Aiichiro Higure

Recombinant human soluble thrombomodulin decreases the plasma high-mobility group box-1 protein levels, whereas improving the acute liver injury and survival rates in experimental endotoxemia.

Objective: In addition to the hyperactivation of the inflammatory cytokines, high-mobility group box-1 protein (HMGB1), recently identified as a lethal late-phase mediator is suspected to be closely correlated with the development of sepsis. Therefore, the therapeutic efficacy of recombinant human soluble thrombomodulin (ART-123) administration on the production of inflammatory cytokines and the plasma level of HMGB1 was investigated in experimental endotoxemia. Design: Prospective, comparative, experimental study. Setting: Laboratory animal research center at a university. Subjects: Male Sprague-Dawley rats (250–300 g). Interventions: Endotoxemia was induced in rats by a bolus intravenous injection of lipopolysaccharide (LPS) at a dosage of 4 mg/kg (LPS group). ART-123 (1 mg/kg) was administered as a bolus injection 30 minutes before or 4 hours after injection of LPS (ART-123 pretreated/treated group). As a control, an equal volume of physiologic saline was administered instead of LPS and ART-123 (control group). Measurements and Main Results: Rats were randomly divided into ART-123 pretreated group, ART-123 treated group, and LPS group, respectively. After the injection of LPS, the levels of inflammatory cytokines and thrombin–antithrombin III complex, plasma HMGB1 concentrations, liver immunohistochemical and histopathologic characteristics, liver dysfunction, and survival rate were examined. The increased levels of inflammatory cytokines and plasma HMGB1 induced by LPS in this rat model were improved by the administration of ART-123; additionally, reduced liver dysfunction and increased survival rate were observed. Conclusions: This study demonstrated that ART-123 inhibits the expression of inflammatory cytokines and decreases the plasma HMGB1 levels in experimental endotoxemia. In addition, ART-123 administration markedly reduced liver dysfunction and mortality even with delayed treatment of ART-123. The use of ART-123 may therefore be a beneficial treatment for septic patients.

Midkine protects hepatocellular carcinoma cells against TRAIL-mediated apoptosis through down-regulation of caspase-3 activity

It is believed that midkine (MK), a heparin‐binding growth factor, plays an important role in carcinogenesis. However, the biologic mechanism of MK in hepatocellular carcinoma has not been clarified to date. The objective of the current study was to investigate the antiapoptotic role of MK in a human hepatoma cell line.

Risk factors for a prolonged operative time in a single-incision laparoscopic cholecystectomy

BACKGROUND A prolonged operative time is associated with adverse post-operative outcomes in laparoscopic surgery. Although a single-incision laparoscopic cholecystectomy (SILC) requires a longer operative time as compared with a conventional laparoscopic cholecystectomy, risk factors for a prolonged operative time in SILC remain unknown. METHODS A total of 20 clinical variables were retrospectively reviewed to identify factors for a prolonged operative time (longer than 3 h) in a total of 220 consecutive patients undergoing SILC. RESULTS The median operative time was 145 min (range, 55-435) and a prolonged operative time was required in 62 patients (28%). Independent factors that predict a prolonged operative time as identified through multivariate analysis were body mass index (BMI) (P = 0.009), acute cholecystitis (P < 0.001) and operator (resident or staff surgeon) (P < 0.001). Furthermore, a prolonged operative time was significantly associated with an increased amount of intra-operative blood loss (P < 0.001) and a prolonged stay after surgery (P < 0.001). CONCLUSIONS These findings suggest that a higher BMI, acute cholecystitis and a resident as an operator significantly increase the duration of SILC procedures.

Malignant hemangiopericytoma in the pelvic cavity successfully treated by combined-modality therapy: report of a case.

A 55-year-old Japanese woman underwent extirpation of a malignant hemangiopericytoma in the pelvic cavity, followed by postoperative irradiation. An abdominal computed tomography scan 3 years later revealed a local recurrent tumor, 12 cm in diameter, in the pelvic cavity, for which transarterial embolization was done, followed by excision of the tumor employing Hartmanns procedure. Although an unresectable part of the recurrent tumor remained, postoperative irradiation reduced its size remarkably. The patient is still alive 7 years 2 months after her first operation, but with more recurrent tumors in the abdominal wall and around the bilateral iliac arteries. Because hemangiopericytoma often recurs or metastasizes after a prolonged disease-free interval, close long-term follow-up is necessary after the operation. Combined-modality therapy against the recurrent or unresectable disease may result in a good prognosis.

A novel epigenetic mechanism regulating hyaluronan production in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma enriched with hyaluronan (HA), a major component of extracellular matrix known to play a critical role in tumor progression. The mechanisms that regulate HA synthesis in PDAC are poorly understood. To investigate whether DNA methylation and HA production from PDAC cells are associated, we studied the effect of 5-aza-2′-deoxycitidine (5-aza-dC), an inhibitor of DNA methylation, or DNA methyltransferase 1 (DNMT1) knockdown by small interfering RNA, on the HA production from PDAC cells. HA production into the conditioned medium was evaluated in PDAC cells treated with 5-aza-dC or DNMT1 knockdown. mRNA expression of HA synthase (HAS) genes was investigated by real-time RT-PCR. Treatment of PDAC cells with 5-aza-dC led to a significant increase in the HA production (up to 2.5-fold increase) in all 4 cell lines tested. This enhanced HA production by 5-aza-dC treatment was accompanied by increased mRNA expression of HAS2 and HAS3. Furthermore, increased HA production and HAS2/HAS3 mRNA expression was also observed in PDAC cells by knockdown of DNMT1. These findings provide evidence, for the first time, that epigenetic mechanism is involved in the regulation of HA synthesis in PDAC cells.

