Prognostic value of systemic inflammation score in patients with esophageal cancer.

Introduction: The systemic inflammatory score (SIS), a new inflammatory marker based on a combination of the lymphocyte-to-monocyte ratio (LMR) and serum albumin concentration, has been reported to be a useful prognostic marker for several malignancies. The authors conducted this retrospective study on data from a cohort of esophageal cancer patients undergoing potentially curative resection to clarify the value of SIS as a prognostic marker for clinical outcome in this population. Methods: This retrospective cohort study included 32 patients who underwent thoracoscopic esophagectomy after neoadjuvant chemotherapy for esophageal cancer between January 2016 and December 2019. Blood samples were collected within one week prior to the initiation of preoperative chemotherapy. Three inflammatory and nutritional markers; SIS, the neutrophil-to-lymphocyte ratio (NLR), and prognostic nutrition index (PNI) were examined in this study. Disease-free survival was assessed using the Kaplan-Meier method, and univariable and multivariable Cox models were applied to evaluate the predictive value of SIS, NLR and PNI. Results: NLR and PNI were not associated with recurrence, while SIS scores of 1 and 2 were significantly associated with recurrence. In multivariate analysis, SIS scores of 1 or 2 were found to be independently associated with recurrence, each with a hazard ratio of 1.98. In addition, when examining immunologic and nutritional factors and survival rates, there was no significant difference in the survival rate for NLR and PNI; for SIS, however, the survival rate was significantly worse in patients with SIS scores of 1 or 2. Conclusions: The authors demonstrated that a novel and easily obtained prognostic score, termed SIS, based on pre-treatment serum albumin and LMR, can serve as an independent prognostic factor in postoperative esophageal cancer patients. It could be incorporated into conventional clinical and pathological algorithms to enhance the prognostic accuracy in this population.

Primary Malignant Melanoma of the Esophagus Treated with Surgical Resection at an Early Stage.

Introduction: Primary malignant melanoma of the esophagus is a very rare disease with a poor prognosis. We herein report a patient with primary malignant melanoma of the esophagus who underwent surgical resection. Case Presentation: A 73-year-old female underwent an upper gastrointestinal endoscopy during follow-up for colonic diverticulitis. An endoscopic examination and constructed radiography revealed a slightly elevated black pigmented lesion in the upper esophagus and a black pigmented area in the esophagogastric junction. Through a preoperative endoscopic biopsy, she was diagnosed with malignant melanoma of the esophagus. We performed thoracoscopy-assisted and laparoscopy-assisted subtotal esophagectomy with lymphadenectomy. The surgical specimens were subjected to immunohistochemical analysis, resulting in a diagnosis of malignant melanoma. The tumor cells were positive for Melan-A and HMB-45 diffusely, supporting that diagnosis. We performed surgical resection in a case of primary malignant melanoma of the esophagus, and the patient has remained disease free for 2 years since the surgery. Conclusion: Early diagnosis and radical resection may be essential for long-term survival in patients with malignant melanoma of the esophagus.

Low-dose recombinant human hepatocyte growth factor enhances effect of hepatocyte transplantation in rats treated with retrorsine.

BACKGROUND/AIMS: The aim of this study was to regenerate transplanted hepatocytes selectively in a recipient using retrorsine and recombinant human hepatocyte growth factor (rhHGF). METHODOLOGY: Nagase analbuminemic rats (NARs) received pretreatment with retrosine and were divided into three experimental groups. Group1: Hepatocyte transplantation (HcTx) + 50 microg/kg/day rhHGF. Group2: HcTx + 250 microg/kg/day rhHGF. Group3: HcTx + normal saline. The serum levels of albumin and the albumin-positive hepatocytes in the liver were investigated. The rat endogenous HGF of the rats given only retrorsine was measured. RESULTS: The serum albumin levels of Group11 were higher than those of Group2, while there was no significant difference between Group2 and GroupS. Histological examination of Group1 and 3 showed the presence of a large number of albumin-positive hepatocytes, which frequently consisted of large clusters and occupied 53.90 +/- 2.31% and 31.25 +/- 5.36% of host liver, respectively. The liver sections of Group2 showed numerous albumin-positive hepatocyte, which were not seen as clusters. The rat endogenous HGF concentration was extremely high. CONCLUSION: Low-dose rhHGF enhances the effect of HcTx under the suppressive state of proliferation of host hepatocytes. Because of the high endogenous HGF, the administration of a high concentration of rhHGF suppressed the regenerative activity of the transplanted hepatocytes.

