. RESULTS: Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65-1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79-1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%). CONCLUSIONS: Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.

Comparison of short-term outcomes of robotic and laparoscopic transabdominal peritoneal repair for unilateral inguinal hernia: a propensity-score matched analysis.

PURPOSE: This study aimed to compare perioperative outcomes of robotic and laparoscopic transabdominal peritoneal repair (TAPP) for unilateral inguinal hernia. METHODS: This single institutional retrospective cohort study used de-identified data of patients who underwent robotic TAPP (R-TAPP) or laparoscopic TAPP (L-TAPP) for unilateral inguinal hernia between January 1, 2016 and October 31, 2021. Two cohorts were propensity matched, and data were analyzed. The learning curve was evaluated in the R-TAPP group. RESULTS: Among 938 patients analyzed, 704 were included. After propensity-score matching, 80 patients were included in each group. The difference in operative time between R-TAPP and L-TAPP groups was 10 min (99.5 and 89.5 min, p = 0.087); however, console/laparoscopic time was similar (67 and 66 min, p = 0.71). The dissection time for medial-type hernia in the R-TAPP group was marginally shorter than that in the L-TAPP group (17 and 27 min, p = 0.056); however, there was no difference for lateral-type hernia (38.5 and 40 min p = 0.37). Perioperative variables, including estimated blood loss, postoperative hospital stay, and postoperative pain, had no significant difference, and chronic pain, which needed medication or intervention, was not observed in each group. The number of cases needed to achieve plateau performance was 7-10 in the R-TAPP group. CONCLUSION: This study suggests that R-TAPP was safely introduced, and its perioperative outcomes were not inferior to those of L-TAPP. A shorter dissection time for medial-type hernia might be due to the robot's advantages, and a fast-learning curve could help with the early standardization of the procedure.

Utility of Robot-assisted Laparoscopic Transabdominal Preperitoneal Repair of Inguinal Hernia Following Robot-assisted Laparoscopic Radical Prostatectomy.

BACKGROUND: To evaluate the utility of robot-assisted laparoscopic transabdominal preperitoneal repair (R-TAPP) of postprostatectomy inguinal hernia (PIH) in patients who underwent robot-assisted laparoscopic radical prostatectomy (RALP). PATIENTS AND METHODS: This was a prospective, single-centre retrospective cohort study. R-TAPP was conducted in 74 consecutive patients from September 2016 to March 2020. With the exception of women and patients who underwent previous abdominal surgery, 70 patients were classified into two groups based on the absence or presence of PIH. Their data were retrospectively compared to those who had not undergone RALP. RESULTS: The median operative time for the PIH group was longer compared to the non-PIH group. However, postoperative complications, including seroma formation, haematoma and surgical site infections, were not significantly different between the groups. The estimated blood loss was small, and hospitalisation duration was 1 day in all cases. Moreover, there were no hernia recurrences within the 90-day follow-up period in either group. CONCLUSION: R-TAPP is a feasible and safe approach for inguinal hernia repair, even in patients who undergo RALP for prostate cancer.

Changes in serum S100A12 and sRAGE associated with improvement of the PaO(2)/FiO(2) ratio following PMX-DHP therapy for postoperative septic shock.

