High-Mobility Group Box 1 expression predicts survival of patients after resection of adenocarcinoma of the ampulla of Vater.

BACKGROUND: Expression of High-Mobility Group Box 1 (HMGB1), a multifunctional protein involved in DNA function as well as cell proliferation, inflammation, and the immune response, has been reported to be prognostic in several types of malignancies. However, the prognostic value of HMGB1 in ampullary cancer has not been studied. METHODS: Patients with adenocarcinoma of the ampulla of Vater who underwent R0 resection with pancreaticoduodenectomy between 2001 and 2011 were included in the present multi-institutional study. The degree of HMGB1 expression was examined in each resected specimen by immunohistochemical staining. RESULTS: A total of 101 patients were enrolled of which, 79 patients were eligible. High expression of HMGB1 was observed in 31 (39%) patients. Blood loss, transfusion, tumor stage, nodal status, and HMGB1 expression were identified as predictors with univariate analysis. Multivariate analysis showed that transfusion, lymph-node metastasis, and high HMGB1 expression were independent predictors of poor overall survival. Subgroup analysis showed that high HMGB1 expression was predictive, especially in patients who did not receive adjuvant chemotherapy. CONCLUSIONS: High HMGB1 expression is an independent predictor of poor prognosis in patients with adenocarcinoma of the ampulla of Vater not treated with adjuvant chemotherapy.

Incidence and risk factors for rectovaginal fistula after low anterior resection for rectal cancer.

BACKGROUND: The rectovaginal fistula (RVF) is a rare complication after low anterior resection (LAR) for rectal cancer. The aim of this study was to evaluate the risk factors for RVF after LAR for rectal cancer. METHODS: This was a retrospective multi-institution study of 371 female rectal cancer patients who underwent LAR with anastomosis between January 2007 and December 2011. Patient-, tumor-, and surgery-related variables were examined by univariate and multivariate analyses. RESULTS: The overall RVF rate was 3.0 % (11/371). The RVF was diagnosed on median postoperative day 83 (15-766). In 81.8 % (9/11) of the patients, the diagnosis of RVF was made after hospital discharge. Multivariate analysis identified prognostic nutritional index (PNI; odds ratio (OR) 6.97; 95 % confidence interval (CI) 1.47-33.08; P = 0.015), preoperative chemotherapy (OR 27.31; CI 3.49-213.62; P = 0.002), tumor size (OR 5.90; CI 1.04-33.47; P = 0.045), intraoperative bleeding (OR 13.91; CI 1.34-144.42; P = 0.027), and lateral lymph node dissection (OR 4.92; CI 1.02-23.63; P = 0.045) as independent risk factors for RVF after LAR. CONCLUSIONS: Risk factors of RVF were PNI (<45), preoperative chemotherapy, tumor size (≧ 50 mm), intraoperative bleeding (≧ 200 ml), and lateral lymph node dissection. Before an operation, obtaining the information about these risk factors is of great importance in LAR for rectal cancer.

Role of transforming growth factor-beta1 (TGF-beta1) in endotoxin-induced hepatic failure after extensive hepatectomy in rats.

Postoperative infections after hepatectomy sometimes lead to fatal hepatic failure, but the mechanism of the hepatic failure is unclear. Wistar rats underwent 90% hepatectomy, and were then divided into three groups: (i) the SAL group, injected with normal saline; (ii) the LPS group, injected with lipopolysaccharide (LPS) every day for 1 week; and (iii) the LPS plus TGF-Ab (LPS+TGF-Ab) group, injected with LPS with anti-transforming growth factor-beta1 (TGF-beta1) antibody. We investigated survival rates, TGF-beta1 expression in the liver, liver regeneration by proliferating cell nuclear antigen labeling index, hepatocyte apoptosis by single stranded DNA labeling index, and perisinusoidal fibrosis using Masson's trichrome staining. The LPS group (30.4%) had a significantly lower survival rate than the SAL group (84%) and tended to be lower than the LPS+TGF-Ab group (49.4%). Liver regeneration in the LPS group was significantly lower than in the other groups. In the LPS group, hepatocyte apoptosis and perisinusoidal fibrosis was significantly more remarkable, and TGF-beta1 expression was significantly higher than in the SAL group. TGF-beta1 enhanced by LPS plays an important role in the mechanism of hepatic failure by infections after hepatectomy, especially in inhibition of liver regeneration, and induction of hepatocyte apoptosis and perisinusoidal fibrosis.

Extended abdominoperineal resection with partial prostatectomy for T3 rectal cancer.

BACKGROUND/AIMS: To describe and discuss extended abdominoperineal resection with partial prostatectomy using the ultrasonic harmonic scalpel as an alternative to total pelvic exenteration in lower rectal T3 cancer contiguous with the prostate. METHODOLOGY: Extended abdominoperineal resection with partial prostatectomy was performed in 4 patients with lower rectal clinical stage T3 cancer contiguous with the prostate using the ultrasonic harmonic scalpel. The ultrasonic harmonic scalpel permitted en bloc dissection of the rectum and the posterior part of the prostate, removing all tumor and disruption of the normal urinary stream. RESULTS: Blood loss ranged from 600 to 2500 mL. The final pathologic stage was T2 in 1, T3 in 2 and T4 in 1 patient, and the surgical margins were clear in all patients. Urethral injury occurred in 1 patient, and 2 patients had postoperative urinary dysfunction. No patients required a urinary stoma or suffered recurrence. CONCLUSIONS: Extended abdominoperineal resection with partial prostatectomy using the ultrasonic harmonic scalpel is an attractive alternative to total pelvic exenteration for patients with lower rectal T3 cancer contiguous with the prostate.

Mechanism of postoperative liver failure after excessive hepatectomy investigated using a cDNA microarray.

BACKGROUND/PURPOSE: Excessive hepatectomy often causes fatal liver failure. We have reported that this is mainly mediated by apoptosis, characterized pathologically by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) assay-positive hepatocytes and a ladder pattern in DNA fragmentation assays. METHODS: To investigate the mechanism, we used cDNA microarray analysis to compare clearly differentiated rat partial hepatectomy (PHx) models (90% PHx, and 95% PHx). All 90% PHx rats survived, but the 95% PHx animals died of hepatic failure within 96 h. Remnant liver was obtained at four time points (1, 3, 12, and 24 h after PHx). After RNA extraction, two samples were labeled with different fluorescent dyes and hybridized to the Institute of Physical and Chemical Research (RIKEN) set of 18 816 full-length enriched mouse cDNA arrays. Scanning for fluorescent dye signals was performed, and the mRNA expression ratio of the two models was examined. RESULTS: Genes of the p21 cyclin-dependent kinase (CDK) inhibitor, Fas, interleukin (IL)-18, and many caspases were upregulated at 1 h after PHx in the 95% PHx group. On the other hand, genes of Bcl-2, heat shock proteins, and glutathione-S-transferase were downregulated. CONCLUSIONS: We concluded that fatal hepatic failure after excessive hepatectomy was characterized by increased apoptosis and diminished liver regeneration.