Giant hemorrhagic pancreatic pseudocyst with suspected cystic pancreatic tumor: a case report.

Pancreatic pseudocysts are surrounded by a non-epithelialized wall confined to the pancreas and localized to the pancreatic tissue or adjacent pancreatic cavity. In contrast, pancreatic cystic tumors occur less frequently than solid lesions and are often detected incidentally on imaging. Regarding the qualitative diagnosis of pancreatic pseudocysts, it is important to differentiate them from neoplastic cysts. We report the case of a 74-year-old woman with a giant hemorrhagic pancreatic pseudocyst and a suspected cystic pancreatic tumor, wherein distal pancreatectomy and splenectomy with lymph node dissection were performed. The patient was discharged 11 days postsurgery, with a good postoperative course. There are no reports of giant pancreatic pseudocysts larger than 10 cm with hematoma contents. The presumptive diagnosis of pseudocysts based on imaging alone may be difficult. Surgical resection is considered when it is difficult to distinguish a giant pancreatic pseudocyst from a cystic neoplasm.

Hepatoprotective effects of baicalein against liver ischemia-reperfusion injury and partial hepatectomy in a rat model.

BACKGROUND: Baicalein is the main active flavonoid in Scutellariae Radix and is included in shosaikoto, a Kampo formula used for treating hepatitis and jaundice. However, little is known about its hepatoprotective effects against hepatic ischemia-reperfusion injury (HIRI), a severe clinical condition directly caused by interventional procedures. We aimed to investigate the hepatoprotective effects of baicalein against HIRI and partial hepatectomy (HIRI + PH) and its potential underlying mechanisms. METHODS AND RESULTS: Male Sprague-Dawley rats received either baicalein (5 mg/kg) or saline intraperitoneally and underwent a 70% hepatectomy 15 min after hepatic ischemia. After reperfusion, liver and blood samples were collected. Survival was monitored 30 min after hepatic ischemia and hepatectomy. In interleukin 1ß (IL-1ß)-treated primary cultured rat hepatocytes, the influence of baicalein on inflammatory mediator production and the associated signaling pathway was analyzed. Baicalein suppressed apoptosis and neutrophil infiltration, which are the features of HIRI + PH treatment-induced histological injury. Baicalein also reduced the mRNA expression of the proinflammatory cytokine tumor necrosis factor-α (TNF-α). In addition, HIRI + PH treatment induced liver enzyme deviations in the serum and hypertrophy of the remnant liver, which were suppressed by baicalein. In the lethal HIRI + PH treatment group, baicalein significantly reduced mortality. In IL-1ß-treated rat hepatocytes, baicalein suppressed TNF-α and chemokine mRNA expression as well as the activation of nuclear factor-kappa B (NF-κB) and Akt. CONCLUSIONS: Baicalein treatment attenuates HIRI + PH-induced liver injury and may promote survival. This potential hepatoprotection may be partly related to suppressing inflammatory gene induction through the inhibition of NF-κB activity and Akt signaling in hepatocytes.

Sulforaphane Is Protective against Warm Ischemia/Reperfusion Injury and Partial Hepatectomy in Rats.

Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion injury (HIRI) is unclear. To investigate the hepatoprotective effects of SFN using an in vivo model of HIRI and partial hepatectomy (HIRI + PH), rats were subjected to 15 min of hepatic ischemia with blood inflow occlusion, followed by 70% hepatectomy and release of the inflow occlusion. SFN (5 mg/kg) or saline was randomly injected intraperitoneally 1 and 24 h before ischemia. Alternatively, ischemia was prolonged for 30 min to evaluate the effect on mortality. The influence of SFN on the associated signaling pathways was analyzed using the interleukin 1ß (IL-1ß)-treated primary cultured rat hepatocytes. In the HIRI + PH-treated rats, SFN reduced serum liver enzyme activities and the frequency of pathological liver injury, such as apoptosis and neutrophil infiltration. SFN suppressed tumor necrosis factor-alpha (TNF-α) mRNA expression and inhibited nuclear factor-kappa B (NF-κB) activation by HIRI + PH. Mortality was significantly reduced by SFN. In IL-1ß-treated hepatocytes, SFN suppressed the expression of inflammatory cytokines and NF-κB activation. Taken together, SFN may have hepatoprotective effects in HIRI + PH in part by inhibiting the induction of inflammatory mediators, such as TNF-α, via the suppression of NF-κB in hepatocytes.

