Deprescribing Using the Guidelines for Medical Treatment and Its Safety in the Elderly and Changes in Patient QOL and Activities of Daily Living.

Pharmacists applied deprescribing, which is a process for the rational use of drugs, for 13 at-home patients. The standard used for the rational use of drugs was the "Guidelines for Medical Treatment and Its Safety in the Elderly" (the Guidelines). The results of the deprescribing were discussed with physicians to determine prescriptions. After the prescription change, activities of daily living (ADL) and QOL were assessed using the Barthel Index and SF-36v2, respectively. Potentially inappropriate medications (PIMs) were detected in 10 of the 13 patients (76.9%). This detection rate is higher than previous PIM detection rates of 48.4% and 40.4% reported in prescriptions for home-care patients in Japan under the Beers and STOPP/START criteria. The Guidelines appeared useful as a decision support tool for deprescribing. The patients continuing the changed prescriptions showed no decrease in ADL or QOL after deprescribing, suggesting its rationality. The 10 measurement items of the Barthel Index were all suitable for evaluating the physical conditions of the patients. Meanwhile, SF-36v2 includes many items, but few indexes were directly applicable.

Laparoscopic lysis for jejunostomy-related ileus following laparoscopy-assisted total gastrectomy: a case report.

A 54-year-old man was admitted to our hospital with severe nausea, vomiting and abdominal pain. He had had laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction and tube jejunostomy for gastric cancer 2 years earlier. Abdominal CT revealed that the duodenum and upper jejunum were markedly dilated and that the dilated jejunum had collapsed at the jejunostomy site. Emergency laparoscopic surgery with three ports was performed for jejunostomy-related ileus. Abdominal adhesion was very small, and the Roux-en-Y limb was rotated counterclockwise at the jejunostomy site. A magnified laparoscopic view showed that the site of peritoneopexy was the axis of rotation. After the axis was dissected with a Harmonic scalpel, the rotation was released immediately. The patient's postoperative course was uneventful and he was discharged 4 days after the operation. Because the axis of rotation was identified easily by laparoscope, laparoscopic surgery was a safe and useful technique for a patient with jejunostomy-related ileus.

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

BACKGROUND: Chemoradiation 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 METHODS: HLA-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 (60 Gy) with concurrent cisplatin (40 mg/m²) and 5-fluorouracil (400 mg/m²). Peptide vaccines mixed with incomplete Freund's adjuvant were injected subcutaneously once a week on at least 8 occasions combined with CRT. RESULTS: Vaccination 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 4.6 years. CONCLUSIONS: A 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 REGISTRATION: ClinicalTrial.gov, number NCT00632333.

Truncal vagotomy temporarily decreases the pro- and anti-inflammatory cytokine levels in the small intestine.

PURPOSE: The vagus nerve exerts immunomodulatory functions by inhibiting pro-inflammatory cytokine overproduction. Because vagotomy is a standard procedure during the radical operation for esophageal or gastric cancer, the postoperative clinical course might be related to vagotomy-associated changes in the cytokine milieu. We herein examined the gut cytokine kinetics after vagotomy in mice. METHODS: Thirty-eight male Institute of Cancer Research mice underwent sham or sub-diaphragmatic truncal vagotomy. The whole small intestine was harvested on postoperative day (POD) 14 (sham: vagotomy, n = 9:10) or 20 (n = 9:10). The pro- and anti-inflammatory cytokine levels in the plasma, jejunum, ileum and whole small intestine were evaluated. RESULTS: The plasma cytokine levels were similar in the vagotomy and sham groups on POD 14 and 20. However, both the pro- and anti-inflammatory cytokine levels tended to be lower on POD 14 and higher on POD 20 in the vagotomy group than in the sham group. With regard to the cytokine kinetics, the jejunal IL-12p70, TNF-α, MCP-1 and IL-10, ileal IL-12p70, TNF-α, IL-6, MCP-1 and IL-10, and whole small intestinal IL-12p70, TNF-α, IFN-γ, MCP-1 and IL-10 of the vagotomy group all significantly increased on POD 20 as compared to POD 14. CONCLUSION: Vagotomy has a major impact on the gut cytokine milieu. Vagotomy may initially inhibit both pro- and anti-inflammatory cytokine production, while both later increase.

The breath test system involving a novel tracer, ¹³C-uracil and Wagner-Nelson analysis: comparison with the gastric emptying scintigraphy.

BACKGROUND/AIMS: In this pilot study, a new breath test system for gastric emptying study has been proposed. METHODOLOGY: The system involves 13C-uracil as a novel tracer and the Wagner-Nelson method for analyzing breath data. RESULTS: In three healthy volunteers, the new breath system allowed quantification of gastric emptying profiles as accurately as the scintigraphic technique. CONCLUSIONS: Further validation studies with a lager sample size are needed.

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.

Chronic pain and discomfort after inguinal hernia repair.

PURPOSE: The purpose of this study was to estimate the incidence and degree of persistent chronic pain after inguinal hernia repair performed in our hospitals. METHODS: We 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 3 months previously. RESULTS: There 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. CONCLUSIONS: The 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.

Papillary muscle head approximation for the treatment of mitral valve regurgitation combined with aortic valve disease.

We initiated an original papillary muscle head approximation procedure, commonly known as Sandwich plasty, for the treatment of ischemic mitral regurgitation (MR). In this study, we evaluated the appropriateness of this procedure for functional MR associated with aortic valve disease. Fifteen patients who had undergone Sandwich plasty combined with aortic valve surgery were included in this study. The mean age of the patients was 69 years. Predominant aortic valve diseases were regurgitation in 8 patients and stenosis in 7 patients. Aortic valve replacement was performed in 14 patients and David surgery in one. The mitral valve was approached through the aortic annulus in 9 patients (the transaortic group). Six other patients with mitral valve annulus of 30 mm or larger underwent concomitant mitral ring-annuloplasty through a left atrial incision (the LA group). The tenting height of the mitral valve and left ventricle diastolic diameter significantly decreased after surgery in both groups. After surgery, residual moderate or mild MR was detected in two patients in the transaortic group. In the LA group, residual mitral regurgitation was not detected. In the follow-up study, prominent MR occurred in two patients in the transaortic group. The MR free rate two years after surgery was 83% in the total patient population. Sandwich plasty was simple and effective in the treatment of functional mitral regurgitation combined with aortic valve surgery. A transaortic approach is effective in obviating a separate left atriotomy and reducing operation time.