BACKGROUND: Endotoxin (Et) adsorption therapy with a column of polymyxin B-immobilized fibers (PMX) is effective in improving the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (PaO(2)/FiO(2) ratio) and increasing mean arterial blood pressure (MAP) in sepsis. S100A12 and soluble receptor for advanced glycation end product (sRAGE) are useful as early markers of acute lung injury. PURPOSE: To investigate the effect of improving the PaO(2)/FiO(2) ratio by PMX-direct hemoperfusion (PMX-DHP) on production of S100A12 and sRAGE. SUBJECTS AND METHODS: Sepsis patients after surgery for perforation of the lower gastrointestinal tract were adopted as the subjects. We retrospectively reviewed the cases of 20 patients on mechanical ventilation and continuous administration of norepinephrine. We recorded PaO(2)/FiO(2) ratio, MAP, and norepinephrine doses. S100A12, sRAGE, and Et levels were measured before and after PMX-DHP. RESULTS: The PaO(2)/FiO(2) ratio and MAP improved significantly after PMX-DHP (p < 0.05). S100A12 and Et decreased significantly after PMX-DHP (p < 0.05). No differences were observed in sRAGE. CONCLUSION: S100A12 is useful as a marker that reflected improvement in the PaO(2)/FiO(2) ratio after PMX-DHP. We consider PMX-DHP to be useful as adjunctive therapy for sepsis that reduces the Et and corrects the pathology in the early stage.

Preliminary study on glucose control with an artificial pancreas in postoperative sepsis patients.

BACKGROUND: Glucose control is essential to avoid hypoglycemia in postoperative patients. AIM: To conduct a preliminary examination to evaluate the feasibility of the use of an artificial pancreas for glucose control as well as the accuracy of assessment by the artificial pancreas of the insulin dose required. SUBJECTS AND METHODS: Glucose control using an artificial pancreas was undertaken in 8 postoperative sepsis patients. The blood glucose level was set at 80-150 mg/dl. Blood glucose levels over time, insulin dose requirements, and occurrence of hypoglycemia (≤40 mg/dl) were recorded for each patient. The patients were divided into 2 groups based on the total insulin dose they received over the 7 days (HG, n = 4: consisting of patients who required a higher insulin dose; LG, n = 4: patients who required a lower insulin dose). The data of the 2 groups were analyzed retrospectively. RESULTS: The blood glucose level before glucose control was 203.3 ± 9.9 mg/dl and could be controlled in all patients to within the target range. No hypoglycemia events were recorded for any of the patients. The insulin dose in the HG and LG groups was 21,824.8 ± 6,030.4 and 6,254.5 ± 3,402.3 mU/kg (p < 0.05). CONCLUSIONS: Accurate glucose control could be achieved with the artificial pancreas.

Safety and feasibility of laparoscopic surgery for elderly rectal cancer patients in Japan: a nationwide study.

BACKGROUND: This study aimed to analyse the perioperative results from a national dataset of rectal cancer resections in elderly patients. METHODS: The clinical records of patients undergoing rectal cancer surgery between 2012 and 2014 were retrieved from the Japanese National Clinical Database and analysed retrospectively. Patients were categorized according to age and those 80 years or older were defined as elderly. Subgroups were also defined according to the surgical approach (laparoscopy versus open surgery). The short-term outcomes, including mortality, anastomotic leak, surgical site infections and medical complications were compared between subgroups. RESULTS: Of 56 175 patients undergoing rectal cancer surgery, some 6717 patients were elderly and laparoscopy was performed in 46.8 per cent of the sample. When comparing laparoscopy and open surgery in elderly patients, the operative mortality rate (1.5 versus 2.8 per cent; P < 0.001), the incidence of anastomotic leakage (5.2 versus 6.5 per cent; P = 0.026), surgical site infections (6.0 versus 8.0 per cent; P = 0.001), pneumonia (1.4 versus 2.5 per cent; P = 0.001), renal failure (0.7 versus 1.3 per cent; P = 0.016) and cardiac events (0.3 versus 0.8 per cent; P = 0.008) were lower for laparoscopy than for open surgery. The overall complication rate in elderly patients (19.5 per cent) was comparable to that in the younger group (P = 0.07). However, incidence of systemic complications was significantly higher in elderly than in younger patients (all P < 0.001). CONCLUSION: Laparoscopy was safe and feasible in elderly patients compared with open surgery. However, the rates of systemic complications were significantly higher than in younger patients.

Minimally invasive surgical enucleation for esophageal leiomyoma: report of seven cases.