Hepatoprotection of a Standardized Extract of Cultured Lentinula edodes Mycelia against Liver Injury Induced by Ischemia-Reperfusion and Partial Hepatectomy.

A standardized extract of cultured Lentinula edodes mycelia (ECLM, AHCC®) has been shown to have beneficial effects on organ metabolism. ECLM has been indicated to have liver protective properties by suppressing inflammatory responses. The pathogenesis of hepatic ischemia-reperfusion injury is thought to involve the induction of inflammatory mediators. However, whether ECLM affects inflammatory mediators caused by warm hepatic ischemia-reperfusion injury and partial hepatectomy (HIRI+PH) has not been clarified. In this study, we evaluated the protective effects of ECLM against liver damage caused by HIRI+PH. Rats were fed a normal diet (HIRI+PH) or a normal diet with 2% ECLM (HIRI+PH and ECLM) for ten days, then the liver and duodenal ligament were clamped and subjected to 15 min of hepatic ischemia. After 70% hepatectomy, the inflow occlusion was released, and liver and blood samples were collected at 3, 6, and 24 h. The effect of ECLM on mortality induced by 30 min of ischemia and hepatectomy was evaluated. The results showed that ECLM attenuated pathological liver damage, including apoptosis, in the rats treated with HIRI+PH, and decreased serum aminotransferase activity; ECLM decreased mRNA levels of the inflammation-related genes inducible nitric oxide synthase and C-X-C motif chemokine ligand 1, and increased mRNA levels of interleukin 10, an anti-inflammatory cytokine; ECLM increased hepatocyte growth factor mRNA levels and Ki-67 labeled nuclei in the liver at 24 h; ECLM significantly reduced HIRI+PH-induced mortality. In conclusion, ECLM may prevent HIRI+PH-induced liver injury in part by suppressing various inflammatory responses and promoting liver regeneration.

COMBINATION THERAPY WITH A SENSE OLIGONUCLEOTIDE TO INDUCIBLE NITRIC OXIDE SYNTHASE MRNA AND HUMAN SOLUBLE THROMBOMODULIN IMPROVES SURVIVAL OF SEPSIS MODEL RATS AFTER PARTIAL HEPATECTOMY.

ABSTRACT: Sepsis after a major hepatectomy is a critical problem. In septic shock, the inflammatory mediator, nitric oxide (NO), is overproduced in hepatocytes and macrophages. The natural antisense (AS) transcripts, non-coding RNAs, are transcribed from a gene that encodes inducible nitric oxide synthase (iNOS). iNOS AS transcripts interact with and stabilize iNOS mRNAs. A single-stranded "sense oligonucleotide" (designated as SO1) corresponding to the iNOS mRNA sequence inhibits mRNA-AS transcript interactions and reduces iNOS mRNA levels in rat hepatocytes. In contrast, recombinant human soluble thrombomodulin (rTM) treats disseminated intravascular coagulopathy by suppressing coagulation, inflammation, and apoptosis. In this study, the combination therapy of SO1 and a low dose of rTM was evaluated for hepatoprotection in a rat septic shock model after partial hepatectomy. Rats underwent 70% hepatectomy, followed by intravenous (i.v.) injection of lipopolysaccharide (LPS) after 48 h. SO1 was injected (i.v.) simultaneously with LPS, whereas rTM was injected (i.v.) 1 h before LPS injection. Similarly to our previous report, SO1 increased survival after LPS injection. When rTM, which has different mechanisms of action, was combined with SO1, it did not interfere with the effect of SO1 and showed a significant increase in survival compared with LPS alone treatment. In serum, the combined treatment decreased NO levels. In the liver, the combined treatment inhibited iNOS mRNA and protein expression. A decreased iNOS AS transcript expression by the combined treatment was also observed. The combined treatment decreased mRNA expression of the inflammatory and pro-apoptotic genes while increasing that of the anti-apoptotic gene. Furthermore, the combined treatment reduced the number of myeloperoxidase-positive cells. These results suggested that the combination of SO1 and rTM has therapeutic potential for sepsis.

