Tsuyoshi Inaba

Clinicopathological and prognostic significance of microRNA-107 and its relationship to DICER1 mRNA expression in gastric cancer.

microRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression. It is known that miRNA-107 (miR-107) promotes cancer invasion and metastasis. However, the relationship between clinicopathological factors and the prognostic significance of miR-107 for gastric cancer patients remains elusive. In this study, we evaluated the prognostic value of miR-107 using tissue samples from gastric cancer patients. Furthermore, the relationship between miR-107 and the mRNA levels of its target gene DICER1 was examined. The expression levels of miR-107 and DICER1 mRNA in tumor tissues and adjacent normal tissues of 161 gastric cancer patients were examined (TNM stage I, 29 patients; stage II, 31 patients; stage III, 51 patients and stage IV, 50 patients). miR-107 levels were measured by Taqman microRNA assays, and DICER1 mRNA levels were measured by the Taqman real-time RT-PCR method. In the analysis by real-time PCR-based miRNA arrays using pooled RNA samples from five gastric cancer patients, expression of miR-107, miR-21, miR-196a, miR-26b, miR-9, miR-142-3p, miR-30b, miR-150, miR-191 and miR-17 was found to be upregulation. The mean expression level of miR-107 was significantly higher in the tumor tissues compared to that of normal tissues. In the comparison of clinicopathological factors, miR-107 expression showed significant association with depth of tumor invasion, lymph node metastasis and stage. In Kaplan-Meier survival curve analysis, overall survival rates (OS) and disease-free survival rates (DFS) of patients with high miR-107 expression were significantly worse than those of patients with low miR-107 expression. In the Cox multivariate analysis, it was shown that miR-107 expression in gastric cancer tissues was an independent prognostic factor for OS and DFS. Significant inverse correlations were demonstrated between miR-107 and DICER1 mRNA. Our results indicate that miR-107 may be useful as an effective biomarker for prediction of a poor prognosis in gastric cancer patients.

Prospective randomized study of two laparotomy incisions for gastrectomy: midline incision versus transverse incision

BackgroundWe performed a randomized study to evaluate the differences between upper midline incision and transverse incision for gastrectomy.MethodsPatients undergoing distal gastrectomy or total gastrectomy for gastric cancer were randomly allocated to have either an upper midline incision or a transverse incision. The times taken to open and close the abdominal cavity, the number of doses of postoperative analgesics, and the incidence of postoperative pneumonia, wound infection, and intestinal obstruction were compared between the patients having the two incisions.ResultsTimes for both opening and closing the abdominal cavity were longer with a transverse incision, in both the distal gastrectomy group and total gastrectomy group. In the patients in whom continuous epidural analgesia was used postoperatively, the number of additional doses of analgesics was smaller in the transverse-incision group after distal gastrectomy. The incidence of postoperative pneumonia was lower in the transverse-incision group after distal gastrectomy. The number of patients with postoperative intestinal obstruction was smaller in the transverse-incision group than in the midline-incision group after distal gastrectomy. In contrast to distal gastrectomy, there was no significant difference in the number of doses of postoperative analgesics, incidence of postoperative pneumonia, or incidence of postoperative intestinal obstruction between the two study groups after total gastrectomy.ConclusionA transverse incision for distal gastrectomy may be more beneficial than an upper midline incision in attenuating postoperative wound pain, decreasing the incidence of postoperative pneumonia, and preventing postoperative intestinal obstruction.

Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients.

BackgroundChemoradiation therapy (CRT) has been widely used for unresectable esophageal squamous cell carcinoma (ESCC) patients. However, many patients develop local recurrence after CRT. In this study, we hypothesized that the immunotherapy by peptide vaccine may be effective for the eradication of minimal residual cancer cells after CRT. This study was conducted as a phase I clinical trial of multiple-peptide vaccine therapy combined with CRT on patients with unresectable ESCC.Patients and methodsHLA-A*2402 positive 11 unresectable chemo-naïve ESCC patients were treated by HLA-A*2402-restricted multi-peptide vaccine combined with CRT. The peptide vaccine included the 5 peptides as follows; TTK protein kinase (TTK), up-regulated lung cancer 10 (URLC10), insulin-like growth factor–II mRNA binding protein 3 (KOC1), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). CRT consisted of radiotherapy (60xa0Gy) with concurrent cisplatin (40xa0mg/m2) and 5-fluorouracil (400xa0mg/m2). Peptide vaccines mixed with incomplete Freund’s adjuvant were injected subcutaneously once a week on at least 8 occasions combined with CRT.ResultsVaccination with CRT therapy was well-tolerated, and no severe adverse effects were observed. In the case of grade 3 toxicities, leucopenia, neutropenia, anemia and thrombocutopenia occurred in 54.5%, 27.3%, 27.3% and 9.1% of patients, respectively. Grade 1 local skin reactions in the injection sites of vaccination were observed in 81.8% of patients. The expressions of HLA class I, URLC10, TTK, KOC1, VEGFR1 and VEGFR2 antigens were observed in the tumor tissues of all patients. All patients showed peptide-specific cytotoxic T lymphocytes responses in at least one of the 5 kinds of peptide antigens during the vaccination. Six cases of complete response (CR) and 5 cases of progressive disease (PD) were observed after the 8th vaccination. The 4 CR patients who continued the peptide vaccination experienced long consistent CR for 2.0, 2.9 4.5 and 4.6xa0years.ConclusionsA combination therapy of multi-peptide vaccine with CRT can successfully be performed with satisfactory levels of safety, and application of this combination therapy may be an effective treatment for patients with unresectable ESCC.Trial registrationClinicalTrial.gov, number NCT00632333.