Comparison between bioartificial and artificial liver for the treatment of acute liver failure in pigs.

AIM: To characterize and evaluate the therapeutic efficacy of bioartificial liver (BAL) as compared to that of continuous hemodiafiltration (CHDF) with plasma exchange (PE), which is the current standard therapy for fulminant hepatic failure (FHF) in Japan. METHODS: Pigs with hepatic devascularization were divided into three groups: (1) a non-treatment group (NT; n = 4); (2) a BAL treatment group (BAL; n = 4), (3) a PE + CHDF treatment group using 1.5 L of normal porcine plasma with CHDF (PE + CHDF, n = 4). Our BAL system consisted of a hollow fiber module with 0.2 mum pores and 1 multiply 10(10) of microcarrier-attached hepatocytes inoculated into the extra-fiber space. Each treatment was initiated 4 h after hepatic devascularization. RESULTS: The pigs in the BAL and the PE + CHDF groups survived longer than those in the NT group. The elimination capacity of blood ammonia by both BAL and PE + CHDF was significantly higher than that in NT. Aromatic amino acids (AAA) were selectively eliminated by BAL, whereas both AAA and branched chain amino acids, which are beneficial for life, were eliminated by PE + CHDF. Electrolytes maintenance and acid-base balance were better in the CPE + CHDF group than that in the BAL group. CONCLUSION: Our results suggest that PE + CHDF eliminate all factors regardless of benefits, whereas BAL selectively metabolizes toxic factors such as AAA. However since PE + CHDF maintain electrolytes and acid-base balance, a combination therapy of BAL plus CPE + CHDF might be more effective for FHF.

Changes in serum levels of hepatocyte growth factor in patients undergoing adult-to-adult living-donor liver transplantation.

Changes in the serum concentration of hepatocyte growth factor (HGF), a potent mitogen for hepatocytes, were investigated in adult-to-adult living-donor liver transplantation (LDLT) in which liver regeneration is involved. Between August 2000 and November 2002, 15 consecutive adult-to-adult LDLTs were performed using the right lobe graft. The recipients were divided into two groups: acute liver failure (n=6) and chronic liver failure (n=9). In addition, right lobe donors (n=12) were evaluated. Measurement of HGF was performed on preoperative and postoperative days 1, 3, 7, and 14 after LDLT. The pretransplant levels of serum HGF were higher in the acute liver failure group than in the chronic liver failure group (P<0.05). After liver replacement, serum HGF levels normalized rapidly in both groups and remained rather low. Despite vigorous liver regeneration in all groups, serum HGF levels did not change significantly after adult-to-adult LDLT with right lobe graft.

Relationship between portal venous flow and liver regeneration in patients after living donor right-lobe liver transplantation.

The purpose of this study is to evaluate the relationship between portal venous (PV) velocity and degree of liver regeneration in humans after living donor liver transplantation (LDLT). Between July 1997 and September 2002, a total of 15 adult-to-adult LDLTs with right-lobe grafts were performed, and 13 of these patients were enrolled in this study. Postoperative PV dynamics differed according to the primary liver disease; therefore, patients were divided into two groups: a fulminant hepatic failure (FHF) group (n = 4) and a liver cirrhosis (LC) group (n = 9). Right-lobe donors (n = 13; D group) were used as controls. Doppler ultrasound was used to measured changes in PV velocity preoperatively; postoperative days (PODs) 1, 3, 7, 14, and 28; and 3 months after LDLT. To assess hepatic regeneration, the increase in liver volume ratio (postoperative liver volume to standard liver volume [SLV]) was measured. PV velocity after LDLT in the LC group increased sharply until POD 7, whereas those in the FHF and D groups were constant. In the first 3 months after LDLT, mean PV velocity was greater in the LC group than the other groups, reflecting the persistent hyperdynamic state in chronic end-stage liver disease. Liver regeneration also was more rapid in the LC group than the FHF and D groups and reached 100% as early as 2 weeks posttransplantation, whereas both the FHF and D livers reached approximately 80% of SLV at 3 months. PV velocity POD 7 correlated significantly with regeneration of the partial-liver allograft at 1 month (r = 0.84; P =.0091). In conclusion, the PV persistent hyperdynamic state in the LC group could directly trigger early liver regeneration in partial-liver allografts after LDLT.

