Mitsuo Nishiyama

Low invasiveness of thoracoscopic esophagectomy in the prone position for esophageal cancer: a propensity score-matched comparison of operative approaches between thoracoscopic and open esophagectomy

BackgroundIn this study, cytokine levels, outcome, and survival rates after esophagectomy for esophageal cancer were retrospectively investigated in a propensity score-matched comparison of operative approaches between the thoracoscopic esophagectomy (TE) in the prone position and open esophagectomy (OE).Patients and MethodsBetween 2005 and 2014, TE was performed on a group of 85 patients, which was compared with a group of 104 OE cases. Eventually, 65 paired cases were matched using propensity score matching.ResultsAlthough the TE group underwent a significantly longer operation time than the OE group (P < 0.001), the TE group exhibited less blood loss (P < 0.001) and had a shorter postoperative hospital stay (P = 0.038) than the OE group. The serum interleukin-6 levels on ICU admission (P < 0.001) and on POD 1 (P < 0.001) were significantly lower in the TE group. The interleukin-10 levels on ICU admission (P < 0.001), POD 1 (P = 0.016), and POD 3 (P < 0.001) were also significantly lower in the TE group. Pulmonary complication was significantly lower in the TE group (P = 0.043). The 5-year PFS rates in the TE and OE groups were 70.6 and 58.7% (P = 0.328), respectively, and OS rates were 64.9 and 50.2% (P = 0.101), respectively.ConclusionTE compared to OE is a less invasive procedure with lower surgical stress and less pulmonary complication for the treatment of esophageal squamous cell carcinoma.

Metastatic ability and the epithelial‐mesenchymal transition in induced cancer stem‐like hepatoma cells

Cancer stem cells (CSCs) are thought to play important roles in cancer malignancy. Previously, we successfully induced sphere cancer stem‐like cells (CSLCs) from several cell lines and observed the property of chemoresistance. In the present study, we examined the metastatic potential of these induced CSLCs. Sphere cancer stem‐like cells were induced from a human hepatoma cell line (SK‐HEP‐1) in a unique medium containing neural survival factor‐1. Splenic injection of cells into immune‐deficient mice was used to assess hematogenous liver metastasis. Transcriptomic strand‐specific RNA‐sequencing analysis, quantitative real‐time PCR, and flow cytometry were carried out to examine the expression of epithelial‐mesenchymal transition (EMT)‐related genes. Splenic injection of CSLCs resulted in a significantly increased frequency of liver metastasis compared to parental cancer cells (P < .05). In CSLCs, a mesenchymal marker, Vimentin, and EMT‐promoting transcription factors, Snail and Twist1, were upregulated compared to parental cells. Correspondingly, significant enrichment of the molecular signature of the EMT in CSLCs relative to parental cancer cells was shown (q < 0.01) by RNA‐sequencing analysis. This analysis also revealed differential expression of CD44 isoforms between CSLCs and parental cancer cells. Increasing CD44 isoforms containing an extra exon were observed, and the standard CD44 isoform decreased in CSLCs compared to parental cells. Interestingly, another CD44 variant isoform encoding a short cytoplasmic tail was also upregulated in CSLCs (11.7‐fold). Our induced CSLCs possess an increased liver metastatic potential in which promotion of the EMT and upregulation of CD44 variant isoforms, especially short‐tail, were observed.

Efficacy of Perioperative Immunonutrition in Esophageal Cancer Patients Undergoing Esophagectomy

OBJECTIVE Malnutrition is common in patients with esophageal cancer, resulting in increased postoperative complications and mortality. Although preoperative immunonutrition can significantly reduce the incidence of postoperative infectious complications, its effect in patietns with esophageal cancer undergoing esophagectomy remains unclear. The aim of this study was to investigate the effects of perioperative immunonutritional support on the postoperative course and long-term survival of this group of patients. METHODS This prospective, randomized study enrolled 40 patients with thoracic esophageal carcinoma undergoing esophagectomy. The patients were divided into two groups and received either immunomodulating enteral nutrition (IMPACT group; IG) or standard enteral nutrition (Ensure group; EG) continuously for 7 d before and 7 d after surgery. Nutritional status, such as rapid turnover protein, postoperative intensive care unit (ICU) length of stay (LOS), postoperative hospital LOS, morbidity, and mortality were investigated prospectively. RESULTS There were no significant differences in patient demographic characteristics between the two groups. Levels of retinol-binding protein, as a rapid-turnover protein, were significantly higher on postoperative day (POD) -1, 7, and 14 in the IG compared with the EG group (P = 0.009, P = 0.004, and P = 0.024, respectively). The incidence of postoperative infectious complications and changes to therapeutic antibiotics were significantly lower in the IG group than in the EG group (P = 0.048 and P = 0.012, respectively). There was no significant difference in postoperative ICU or postoperative hospital LOS between the two groups. The 5-y progression-free survival rates in the IG and EG groups were 75% and 64%, respectively (P = 0.188), and the overall survival rates were 68% and 55%, respectively (P = 0.187). CONCLUSIONS Perioperative immunonutrition may improve early postoperative nutritional status and reduce postoperative infectious complications in patients with esophageal cancer undergoing esophagectomy.

Association of tumor necrosis factor‑α polymorphism with chemotherapy‑induced oral mucositis in patients with esophageal cancer

The purpose of this study was to evaluate the association between tumor necrosis factor (TNF)-α polymorphisms and oral mucositis (OM) from 5-fluorouracil (5-FU) plus cisplatin (CDDP) chemotherapy for esophageal cancer. The rs1799964 polymorphism of TNF-α was genotyped using the tetra-primer amplification refractory mutation system polymerase chain reaction. The experimental group comprised 64 patients who received chemotherapy for esophageal cancer between 1997 and 2004; a total of 106 patients between 2005 and 2013 were investigated as the validation group. Univariate analysis of the experimental group revealed that the TT genotype of TNF-α rs1799964 was significantly higher in patients with grade 1-4 OM compared with the TC/CC genotypes [univariate odds ratio (OR)=4.0; P=0.029]. Similarly, univariate analysis of the validation group revealed that the percentage of the TT genotype was significantly higher in patients with grade 1-4 OM compared with the TC/CC genotypes (OR=2.8; P=0.043). This difference in risk was replicated in the validation cohort. Thus, the TT genotype of TNF-α rs1799964 may be a predictor of chemotherapy-induced OM in patients with esophageal cancer.

Internal Hernia Resulting in Bowel Obstruction After Laparoscopic Colectomy

A 65-year-old woman underwent laparoscopic-assisted sigmoidectomy for management of sigmoid colon cancer. Her postoperative recovery was initially uneventful; however, on postoperative day 12, the patient suddenly complained of abdominal pain. Further surgical intervention was finally performed on postoperative day 21 because conservative treatment had been unsuccessful in relieving the obstruction. Laparoscopic surgery revealed that a segment of the proximal jejunum had herniated through an orifice, forming an adhesion between the mesentery of the ileum and the incised retroperitoneum of the mesenteric opening. The obstruction was relieved by laparoscopic adhesiolysis. Only 7 cases have previously been reported where the mesenteric opening has caused an internal hernia resulting in bowel obstruction. This case may suggest the need for closure of the mesenteric opening to prevent this complication after laparoscopic colectomy; however, there is no consensus on whether a mesenteric opening should be closed. Further research is needed to identify the patients who would benefit from the closure of mesenteric defects during laparoscopic-assisted colectomy.