High prevalence of vitamin D deficiency in patients with xeroderma pigmetosum-A under strict sun protection.

BACKGROUND/OBJECTIVES: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by defective repair of ultraviolet (UV) irradiation-induced DNA damage and high risk of skin cancer. Thus, these patients require strict photoprotection. Considering the importance of UV-mediated cutaneous vitamin D production, such rigorous photoprotection would cause vitamin D deficiency. Then, we have studied the vitamin D status in patients with XP-A, a group requiring the most strict photoprotection. SUBJECTS/METHODS: Twenty-one patients with XP-A (aged 6-25) were evaluated for their vitamin D intake, serum levels of 25-hydroxy-vitamin D (25OHD) and parathyroid hormone (PTH). Vitamin D intake was assessed by a 2-day food weighing method. RESULTS: Median dietary intake of vitamin D was 4.1 µg/day, and the median concentrations of serum 25OHD and PTH were 7.7 and 49.9 pg/ml, respectively. In 76% of the patients, serum 25OHD level was lower than 10 ng/ml, indicating vitamin D deficiency. Vitamin D intake and serum 25OHD level were significantly lower in patients under enteral nutrition (EN) than those with oral intake (OI). Multivariate analyses revealed that EN was a significant predictor of decreased serum 25OHD level (ß coefficient=-0.59, P=0.03). CONCLUSIONS: Vitamin D deficiency is highly prevalent in XP-A patients, and supplementation should be considered to avoid unfavorable skeletal consequences in these patients. In addition, determination of dietary vitamin D requirement has been a difficult work issue in the decision of dietary reference intakes (DRIs) because of its cutaneous production. Data from XP patients would yield useful information for the determination of DRIs for vitamin D.

Factors associated with the presence of multiple Lugol-voiding lesions in patients with esophageal squamous-cell carcinoma.

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol-voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence-specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84-122.45: P = 0.011), presence of the ALDH2-2 allele (OR 4.5, 95% CI 1.55-13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02-6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13-88.44: P = 0.038) and presence of the ALDH2-2 allele (OR 4.56, 95% CI 1.4-14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2-2 allele (OR 17.5, 95% CI 1.97-155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2-2 allele (OR 8.85, 95% CI 1.68-46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2-2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2-2 allele (OR 4.0, 95% CI 0.54-29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2-2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.

New flexible endoscopic full-thickness suturing device: a triple-arm-bar suturing system.

BACKGROUND AND STUDY AIM: A reliable full-thickness suturing device is necessary for pure natural orifice transluminal endoscopic surgery (NOTES). The present study focused on assessing the reliability of a new suturing device. METHODS: A total of 60 single sutures were tested to close 5-cm incisions in 8-cm square pieces of resected swine stomach. Each incision was sutured by an over-the-scope clip (OTSC; n = 20), a single hand-sewn stitch (n = 20), or a single triple-arm-bar suturing system (TBSS) stitch. The maximum pulling force durability (MPD) of each suture was tested. To assess the reliability of the TBSS for endoscopic full-thickness resection (EFTR), 60 EFTRs of 50 mm diameter were performed on excised swine stomachs. After EFTR, full-thickness sutures were made using 3-stitch OTSCs (n = 20), 10-stitch hand-sewn sutures (n = 20), or 10-stitch TBSS sutures (n = 20). Outcomes were the MPD test for both single stitch and multiple stitch applications and the suturing time for single-stitch sutures. RESULTS: In the single-stitch MPD tests, there were significant differences between OTSCs and hand-sewn sutures (P = 0.0002) and between OTSCs and TBSS sutures (P = 0.0001), but no significant difference between hand-sewn and TBSS sutures. The multiple-stitch sutures revealed significant differences between OTSCs and hand-sewn sutures (P = 0.0039), and between OTSCs and TBSS sutures (P = 0.013). There was no significant difference between hand-sewn and TBSS sutures. There were significant differences in suture times between OTSC, hand-sewn sutures, and TBSS sutures (P < 0.05). CONCLUSIONS: Both single-stitch and multiple-stitch sutures using TBSS have similar strength to hand-sewn sutures. TBSS is a reliable suturing device.

Successful treatment of duodenal carcinoid tumor by laparoscopy-assisted endoscopic full-thickness resection with lymphadenectomy.