Video-assisted neck surgery for thyroid and parathyroid diseases.

BACKGROUND: Endoscopic surgery has now become a well-established modality for the treatment of various organ diseases. In the present study, we analyzed the surgical results achieved by video-assisted neck surgery (VANS) in thyroid and parathyroid diseases. METHODS: From January 2000 to April 2002, 87 patients (eight males and 79 females) with a mean age of 49 years underwent VANS. The preoperative diagnoses of these patients included 37 benign thyroid tumors, 30 Graves' diseases, 17 parathyroid adenomas and three thyroid cancers. RESULTS: The mean operative time of VANS was 165 min for a hemithyroidectomy, 287 min for a subtotal thyroidectomy, and 157 min for a parathyroidectomy. The mean intraoperative blood loss was 60, 183 and 23 g for a hemithyroidectomy, subtotal thyroidectomy and parathyroidectomy, respectively. No conversion from VANS to conventional surgery was experienced. Three patients (3.4%) had temporary palsy of the recurrent laryngeal nerve. Otherwise, the postoperative courses were uneventful. CONCLUSIONS: VANS for thyroid and parathyroid diseases was found to be safe and effective. From a cosmetic point of view, a high degree of patient satisfaction was obtained. VANS is thus considered to be an excellent option for selected patients with thyroid and parathyroid diseases.

Intrasplenic transplantation of encapsulated cells: a novel approach to cell therapy.

Cell therapy is likely to succeed clinically if cells survive at the transplantation site and are protected against immune rejection. We hypothesized that this could be achieved with intrasplenic transplantation of encapsulated cells because the cells would have instant access to oxygen and nutrients while being separated from the host immune system. In order to provide proof of the concept, primary rat hepatocytes and human hepatoblastoma-derived HepG2 cells were used as model cells. Rat hepatocytes were encapsulated in 100-kDa hollow fibers and cultured for up to 28 days. Rat spleens were implanted with hollow fibers that were either empty or contained I x 10(7) rat hepatocytes. Human HepG2 cells were encapsulated using alginate/ poly-L-lysine (ALP) and also transplanted into the spleen; control rats were transplanted with free HepG2 cells. Blood human albumin levels were measured using Western blotting and spleen sections were immunostained for albumin. Hepatocytes in monolayer cultures remained viable for only 6-10 days, whereas the cells cultured in hollow fibers remained viable and produced albumin throughout the study period. Allogeneic hepatocytes transplanted in hollow fibers remained viable for 4 weeks (end of study). Free HepG2 transplants lost viability and function after 7 days, whereas encapsulated HepG2 cells remained viable and secreted human albumin at all time points studied. ALP capsules, with or without xenogeneic HepG2 cells, produced no local fibrotic response. These data indicate that intrasplenic transplantation of encapsulated cells results in excellent survival and function of the transplanted cells and that the proposed technique has the potential to allow transplantation of allo- and xenogeneic cells (e.g., pancreatic islets) without immunosuppression.

Immediate early genes and p21 regulation in liver of rats with acute hepatic failure.