Benign esophageal tumor is a rare entity, with leiomyoma being the most common lesion. We present our experience with enucleation of esophageal leiomyomas using a minimally invasive approach. Between March 1998 and June 2008, seven patients with esophageal leiomyoma underwent right thoracosopic enucleation (n=4) or laparoscopic transhiatal enucleation (n=3). A Dor (n=2) or Toupet fundoplication (n=1) were added for laparoscopic procedure. The mean tumor size was 3.9 cm (range, 1.5-5.5 cm). Tumor locations were upper (n=2), middle (n=1), and lower (n=4) thirds of the esophagus. No major morbidities including postoperative leakage or mortalities occurred. At a mean follow-up period of 60.1 months (range, 14-260 months), no evidence of recurrences were observed. Thoracoscopic and laparoscopic transhiatal enucleation for esophageal leiomyomas is a safe and feasible procedure. The optimal approaches should be tailored based on the location and size of the tumor.

Laparoscopic Heller myotomy with Dor fundoplication for achalasia: long-term outcomes and effect on chest pain.

The aim of the present study was to evaluate the long-term outcomes of laparoscopic Heller myotomy with Dor fundoplication (LHD) and its effect on chest pain. Between June 1995 and August 2009, a total of 35 patients with achalasia underwent an LHD. The symptom scores were calculated by combining the frequency and the severity. Pre- and postoperative evaluations included symptom score, radiology, manometry, and 24-hour pH manometry. Median total symptom score was significantly lower than the preoperative score (19 vs 4, P < 0.001) at a median follow-up of 94 months. Among the 35 patients, 18 (51%) had chest pain. The frequency of chest pain was similar for the pre- and postoperative scores, but the severity tended to be less. Median esophageal diameter (5.4 cm vs 3.5 cm, P < 0.001) and lower esophageal sphincter pressure (41 mmHg vs 8.9 mmHg, P < 0.001) were significantly reduced after surgery. Median age, duration of symptoms, esophageal diameter, and lower esophageal sphincter pressure were similar between patients with and without chest pain prior to surgery. No significant differences were observed between the two groups in terms of amplitude, duration, and frequency of contractions from the findings of postoperative 24-hour esophageal manometry. Chest pain resolved in three patients (17%) and improved in seven patients (39%) after surgery. LHD can durably relieve achalasic symptoms of both dysphagia and regurgitation, and it can be considered the surgical procedure of choice. However, achalasic chest pain does not always seem to be related with patient characteristics and manometric findings.

Ten-year experience of totally laparoscopic liver resection in a single institution.

BACKGROUND: Recent developments in liver surgery include the introduction of laparoscopic liver resection. The aim of the present study was to review a single institution's 10-year experience of totally laparoscopic liver resection (TLLR). METHODS: Between May 1997 and April 2008, 82 patients underwent TLLR for hepatocellular carcinoma (HCC) (37 patients), liver metastases (39) and benign liver lesions (six). Operations included 69 laparoscopic wedge resections, 11 laparoscopic left lateral sectionectomies and two thoracoscopic wedge resections. Nine patients underwent simultaneous laparoscopic resection of colorectal primary cancer and synchronous liver metastases. RESULTS: Median operating time was 177 (range 70-430) min and blood loss 64 (range 1-917) ml. Median tumour size and surgical margin were 25 (range 15-85) and 6 (range 0-40) mm respectively. One procedure was converted to a laparoscopically assisted hepatectomy. Three patients developed complications. Median postoperative stay was 9 (range 3-37) days. The overall 5-year survival rate after surgery for HCC and colorectal metastases was 53 and 64 per cent respectively. CONCLUSION: TLLR can be performed safely for a variety of primary and secondary liver tumours, and seems to offer at least short-term benefits in selected patients.

Correlation of motility and neuronal integrity with a focus on the grade of intestinal allograft rejection.