Chronic pain and discomfort after inguinal hernia repair.

PurposeThe purpose of this study was to estimate the incidence and degree of persistent chronic pain after inguinal hernia repair performed in our hospitals.MethodsWe mailed a questionnaire on the frequency and intensity of postoperative inguinal pain and discomfort to 219 adult patients who had undergone inguinal hernia repair in one of our hospitals more than 3xa0months previously.ResultsThere were 191 (87.2%) respondents, 28 (14.7%) of whom reported pain and 33 (17.3%) reported discomfort. The frequency of pain was “rare” in more than half of the patients who reported pain. No patient reported “continuous” pain. The intensity of the pain was “mild” in most of the patients, and none reported “pain that required a painkiller”. The answers on the face scale questionnaire (score “0” to “10”) were “0” or “1” for most of the patients. The incidence of chronic pain and/or discomfort was significantly higher in women than in men, and tended to be higher in patients who had undergone repair using onlay mesh.ConclusionsThe frequency and intensity of persistent chronic pain or discomfort after inguinal hernia repair was not high or severe. These data will be useful for further studies to determine the best treatment for adult inguinal hernia.

Surgical management of adult sigmoid colon intussusception caused by a malignant tumor: report of a case.

A 67-year-old man was admitted for investigation of bloody stools. The sigmoid colon was found to be intussuscepted into the rectum very close to the anus, making reduction difficult. After dividing the peritoneum, the surgeon inserted his hands below the peritoneal reflection along the rectum and pushed the intussusceptum back from the distal to the proximal rectum using a milking action. The rectum was divided 5u2009cm from the peritoneal reflection, and the sigmoid colon was divided 10u2009cm proximally from the intussusception. The proximal end of the sigmoid colon was brought out as a colostomy. The residual rectum and the descending colon were anastomosed 5 months after the first operation. We present a case of adult intussusception of the sigmoid colon caused by a well-differentiated adenocarcinoma, which was successfully treated by manually reducing the intussusception, whereby abdominoperineal resection was avoided.

Recurrent Laryngeal Nerve Monitoring during Thoracoscopic Esophagectomy

IntroductionThere have been several reports on the feasibility and curability of thoracoscopic esophagectomy, which may reduce injury to the thoracic cage and decrease the invasiveness of surgery. Although the recurrent laryngeal nerve (RLN) is identified and kept intact during operations, RLN palsy sometimes occurs. Currently, surgical aides, including intraoperative neurological monitoring, are being utilized to avoid RLN injury during thyroid surgery. This system is utilized during thoracoscopic esophagectomy in the prone position.Patients and methodsSeven consecutive patients (six men, one woman; age range 62–74xa0years; mean 68xa0years) were included. Patients underwent general anesthesia and were intubated using the NIM TriVantage™ electromyography (EMG) tube. One-lung ventilation was performed with an endobronchial blocker. Thoracoscopic esophagectomy was performed in the prone position. The nerve stimulator was calibrated to 0.5xa0mA, and after the RLN was visually identified it was subsequently stimulated, which also confirmed normal machine functioning. In some situations, in the absence of a response, stimuli were increased to 1.0xa0mA and then 2.0xa0mA.ResultsIntraoperatively, all seven patients had their nerve signals monitored. In one case, a nerve signal disappeared after complete lymph node dissection along the left RLN. This system could identify the site of injury, and the thoracoscopic magnified view allowed the disrupted point to be located precisely. When we checked VTR after surgery, the source of injury was one point tension of the nerve pulled by fiber during lymph node dissection.ConclusionsIntraoperative RLN monitoring during thoracoscopic esophagectomy in the prone position, with one-lung ventilation performed using the TriVantage™ EMG tube and a bronchial blocker, is technically feasible, easy, and reliable.