Reports on endoscopic full-thickness resection of the duodenum using the endoscopic submucosal dissection technique are rare. Here we present a case of a duodenal bulb carcinoid tumor successfully treated by laparoscopy-assisted endoscopic full-thickness resection (LAEFR). An asymptomatic 65-year-old woman had a 10-mm, submucosal tumor on the anterior wall of the duodenal bulb. Abdominal CT revealed an enlarged lymph node adjacent to the duodenum and pancreas. Although we informed the patient of the need for pancreatoduodenectomy with a lymphadenectomy, the patient expressly requested LAEFR. After negative nodal metastasis was confirmed by an intraoperative frozen section of the enlarged nodes, LAEFR was performed using the endoscopic submucosal dissection technique under the laparoscopic assistance. The duodenal wall defect was closed by laparoscopy with an Albert anastomosis. The entire circumferential margin of the specimen was histopathologically negative for carcinoid tumor cells. In summary, LAEFR enables en bloc and whole-layer excision of nonperiampullary duodenal lesions with a sufficient surgical margin, both vertically and laterally. LAEFR is a minimally invasive and effective treatment for selected patients with duodenal carcinoid tumor.

Local steroid injection into the artificial ulcer created by endoscopic submucosal dissection for gastric cancer: prevention of gastric deformity.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) of large gastric lesions results in an extensive artificial ulcer that can lead to marked gastric deformity. The aim of the current study was to evaluate therapeutic efficacy in the prevention of gastric deformity of local triamcinolone acetonide (TCA) injection into the extensive artificial ulcer following ESD. PATIENTS AND METHODS: A total of 45 patients who were diagnosed with early gastric cancer were enrolled. Patients were randomly assigned by the sealed-envelope randomization method to either local TCA injections (n = 21) or sham-control (n = 20) groups. Two clips were placed at the two maximum outer edges of the artificial ulcer after the lesion had been resected (Day 0). Local TCA injections were performed on postoperative Day 5 and Day 12. The distance between the two clips was measured by endoscopic measuring forceps on Days 5, 12, 30, and 60. Granulation formation and gastric deformity were evaluated by visual analog scale (VAS) on Days 30 and 60. RESULTS: Local TCA injection did not alter clip-to-clip distance on postoperative Day 60, and formation of flat granulation tissue over the ulcer was followed by regenerative mucosa without any gastric deformity. The sham-control group showed significant shortening of clip-to-clip distance compared with the local steroid-injected group and protruded forms of granulation tissue with mucosal convergence. Histological evaluation revealed prominent growth of neovessels, swelling, and marked increases in endothelial cells in the local steroid-injected group compared with the sham-control group. CONCLUSIONS: Local steroid injection into the floor of a post-ESD artificial ulcer promotes the formation of granulation tissue at an early stage of the healing process leading to regeneration of gastric mucosa without mucosal convergence or gastric deformity.

Monocyte chemoattractant protein-1 is associated with silent cerebral infarction in patients on haemodialysis.

BACKGROUND: In patients with chronic renal failure undergoing haemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of monocyte chemoattractant protein-1 (MCP-1) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased MCP-1 concentration correlate with the occurrence of SCI in HD patients. METHODS: Using cranial magnetic resonance imaging (MRI) findings, 52 Japanese patients undergoing HD were divided into two groups: with SCI (61 ± 7 years, mean ± SD, n= 28) and without SCI (60 ± 6 years, n= 24). The gender, metabolic profiles and MCP-1 concentration were compared between the two groups. RESULTS: The level of MCP-1 was higher in the with-SCI group than in the without-SCI group (P < 0.0001). The proportion of smokers was higher in the with-SCI group (P < 0.05) than in the without-SCI group. Plasma level of high-density lipoprotein cholesterol was lower, while uric acid level was higher, in the with-SCI group (P < 0.05 and P < 0.05 respectively) compared to the without-SCI group. Multiple logistic regression analysis identified MCP-1 level as being significantly associated with the presence of SCI (odds ratio 1.48, 95% confidence interval = 1.10-5.75, P < 0.0001). CONCLUSIONS: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI, and that MCP-1 is significantly associated with the presence of SCI in HD patients.

Establishment of pure NOTES procedure using a conventional flexible endoscope: review of six cases of gastric gastrointestinal stromal tumors.

An increasing number of reports have recently been published on hybrid natural orifice transluminal endoscopic surgery (NOTES). These reports do not address how to complete an operation with a flexible endoscope alone (pure NOTES), but rather how to combine use of an endoscope and a laparoscope. Surgical procedures using flexible and rigid endoscopes have been developed using different processes and concepts. Recognizing this conceptual difference, we conducted a study to address how to establish a pure NOTES procedure. Six patients with gastric gastrointestinal stromal tumors (GISTs) underwent hybrid NOTES. Each case was retrospectively reviewed to determine the appropriateness of the treatment and the usefulness of the endoscopic submucosal dissection (ESD) method, double-scope method, spaced perforation method, duodenal balloon occlusion method, and loop clip technique. The development of operative procedures that take advantage of the characteristics of flexible endoscopes, even with conventional flexible endoscopic devices and conventional endoscopes alone, may contribute to the realization of pure NOTES.