Intestinal graft motility after small bowel transplantation (SBT) is poorly characterized. The aim of this study was to compare motor patterns with myenteric neuronal cell population as a parameter of graft viability at various degrees of acute cellular rejection (ACR). Three grades of ACR were achieved in orthotopic allografts. Syngeneic transplants and allografts with immunosuppression served as controls. Motor activities were recorded using strain gauge force transducers and analyzed visually. Quantifications of myenteric neurons in whole mounts of intestinal grafts were used to evaluate neuronal population. A typical migrating motor complex (MMC) was found in syngeneic and allogenic transplants with immunosuppression. A high prevalence of discrete clustered contractions (DCC) and nonpropagating contractions (NPC) without MMC was seen in moderately and severely rejected allografts. Neuronal cell loss in the allografts, which could be one of the causes of motor dysfunction, was noted in moderate rejection (19.3%) and progressed until severe rejection (60.1%). Monitoring motility patterns in SBT could be an effective tool for assessing intestinal rejection. Allograft dysmotility, such as absence of MMC and high prevalence of DCC or NPC, could be useful markers of progression of acute rejection and help guide treatment decisions.

Functioning adrenocortical oncocytoma: the first documented case producing interleukin-6 and review of the literature.

Adrenocortical oncocytoma is an extremely rare and predominantly non-functioning tumor. We herein report the first case of an adrenocortical oncocytoma that produces interleukin (IL)-6. A 38-yr-old woman was referred for treatment of a 4-cm adrenal mass. Laboratory test results showed elevated inflammatory parameters. Intriguingly, IL-6 serum level was also high at 30 pg/ml (normal 0-4 pg/ml). The patient underwent laparoscopic right adrenalectomy. Microscopic examination showed that the tumor was an adrenocortical oncocytoma with a unique peripheral lymphoid cuff with germinal centers. Electron microscopy demonstrated that the cytoplasm of the neoplastic cells was packed with numerous abnormal mitochondria. Three observations lead us to consider that this tumor was the primary source of serum IL-6. First, the IL-6 level in blood collected from the right adrenal vein was highest (527 pg/ml) among intra-operative blood samples. Second, neoplastic cells stained positively for IL-6. Third, the serum IL-6 returned to normal levels immediately after surgery.

Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli.

Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism.

Impact of Portal Hemodynamic Changes in Partial Liver Grafts on Short-Term Graft Regeneration in Living Donor Liver Transplantation.

BACKGROUND: Regeneration of partial liver grafts is critical for successful living donor liver transplantation (LDLT), especially in adult recipients. The purpose of this study was to investigate the intraoperative hemodynamic changes in partial liver grafts and characterize their potential impact on post-transplant liver regeneration in LDLT. METHODS: We examined the portal venous flow (PVF) and hepatic arterial flow (HAF) to partial liver grafts by means of ultrasonic transit time flowmeter of donors immediately before graft retrieval and of the corresponding recipients after vascular reconstruction in 48 LDLT cases. We evaluated post-transplant liver regeneration according to the changes in graft liver volume between the time of transplantation and the 7th post-transplant day. RESULTS: There was a significant increase in PVF to the partial liver grafts in recipients (rPVF) compared with that in donors. In contrast, graft HAF in recipients significantly decreased compared with that in donors. The rPVF inversely correlated with graft weight (GW)-recipient body weight ratio (GRWR), whereas HAF volume showed no significant correlation. The rPVF/GW positively correlated with the rate of liver regeneration (GRR), which inversely correlated with GRWR. The rPVF/GW was significantly higher, and GRR tended to be larger in the small graft group than in the non-small graft group. CONCLUSIONS: Intraoperative portal hemodynamic changes in partial liver grafts strongly affect their post-transplant regeneration. In particular, in small liver grafts, an immediate and remarkable increase in graft PVF may contribute to rapid liver regeneration after LDLT if the increased PVF remains within a safe range.