[A Case of Adenocarcinoma of Duct of Luschka].

A 75-year-old man was transferred to our hospital with a diagnosis of acute cholecystitis. On next day, a laparoscopic cholecystectomy was performed. Histologic examination confirmed an adenocarcinoma arising from duct of Luschka. Patient underwent additional resection of the liver bed. No residual adenocarcinoma was seen in the surgical specimen. Adenocarcinoma of duct of Luschka is rare, but it is important during cholecystectomy to consider the presence of duct of Luschka, possibility of malignant disease and careful dissection of the gallbladder from its fossa staying close to the gallbladder wall.

A case of undifferentiated carcinoma of the gallbladder with severe inflammation and difficult preoperative chemotherapy.

Undifferentiated carcinoma (UC) is relatively rare among gallbladder cancers, and the prognosis is poor compared to gallbladder adenocarcinoma. We report a 64-year-old man with gallbladder UC who underwent radical surgery and achieved long-term survival. He presented with a chief complaint of abdominal distension and loss of appetite. An abdominal computed tomography (CT) scan revealed a gallbladder tumor with a major axis of 120 mm that appeared to directly infiltrate the hepatic bed. No major vascular infiltration was noted, but the left and right intrahepatic bile ducts were dilated. On admission, the serum CRP level was 16.5 mg/dL; cholangitis and cholecystitis were suspected. He was hospitalized, treated with antibiotics, and underwent bile duct drainage; however, inflammation recurred and chemotherapy was not possible. Thus, three right liver areas, the caudate lobe, and the gallbladder were extirpated. Histopathologic examination showed a 130 × 90 mm tumor with extensive infiltration, hemorrhage, and necrosis in the liver. In the area occupied by the tumor, multinucleated cell proliferation, and polygonal and spindle-shaped tumor cells were noted. Based on the above findings, a diagnosis of UC was established. Postoperatively, gemcitabine and cisplatin were continued as adjuvant chemotherapy. No tumor recurrence has been detected after 24 months of follow-up care.

The Impact of Sorafenib in Combination with Intermittent Hepatic Arterial Infusion Chemotherapy for Unresectable Hepatocellular Carcinoma with Major Vascular Invasion.

The aim of the current study was to investigate the efficacy and safety of sorafenib and intermittent hepatic arterial infusion chemotherapy with cisplatin for unresectable hepatocellular carcinoma (HCC) with severe portal vein invasion. The antitumor effect was a complete response in 1 of 38 patients, a partial response in 12 patients, stable disease in 16 patients, and progressive disease in 9 patients, for a 34.2% response rate and a 76.3% disease control rate. This regimen had favorable efficacy and acceptable safety and may be feasible for unresectable HCC with severe portal vein invasion.

Long-term complete response to lenvatinib in a patient with unresectable hepatocellular carcinoma.