A randomized clinical study on postoperative pain comparing the Polysoft patch to the modified Kugel patch for transinguinal preperitoneal inguinal hernia repair

PurposeThe transinguinal preperitoneal approach is a relatively new technique for inguinal hernia repair. Two types of memory-ring mesh are available in Japan: the modified Kugel patch (MK) and the Polysoft patch (PP). We tested the hypothesis that the PP is noninferior to the MK with respect to chronic postoperative pain.MethodsAn unblinded randomized controlled trial was conducted to assess the noninferiority of PP compared to MK with a 5xa0% noninferiority margin. A total of 442 inguinal hernia patients operated on from November 2010 to December 2012 were included in this study. The primary endpoint was the pain score assessed by the visual analog scale (VAS) (0–1 vs. 2–10) 1xa0year after surgery.ResultsThe patients were randomized to the PP and MK groups (nxa0=xa0221 each). One year after surgery, 206 patients (95.4xa0%) in the PP group and 182 patients (89.6xa0%) in the MK group rated pain at 0–1 on the VAS scale. According to this rating, the PP group appeared not to be inferior to the MK group (95xa0% confidence interval, 0.7–10.7xa0%, Pxa0<xa00.05). Furthermore, crude superiority tests, adjusting for 1xa0month of pain, denoted that the outcomes were significantly improved with the PP compared to the MK.ConclusionsThe use of the PP was noninferior to the MK with respect to the severity of postoperative chronic pain scores 12xa0months after surgery.

Segmental Intestinal Preservation and Enteral Nutrition Help to Maintain the Intestinal Function After a Massive Intestinal Resection: Report of a Case

Abstract We report a case in which both segmental intestinal preservation and enteral nutrition helped to maintain the intestinal function after a massive bowel resection for superior mesenteric artery (SMA) thrombosis. A 53-year-old Japanese man was admitted to our hospital with acute abdomen. Extensive necrosis of the small intestine was found during the operation; however, a loop of the ileum appeared to be viable. A massive resection of the small intestine which preserved a 50-cm length of the viable ileum loop was thus performed. However, diffuse stenosis of the remaining ileum was found after surgery. An end-to-end anastomosis of the distal end of the preserved ileum loop and the terminal ileum was made in the second operation, and enteral nutrition was infused to improve the remnant intestinal function. A jejunoileostomy was performed in the final operation. An X-ray study after the final operation showed the stenosis of the remaining ileum to have improved. The patient therefore did not need any nutritional support after being discharged.

Two cases of early recurrence after transabdominal preperitoneal inguinal hernia repair

We performed transabdominal preperitoneal inguinal hernia repair in 46 patients (58 diseases), two of whom experienced early recurrence after mesh repair. Case 1 was a 76‐year‐old man with a bilateral inguinal hernia (recurrence site, left indirect hernia) after appendectomy. The recurrence occurred 1 month after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using the direct Kugel® patch with an anterior technique. Case 2 was a 79‐year‐old man with a bilateral inguinal hernia (recurrence site, right direct hernia with an orifice >3 cm) after appendectomy. The recurrence occurred 3 months after transabdominal preperitoneal inguinal hernia repair. The mesh was dislocated to the lateral side, and we repaired it using an ULTRAPRO® Plug with an anterior technique under laparoscopic observation. We believe the recurrences resulted from insufficient internal exfoliation and fixation affected by complicated exfoliation of the preperitoneal space with omental adhesion after intraperitoneal surgery.

Seven esophageal perforation cases after aortic replacement/stenting for thoracic aortic dissection or aneurysm

BackgroundEsophageal perforation after aortic replacement/stenting for aortic dissection or aneurysm is a rare but severe complication. However, its cause, standard treatment, and prognosis are unclear. We analyzed the treatment and outcome retrospectively from seven cases experienced at our hospital.Case presentationThe median age of the patients was 70xa0years (range, 41–86), and six of the seven cases were male. As the first treatment, aortic replacement techniques were performed in five, and thoracic endovascular aortic repair (TEVAR) procedure was performed in two. We evaluated the treatment of the perforation, the cause of death, and the median survival time after reparative surgery (esophagectomy).Initial treatment of the perforation was esophagectomy without reconstruction in six and esophagogastric bypass (later, esophagectomy was performed) in one. Three of seven cases could be discharged from hospital or moved to another hospital, but two of these three cases died of major bleeding on postoperative days 320 and 645. The other four esophagectomy cases died in hospital because of sepsis on postoperative days 14, 30, and 41 and major bleeding on postoperative day 54. The one surviving case was a 65-year-old man who underwent reconstruction, and was still alive without signs of infection at 424xa0days postoperatively.ConclusionThe prognosis of esophageal perforation cases after aortic replacement/stenting for thoracic aortic dissection or aneurysm is poor, though there were some cases with relatively long survival. Therefore, the indication for invasive esophagectomy should be decided carefully. Control of infection including regional infection is essential for successful treatment.