It has been observed that liver regeneration in acute hepatic failure (AHF) is suppressed [Eguchi et al. Hepatology 1996;24(6):1452-9]. The molecular mechanism regulating this inhibition is not known. We previously reported that in AHF rats, hepatocyte proliferation was significantly impaired with elevation in serum IL-6, TGF-beta1, and HGF [Kamohara et al. Biochem Biophys Res Commun 2000;273(1):129-35]. Following either 70% partial hepatectomy (PH) or liver injury, quiescent mature hepatocytes are "primed" to re-enter the cell cycle. The process of "priming" appears to be triggered by extracellular cytokines (IL-6 and TNF-alpha) and is characterized by expression of immediate early genes. Under the stimulation of growth factors such as HGF, "primed" hepatocytes exit the G1 phase of the cell cycle. G1-associated cyclins and their inhibitors play a pivotal role in G1/S cell cycle transition. Here, we demonstrate that immediate early gene (i.e. c-myc, c-fos) expression and AP-1 activity are preserved in AHF rat livers despite absence of hepatocyte proliferation. In contrast, p21 mRNA and protein are both over-expressed in AHF livers compared to livers from rats undergoing PH; this elevation leads to inhibition in Cdk2 activity, resulting in G1 cell cycle arrest and inhibition of regeneration.

Glycerol suppresses proliferation of rat hepatocytes and human HepG2 cells.

BACKGROUND: In fulminant hepatic failure (FHF), the ability of surviving hepatocytes to proliferate is diminished. Therefore, it is important that medical therapy cause no further impairment of liver regeneration. In FHF, intracranial hypertension secondary to brain edema is the most common cause of brain injury and death and glycerol is used in some countries to treat this complication. Glycerol has been long known to suppress the growth of various cell types. We therefore decided to examine the effect of glycerol on hepatocyte proliferation in vitro and in vivo in rats subjected to partial (2/3) hepatectomy. Additionally, we investigated the effect of glycerol on the proliferation of HepG2 cells. MATERIALS AND METHODS: Mitogen-induced primary rat hepatocytes were cultured in a hormonally defined Dulbecco's modified Eagle's medium containing increasing amounts of glycerol (0.5, 1.0, 2.0, 4.0%). HepG2 cells were cultured in minimal essential medium/10% FBS. After 2 days, HepG2 cells were exposed to glycerol (1.0-2.0-4.0%) and harvested after 48 h. Control dishes contained no glycerol. Cell proliferation was measured by the incorporation of [(3)H]thymidine and/or bromodeoxyuridine (BrdU). In vivo, Sprague-Dawley rats were subjected to standard partial 2/3 hepatectomy and assigned to intraportal administration of either 400 microl of glycerol or saline. Rats were killed after 1, 2, 3, 5, and 7 days. Liver weight/body weight ratio and BrdU uptake were measured. RESULTS: In all cultures tested, glycerol suppressed the growth of cells in a dose-dependent manner. In vivo, a single intraportal dose of glycerol slowed the liver regenerative response. CONCLUSIONS: This study demonstrated that glycerol has a potent growth-inhibitory effect on hepatocyte proliferation in vivo and in vitro. Remarkably, glycerol inhibited the proliferation of liver cancer cells as well. The results of this study have important clinical implications.

Hepatic expression and serum levels of thrombomodulin reflect the extent of liver injury in rats with fulminant hepatic failure and extensive hepatectomy.

In order to evaluate the biological significance of thrombomodulin (TM) in the serum and its expression in the liver, changes in TM were investigated in rats with fulminant hepatic failure (FHF) or after extensive hepatectomy. Forty-two rats were divided into four groups as follows: control (sham, n=6), 70% hepatectomy (70% Hx, n=12), 90% hepatectomy (90% Hx, n=12) and fulminant hepatic failure (FHF, n=12). The soluble-TM levels in the 90% Hx and FHF groups were significantly higher than that in the 70% Hx group. In the FHF group, the soluble-TM level 24 h after induction was significantly higher than that at 12 h (P<0.05). Moreover, the level of soluble TM was significantly higher in the FHF group than that in the 90% Hx group, while hyaluronic acid was not increased at statistical significance. The expression of TM in the liver intensified with time in both FHF and 90% Hx groups, which was more pronounced in zone 3 of the liver in FHF group than in the 90% Hx group. In conclusion, elevation of s-TM in the serum and expression of TM in the sinusoidal endothelial cell are useful markers of hepatic failure and its sinusoidal endothelial injury, especially in the state of FHF, since the presence of necrotic liver tissue is the only difference between FHF and 90% Hx in the model of the rats.