A 36-year-old man had been diagnosed with a solitary hepatocellular carcinoma in the right lobe of the liver by computed tomography, and right hemihepatectomy was performed 16 years previously. Approximately 13 years later, he underwent partial hepatectomy because of intrahepatic recurrence in segment 4. Multinodular intrahepatic recurrences in the remnant liver were identified 19 months after repeat hepatectomy, and he underwent transcatheter arterial chemoembolization therapy. Ultimately, six transcatheter arterial chemoembolization therapies were required because of multiple repeat multinodular intrahepatic recurrences. The patient was refractory to transcatheter arterial chemoembolization, and therefore, he participated in a trial of lenvatinib monotherapy. At lenvatinib initiation, his liver function was Child-Pugh class A. Enhanced abdominal computed tomography detected four tumors in the remnant liver. Enhanced abdominal computed tomography findings at the first evaluation showed no residual contrast uptake on arterial phase images, corresponding to a complete response according to Response Evaluation Criteria in Solid Tumors at 4 months after initiation of lenvatinib. The patient was able to continue long-term lenvatinib therapy with well-controlled general health, and he maintained a complete response for two years and three months. Here, we describe his clinical course and radiological results during lenvatinib monotherapy.

Investigation of a Tumor Location-Specific Therapeutic Strategy for Intrahepatic Cholangiocarcinoma.

OBJECTIVE: An optimal therapeutic strategy for intrahepatic cholangiocarcinoma (ICC) has not yet been determined. Herein we focused on intrahepatic tumor location and retrospectively analyzed tumor characteristics depending on location to elucidate a location-specific therapeutic strategy for ICC. METHODS: Sixty-five ICC patients were divided into three groups based on the distance between the innermost portion of the tumor and portal vein branches observed on preoperative imaging: peripheral, intermediate and central ICC. RESULTS: Median disease-specific survival (DSS) of the peripheral ICC was not reached, whereas median DSS was 32.9 months in intermediate ICC and 25.2 months in central ICC (p <0.05). Vascular invasion was observed in all groups (56-92%). Bile duct invasion to the first branch of the hepatic duct was more commonly observed in central ICC (43%) compared with the peripheral and intermediate ICC (0-8%). Lymph node metastasis was not observed in peripheral ICC, whereas it was frequently observed in intermediate and central ICC (39-44%). A Cox regression analysis revealed sufficient RDI (≥58.3%) of adjuvant chemotherapy (AC) significantly increased the length of DSS (HR: 0.205). Based on these data, we have proposed a location-specific therapeutic strategy as follows: peripheral ICC requires anatomical resection without lymphadenectomy; intermediate ICC requires anatomical resection with lymphadenectomy and sufficient doses of AC; and central ICC requires anatomical resection with extrahepatic bile duct resection, caudate lobectomy, lymphadenectomy, and sufficient doses of AC. CONCLUSION: We propose an intrahepatic tumor location-specific therapeutic strategy for ICC. This information could contribute to the appropriate therapeutic management of patients with ICC.

The Impact of Sorafenib in Combination with Transarterial Chemoembolization on the Outcomes of Intermediate-Stage Hepatocellular Carcinoma.

BACKGROUND: We investigated the treatment outcomes and hepatic reserve of transarterial chemoembolization (TACE)-refractory patients with recurrent advanced hepatocellular carcinoma (HCC) treated with TACE plus sorafenib. METHODS: Forty-one patients with intermediate-stage HCC defined as being TACE refractory on imaging were treated with sorafenib and TACE between 2009 and 2012 and comprised the combination treatment group. Twenty-nine patients who received repeated TACE after becoming refractory to TACE between 2005 and 2008 comprised the TACE continuation group. RESULTS: Although the interval between successive rounds of TACE was significantly shorter before the patients developed TACE refractoriness, it was significantly longer after the development of TACE refractoriness, in the combination treatment group compared with the TACE continuation group. The appearance of extrahepatic spread and/or vascular invasion differed significantly between the two groups. The median overall survival was significantly longer in the combination treatment group than in the TACE continuation group (20.5 vs. 15.4 months, respectively; hazard ratio = 2.04; 95% confidence interval = 1.20-3.48). The 3-year overall survival rate was 33.4% in the combination treatment group and 3.5% in the TACE continuation group. Downstaging of the Child-Pugh class was significantly less frequent in the combination treatment group than in the TACE continuation group. In COX proportional hazards analyses, sorafenib plus TACE resulted in a better prognosis compared with repeated TACE. CONCLUSIONS: Treatment with sorafenib plus TACE in TACE-refractory patients with intermediate-stage HCC resulted in longer intervals between TACE rounds, better maintenance of hepatic reserve, and significantly longer OS compared with repeated TACE.