Narrow band imaging for detecting superficial squamous cell carcinoma of the head and neck in patients with esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Narrow band imaging combined with magnifying endoscopy (NBI-ME) is useful for the detection of superficial squamous cell carcinoma (SCC) within the oropharynx, hypopharynx, and oral cavity. The risk of a second primary SCC of the head and neck is very high in patients with esophageal SCC. This prospective study evaluated the detection rate of superficial SCC within the head and neck region (superficial SCCHN) with NBI-ME in patients with esophageal SCC. PATIENTS AND METHODS: Between March 2006 and February 2008, 112 patients with a current or previous diagnosis of esophageal SCC were enrolled. All patients underwent endoscopic screening of the head and neck by NBI-ME. The primary end point was the detection rate for superficial SCCHN. Secondary end points were to compare demographic characteristics between patients with and without superficial SCCHN and to assess the clinical course of patients with superficial SCCHN. RESULTS: The detection rate for superficial SCCHN was 13 % (15/112). The prevalence of multiple Lugol-voiding lesions, observed endoscopically throughout the esophageal mucosa after application of Lugol dye solution, was significantly higher in patients with superficial SCCHN than in those without (100 % vs. 24 %, P < 0.0001). Minimally invasive curative treatment with organ preservation was feasible without severe complications in patients with superficial SCCHN after curative treatment of esophageal SCC. CONCLUSIONS: In patients with esophageal SCC, NBI-ME is useful for detecting superficial SCCHN, thereby facilitating minimally invasive treatment.

Smoking is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients.

BACKGROUND: Smoking and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This study tested the hypothesis that smoking is associated with insulin resistance/hyperinsulinaemia and cardiovascular autonomic dysfunction in type 2 diabetic patients who are not treated with insulin. MATERIALS AND METHODS: The study patients were 22 current smokers with type 2 diabetes mellitus (age: 57 +/- 5 years, mean +/- SD) and 30 age-matched never-smoked patients with type 2 diabetes mellitus (control group, 57 +/- 8 years). The quality of blood glucose was assessed by fasting plasma glucose (FPG), fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index and haemoglobin A1c (HbA1c). The severity of smoking status was expressed by the Brinkman index, which is calculated as number of cigarettes per day multiplied by years of smoking. Cardiovascular autonomic function was assessed by baroreflex sensitivity (BRS), heart-rate variability, plasma norepinephrine concentration and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the current smokers group than in the never-smoked group (P < 0.05). Early and delayed (123)I-MIBG myocardial uptake values were lower (P < 0.05, and P < 0.01, respectively) and the percentage washout-rate of (123)I-MIBG was higher (P < 0.0001) in the current smokers group than in the never-smoked group. Fasting immunoreactive insulin (F-IRI) concentration (P < 0.0001) and the homeostasis model assessment (HOMA) index (P < 0.0001) were higher in the current smokers group than the never-smoked group. Multiple logistic regression analysis revealed that smoking was independently predicted by F-IRI and the percentage washout-rate of (123)I-MIBG. CONCLUSIONS: The results of the study suggested that smoking was associated with cardiovascular autonomic dysfunction and hyperinsulinaemia and that F-IRI and the percentage washout-rate of (123)I-MIBG were independent predictors of smoking in these Japanese patients with type 2 diabetes mellitus.

Efficacy of local dipyridamole therapy in a porcine model of arteriovenous graft stenosis.

Perivascular delivery of antiproliferative drugs has been proposed as an approach to prevent neointimal hyperplasia associated with hemodialysis polytetrafluoroethylene (PTFE) grafts. We examined this approach to deliver dipyridamole in a porcine graft model. PTFE grafts were implanted between the carotid artery and external jugular vein bilaterally in pigs. During the surgery or 1 week post-graft placement, dipyridamole (0.26-52 mg) alone or incorporated in microspheres was mixed with an injectable polymeric gel and applied to the graft-arterial and graft-venous anastomoses on one side, whereas the contralateral control graft received no treatment. Three or four weeks after operation, the grafts and adjacent vessels were explanted en bloc and cross-sections of the anastomoses were examined histologically. The degree of neointimal hyperplasia was quantified by planimetry. In separate experiments, dipyridamole was extracted from the explanted tissues and assayed by spectrofluorometry. The normalized median hyperplasia areas of the treated and control graft-venous anastomoses were 0.45 (25th-75th percentile, 0.30-0.86) and 0.24 (0.21-0.30), respectively (N=7; P=0.08). The median hyperplasia areas of the treated and control graft-arterial anastomoses were 0.12 (0.07-0.39) and 0.11 (0.09-0.13), respectively (N=7; P=0.31). The dipyridamole levels in the vascular walls around the anastomoses were at or above the in vitro inhibitory concentrations for approximately 3 weeks. These results suggest that the local perivascular sustained delivery of dipyridamole, even at high dosages, was ineffective in inhibiting neointimal hyperplasia associated with PTFE grafts in a porcine model.