Stapled gastro/duodenojejunostomy shortens reconstruction time during pylorus-preserving pancreaticoduodenectomy

AIM To investigate whether a stapled technique is superior to the conventional hand-sewn technique for gastro/duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy (PpPD). METHODS In October 2010, we introduced a mechanical anastomotic technique of gastro- or duodenojejunostomy using staplers during PpPD. We compared clinical outcomes between 19 patients who underwent PpPD with a stapled gastro/duodenojejunostomy (stapled anastomosis group) and 19 patients who underwent PpPD with a conventional hand-sewn duodenojejunostomy (hand-sewn anastomosis group). RESULTS The time required for reconstruction was significantly shorter in the stapled anastomosis group than in the hand-sewn anastomosis group (186.0 ± 29.4 min vs 219.7 ± 50.0 min, P = 0.02). In addition, intraoperative blood loss was significantly less (391.0 ± 212.0 mL vs 647.1 ± 482.1 mL, P = 0.03) and the time to oral intake was significantly shorter (5.4 ± 1.7 d vs 11.3 ± 7.9 d, P = 0.002) in the stapled anastomosis group than in the hand-sewn anastomosis group. There were no differences in the incidences of delayed gastric emptying and other postoperative complications between the groups. CONCLUSION These results suggest that stapled gastro/duodenojejunostomy shortens reconstruction time during PpPD without affecting the incidence of delayed gastric emptying.

A new oval multichannel port to facilitate reduced port distal gastrectomy.

Abstract Background: This report describes the techniques and outcomes of reduced port distal gastrectomy (RPDG) using a new oval multichannel port. Material and methods: We performed reduced port distal gastrectomy through the E·Z Access™ oval type device with three trocars in the umbilical incision, plus the use of additional 5 mm and 2 mm ports. All routine procedures performed in conventional laparoscopic distal gastrectomy (CLDG) were achieved in RPDG. Results: We employed this technique without the use of additional trocars or conversion to laparotomy in all 25 patients. The median length of the operation was 340 (range, 220–487) minutes, and the median estimated blood loss was 30 (range, 5–440) ml. Neither major postoperative complications, such as anastomotic leakage and stricture, nor postoperative mortality were observed. The mean length of the hospital stay was 11 days. The umbilical wound was indistinct. The patients were also highly satisfied with the cosmetic outcome. Conclusion: Reduced port surgery using the E·Z Access™ oval type device was successfully applied for gastric cancer. This method is technically feasible, produces superior cosmetic results and thus could be an attractive surgical option for gastric cancer patients.

Single-incision laparoscopic cholecystectomy for acute cholecystitis: A retrospective cohort study of 52 consecutive patients

BACKGROUND Single-incision laparoscopic cholecystectomy (SILC) has become increasingly popular but its role in acute cholecystitis remains controversial. METHODS We compared the clinical features and outcomes of SILC procedures between 52 patients with acute cholecystitis (the AC group) and 308 patients without acute cholecystitis (the NAC group). We also analyzed clinical variables to identify factors affecting difficulties associated with SILC for acute cholecystitis. RESULTS The patients in the AC group were significantly older than those in the NAC group (72 vs. 61 years, median, P = 0.0005). The preoperative levels of white blood cell counts were significantly higher in the AC group than in the NAC group (6600 vs. 5500/μL, P = 0.0004). The operative time was significantly longer in the AC group than in the NAC group (188 vs. 135 min, P < 0.0001). The volume of intraoperative blood loss was significantly larger in the AC group than in the NAC group (20 vs. 5 mL, P < 0.001). Furthermore, additional trocar insertion was required in 12% in the NAC group, whereas it was required in 60% in the AC group (P < 0.0001). Regarding the difficulties of SILC for acute cholecystitis, delayed operation (after 72 h from the onset) was significantly associated with a prolonged operative time, while a higher grade of acute cholecystitis (grade II or III) was significantly associated with an increased blood loss during surgery. CONCLUSIONS These findings suggest that when compared to SILC for gallbladder diseases without acute inflammation, SILC for acute cholecystitis was associated with a longer operative time, increased blood loss, higher rate of additional trocar requirement, higher rate of postoperative complications, and longer hospital stay. The difficulties associated with SILC for acute cholecystitis were affected by the timing of surgery and the grade of inflammation.

Association of hereditary spherocytosis with familial adenomatous polyposis in a pedigree: a new syndrome or coincidence?

No association of familial adenomatous polyposis (FAP) and hereditary spherocytosis (HS) has been reported, both of which are inherited in an autosomal dominant manner. We present the first reported case of FAP with spherocytosis and construct the family pedigree. In the patients pedigree, both FAP and spherocytosis were inherited in an autosomal dominant trait. In the 34-year-old Japanese probands leukocytes, we found no abnormal chromosomal band, and a germline mutation of the APC gene was not detected. All possible genes reported to be linked to HS were located far from chromosome 5q on which the APC gene is located. Although it is unknown if erythrocyte membrane disorder is an additional phenotype of FAP, to the best of our knowledge, this is the first documentation of FAP associated with spherocytosis.

The prognostic significance of the expression of monocarboxylate transporter 4 in patients with right- or left-sided colorectal cancer

Monocarboxylate transporter 4 (MCT4) is a proton pump that exchanges lactate through the plasma membrane. The present study investigated the clinical significance of the expression of MCT4 in patients with right‐ or left‐sided colorectal cancer (CRC).