Near-Infrared Fluorescence Imaging and Photodynamic Therapy for Liver Tumors.

Surgery with fluorescence equipment has improved to treat the malignant viscera, including hepatobiliary and pancreatic neoplasms. In both open and minimally invasive surgeries, optical imaging using near-infrared (NIR) fluorescence is used to assess anatomy and function in real time. Here, we review a variety of publications related to clinical applications of NIR fluorescence imaging in liver surgery. We have developed a novel nanoparticle (indocyanine green lactosome) that is biocompatible and can be used for imaging cancer tissues and also as a drug delivery system. To date, stable particles are formed in blood and have an ~10-20 h half-life. Particles labeled with a NIR fluorescent agent have been applied to cancer tissues by the enhanced permeability and retention effect in animals. Furthermore, this article reviews recent developments in photodynamic therapy with NIR fluorescence imaging, which may contribute and accelerate the innovative treatments for liver tumors.

Perioperative Geriatric Assessment as A Predictor of Long-Term Hepatectomy Outcomes in Elderly Patients with Hepatocellular Carcinoma.

This retrospective study recorded pertinent baseline geriatric assessment variables to identify risk factors for recurrence-free survival (RFS) and overall survival (OS) after hepatectomy in 100 consecutive patients aged ≥70 years with hepatocellular carcinoma. Patients had geriatric assessments of cognition, nutritional and functional statuses, and comorbidity burden, both preoperatively and at six months postoperatively. The rate of change in each score between preoperative and postoperative assessments was calculated by subtracting the preoperative score from the score at six months postoperatively, then dividing by the score at six months postoperatively. Patients with score change ≥0 comprised the maintenance group, while patients with score change <0 comprised the reduction group. The change in Geriatric 8 (G8) score at six months postoperatively was the most significant predictive factor for RFS and OS among the tested geriatric assessments. Five-year RFS rates were 43.4% vs. 6.7% (maintenance vs. reduction group; HR, 0.19; 95%CI, 0.11-0.31; p < 0.001). Five-year OS rates were 73.8% vs. 17.8% (HR, 0.12; 95%CI, 0.06-0.25; p < 0.001). Multivariate Cox proportional hazards analysis showed that perioperative maintenance of G8 score was an independent prognostic indicator for both RFS and OS. Perioperative changes in G8 scores can help forecast postoperative long-term outcomes in these patients.

New Hepatic Resection Criteria for Intermediate-Stage Hepatocellular Carcinoma Can Improve Long-Term Survival: A Retrospective, Multicenter Collaborative Study.

BACKGROUND: Hepatic resection (HR) is not recommended for intermediate-stage hepatocellular carcinoma (HCC) by the Barcelona Clinic Liver Cancer criteria. We examined the prognostic factors of HR for intermediate-stage HCC and developed new HR criteria for intermediate-stage HCC. METHODS: A total of 110 patients who underwent HR without any prior treatment for intermediate-stage HCC between January 2007 and December 2012 were enrolled at eight university hospitals. The outcomes and prognostic factors of HR were evaluated to develop new HR criteria. RESULTS: In terms of tumor size and number, the most significant prognostic factors were within the up-to-seven criteria. Furthermore, serum albumin level ≥35 g/L and serum alpha-fetoprotein (AFP) level.

Mortality analysis of Aeromonas hydrophila infection in hepato-biliary pancreatic surgery: Multicenter retrospective observational study.