Chemotherapy-induced Nausea and Vomiting in Patients with Hepatobiliary and Pancreatic Cancer Treated with Chemotherapy: A Prospective Observational Study by the CINV Study Group of Japan.

BACKGROUND: This study investigated the prevalence of chemotherapy-induced nausea and vomiting (CINV) in patients with hepatobiliary-pancreatic (HBP) cancer in a prospective nationwide survey. PATIENTS AND METHODS: One hundred patients with HBP cancer (biliary tract cancer; n=70, hepatocellular carcinoma; n=20, and pancreatic cancer; n=10) who received chemotherapy for the first time were analyzed. Medical personnel were surveyed to examine the accuracy of their predicted frequency of CINV. RESULTS: The compliance rate with the Japanese guideline with highly emetogenic chemotherapy was 36/89 (40%). Although the prevalence of CINV in patients with HBP cancer was significantly lower than that of the total 1,910 patients with cancer, the prevalence of delayed CINV in patients with HBP cancer was as high as 28%. The survey results suggested that the medical staff tended to overestimate the incidence of CINV. CONCLUSION: CINV appears to be controlled under management according to the guidelines, but delayed nausea remains prevalent and requires further investigation.

Overexpression of truncated IkappaBalpha induces TNF-alpha-dependent apoptosis in human vascular smooth muscle cells.

Dysregulation of apoptosis is one of the likely underlying mechanisms of neointimal thickening, a disorder in which proinflammatory cytokines may influence the function of vascular smooth muscle cells (VSMCs) and contribute to atherogenesis. One of these cytokines, tumor necrosis factor-alpha (TNF-alpha), induces 2 possibly conflicting pathways, 1 leading to the activation of nuclear factor-kappaB (NF-kappaB) and the other leading to caspase-mediated apoptosis. We investigated whether specific inhibition of NF-kappaB affects TNF-alpha-dependent apoptosis in human VSMCs. To inhibit NF-kappaB activation specifically, we constructed a recombinant adenovirus vector expressing a truncated form of the inhibitor protein IkappaBalpha (AdexIkappaBDeltaN) that lacks the phosphorylation sites essential for activation of NF-kappaB. The IkappaBDeltaN was overexpressed by adenoviral infection and was resistant to stimulus-dependent degradation. Electromobility gel shift and luciferase assays demonstrated that overexpression of IkappaBDeltaN inhibited NF-kappaB activation induced by TNF-alpha or interleukin-1beta (IL-1beta). In cells overexpressing IkappaBDeltaN, TNF-alpha dramatically induced apoptosis, whereas IL-1beta had no effect. The induction was suppressed by treatment with a selective inhibitor of the caspase-3 family, Z-DEVD-fmk, and the overexpression of IkappaBDeltaN induced TNF-alpha-mediated caspase-3 and caspase-2 activity. These results indicate that overexpression of IkappaBDeltaN induces TNF-alpha-dependent apoptosis by efficient and specific suppression of NF-kappaB and upregulation of caspase-3 and caspase-2 activity in human VSMCs. Our findings suggest that adenovirus-mediated IkappaBDeltaN gene transfer may be useful in the treatment of disorders associated with inflammatory conditions, such as the response to vascular injury and atherosclerosis.

Interleukin 1 receptor blockade reduces tumor necrosis factor production, tissue injury, and mortality after hepatic ischemia-reperfusion in the rat.