BACKGROUND/PURPOSE: Aeromonas hydrophila can cause lethal infectious complications after surgery. There have been no large cohort studies of this specific to the hepato-biliary-pancreatic (HBP) field. We investigate the postoperative influence of A hydrophila infection after HBP surgery. METHODS: We retrospectively reviewed patients who underwent HBP surgery between 2008 and 2017 at eight university hospitals. Patients with A hydrophila isolation during perioperative management were extracted, and their postoperative courses were investigated. RESULTS: Bacterial culture examination of 10 074 patients was performed as perioperative management. Among them, 76 patients (0.75%) had A hydrophila isolation, most of whom underwent pancreatoduodenectomy (n = 38) or hepatectomy with biliary reconstruction (n = 14). There were seven mortalities after these two procedures (13.5%), five within 3 days after the onset of infection. Bile (n = 48) and abdominal drainage fluid (n = 29) were major sites of A hydrophila isolation. Typical prophylactic antibiotics, cefazolin or flomoxef, were mostly resistant. There was no mortality among patients that received sensitive antibiotics prophylactically. CONCLUSIONS: Isolation of A hydrophila was low in our cases of HBP surgery, but the condition of some patients deteriorated rapidly by this infection. Although there could be several bacterial infections during management of HBP surgery, A hydrophila should not be overlooked. Preparation of appropriate prophylactic antibiotics may prevent or reduce mortality.

Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients: a multi-centre propensity score-based analysis.

BACKGROUND: The frequency of liver resection in elderly patients has been increasing. However, data are limited regarding the safety of laparoscopic liver resection (LLR) compared with that of open liver resection (OLR) for hepatocellular carcinoma (HCC) in elderly patients. The present study aimed to compare short-term outcomes between LLR and OLR in elderly patients with HCC using propensity score matching. METHODS: The study included 630 patients (age, ≥ 75 years) who underwent liver resection for HCC at nine liver centres between April 2010 and December 2017. Patients were divided into LLR and OLR groups, and perioperative outcomes were compared between the groups. In addition, subgroup analysis was performed according to age (75-79 and ≥ 80 years). RESULTS: Of the 630 patients, 221 and 409 were included in the LLR and OLR groups, respectively. After propensity score matching, 155 patients were included in each group. Intraoperative blood loss and the transfusion, post-operative overall complication and major complication rates were lower in the matched LLR than the matched OLR group (P < 0.001, P = 0.004, P < 0.001 and P < 0.001, respectively). Moreover, post-operative pulmonary and cardiovascular complications were less frequent in the matched LLR group (P = 0.008 and P = 0.014, respectively). In subgroup analysis, among octogenarians, the post-operative major complication rate was lower and hospital stay was shorter in the matched LLR than the matched OLR group (P < 0.001 and P < 0.001, respectively). CONCLUSION: LLR for HCC is associated with good short-term outcomes in patients aged ≥ 75 years compared with OLR. LLR is safe and feasible in selected octogenarians with HCC.

Perioperative exercise capacity in chronic liver injury patients with hepatocellular carcinoma undergoing hepatectomy.

Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. We aimed to clarify whether perioperative exercise capacity was related to long-term survival in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy. One hundred-six patients with hepatocellular carcinoma underwent pre- and postoperative cardiopulmonary exercise testing to determine their anaerobic threshold, defined as the point between carbon dioxide production and oxygen consumption per unit of time. Testing involved 35 items including blood biochemistry analysis, in-vivo component analysis, dual-energy X-ray absorptiometry, and cardiopulmonary exercise testing preoperatively and 6 months postoperatively. We classified patients with anaerobic threshold ≥ 90% 6 months postoperatively compared with the preoperative level as the maintenance group (n = 78) and patients with anaerobic threshold < 90% as the decrease group (n = 28). Five-year recurrence-free survival rates were 39.9% vs. 9.9% (maintenance vs. decrease group) (hazard ratio: 1.87 [95% confidence interval: 1.12-3.13]; P = 0.018). Five-year overall survival rates were maintenance: 81.9%, and decrease: 61.7% (hazard ratio: 2.95 [95% confidence interval: 1.37-6.33]; P = 0.006). Multivariable Cox proportional hazards models showed that perioperative maintenance of anaerobic threshold was an independent prognostic indicator for both recurrence-free- and overall survival. Although the mean anaerobic threshold from preoperative to postoperative month 6 decreased in the exercise-not-implemented group, the exercise-implemented group experienced increased anaerobic threshold, on average, at postoperative month 6. The significant prognostic factor affecting postoperative survival for chronic liver injury patients with HCC undergoing hepatectomy was maintenance of anaerobic threshold up to 6 months postoperatively.

The Proton Pump Inhibitor Lansoprazole Has Hepatoprotective Effects in In Vitro and In Vivo Rat Models of Acute Liver Injury.

BACKGROUND/AIMS: The proton pump inhibitor lansoprazole (LPZ) is clinically used to reduce gastric acid secretion, but little is known about its possible hepatoprotective effects. This study aimed to investigate the hepatoprotective effects of LPZ and its potential mechanisms using in vitro and in vivo rat models of liver injury. METHODS: For the in vitro model of liver injury, primary cultured rat hepatocytes were treated with interleukin-1ß in the presence or absence of LPZ. The influence of LPZ on inducible nitric oxide synthase (iNOS) induction and nitric oxide (NO) production and on the associated signaling pathways was analyzed. For the in vivo model, rats were treated with D-galactosamine (GalN) and lipopolysaccharide (LPS). The effects of LPZ on survival and proinflammatory mediator expression (including iNOS and tumor necrosis factor-α) in these rats were examined. RESULTS: LPZ inhibited iNOS induction partially through suppression of the nuclear factor-kappa B signaling pathway in hepatocytes, thereby reducing potential liver injury from excessive NO levels. Additionally, LPZ increased survival by 50% and decreased iNOS, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractant-1 mRNA expression in the livers of GalN/LPS-treated rats. LPZ also inhibited nuclear factor-kappa B activation by GalN/LPS. CONCLUSIONS: LPZ inhibits the induction of several inflammatory mediators (including cytokines, chemokines, and NO) partially through suppression of nuclear factor-kappa B, resulting in the prevention of fulminant liver failure. The therapeutic potential of LPZ for liver injuries warrants further investigation.

Efficacy of a third-generation oncolytic herpes simplex virus in neuroendocrine tumor xenograft models.

BACKGROUND: Few chemotherapies are available for neuroendocrine tumors, especially for highly malignant neuroendocrine cancers. The third-generation oncolytic herpes simplex virus type 1 (HSV-1) T-01 selectively replicates in tumor cells and shows cytotoxicity against tumor cells without damaging surrounding normal tissues. We examined the antitumor effect of T-01 to explore novel treatments for patients with neuroendocrine tumors. METHODS: The cytotoxicity of T-01 was tested in two human and one murine neuroendocrine tumor cell lines in vitro. Mouse models with subcutaneously implanted human neuroendocrine tumor QGP1 cells were used to investigate T-01 efficacy in vivo. RESULTS: T-01 showed cytotoxicity against the three cell lines in vitro. In xenograft models, the growth of tumors derived from QGP1 cells was inhibited by T-01 compared with control group. Although weight loss of mice was observed with tumor growth in the control group, it was suppressed by T-01 administration. The antitumor effects of T-01 were dependent on virus concentration and frequency of administration. CONCLUSIONS: T-01 effectively inhibits tumor cell proliferation in a poorly differentiated NEC mouse model. These results suggest that the third-generation oncolytic HSV-1 may serve as a novel treatment for patients with neuroendocrine tumors.