The inflammatory cytokines interleukin (IL) 1 and tumor necrosis factor (TNF) may play an important role in hepatic ischemia-reperfusion (I/R) injury. To study the role of IL-1 in hepatic I-R injury, we investigated the effect of pretreatment with IL-1 receptor antagonist (IL-1ra) on the production of IL-1, TNF, histological findings in the liver, and the survival rate for 7 days. Rats were subjected to 90 min of partial liver warm ischemia by clamping the vessels of the left and middle lobes. In the IL-1ra-treated group, IL-1ra was given 5 min before liver ischemia was induced. IL-1alpha and TNF levels were determined in blood and liver at 0, 30, 90, and 180 min after reperfusion. In a second experiment to determine the effect of IL-1ra pretreatment on survival rate, after 90 min of partial liver ischemia, the right lateral and caudate lobes were excised, leaving only the ischemic lobes. In both groups, IL-1alpha was undetectable in blood, but increased in liver tissue. TNF increased in both blood and liver tissue as reperfusion time increased. Histological evidence of tissue injury was minimal in the IL-1ra-treated group. Furthermore, in the IL-1ra-treated group, the production of TNF decreased in both blood and liver tissue compared with the nontreated group. Survival rates in the IL-1ra-treated and nontreated group were 80% and 30%, respectively. The data demonstrated that the production of IL-1 and TNF increases in hepatic I-R injury and that pretreatment with IL-1ra protects the liver from ischemic insult, indicating an important role for IL-1 in I-R injury.

Up-regulation of oxygen-derived free radicals by interleukin-1 in hepatic ischemia/reperfusion injury.

BACKGROUND: Oxygen-derived free radicals (FRs) are critical mediators of ischemia/reperfusion injury. Inflammatory cytokines have been shown to play important roles in tissue injury. To examine the relationship between FRs and interleukin-1 (IL-1) in hepatic ischemia/reperfusion injury, we used interleukin-1 receptor antagonist (IL-1ra) to block endogenous IL-1 production in a rat model of hepatic ischemia/reperfusion. METHODS: Female SD rats were subjected to 30 min of hepatic ischemia followed by reperfusion. The animals were divided into two groups, control group and IL-1ra-treated group, according to the rinse solution. In both groups, FR production, histological changes, and interactions between leukocytes and endothelial cells were analyzed in the course of reperfusion. RESULTS: In the control group, production of FRs increased significantly after 60 min of reperfusion. After 60 and 180 min of reperfusion, histological examination showed atrophy and degeneration of hepatocytes. Hepatic microcirculation demonstrated a marked increase in the number of leukocytes adherent to endothelial cells and of injured cells after reperfusion. In the IL-1ra-treated group, IL-1ra pretreatment markedly reduced FR production after 60 min of reperfusion, the number of leukocytes adherent to endothelial cells, and tissue injury. CONCLUSION: These data clearly show an important role for IL-1 in the induction of FR production, leukocyte adhesion, and tissue injury after hepatic ischemia/reperfusion injury.

Efficacy of intraportal infusion of prostaglandin E1 to improve the hepatic blood flow and graft viability in porcine liver transplantation.

BACKGROUND: Prostaglandin E1 (PGE1) has been reported to have a protective effect in experimental and clinical models of liver damage. The aim of this study was to elucidate the effects of the intraportal infusion of PGE1 on hepatic blood flow and graft viability after orthotopic liver transplantation in pigs. METHODS: First, the hepatic arterial flow (HAF), portal venous flow (PVF), and liver tissue blood flow (LTBF) were measured during the continuous intravenous or intraportal infusion of PGE1. Second, two groups of pigs underwent orthotopic liver transplantation: group A, untreated controls; and group B, animals that received intraportal PGE1 for 2 hr after vascular reconstruction of the allograft. Changes in HAF, PVF, LTBF, and hepatic function were measured. RESULTS: The intraportal infusion of PGE1 significantly increased HAF and had no effect on blood pressure, PVF, or LTBF. In group B, HAF and LTBF increased significantly with time. In group A, HAF remained unchanged and a decrease in LTBF was observed. Group B exhibited a higher arterial ketone body ratio and a greater bile flow compared with group A. A significant elevation in serum glutamic oxaloacetic transaminase concentration was observed in group A, but not in group B. CONCLUSIONS: This study demonstrates that the intraportal infusion of PGE1 improves hepatic allograft blood flow, predominantly through an effect on HAF, and may improve graft viability after orthotopic liver transplantation.