DNA vaccine expressing HIV-1 gp120/immunoglobulin fusion protein enhances cellular immunity

In this study, we explored the possibility of augmenting human immunodeficiency virus (HIV) gp120-specific cell-mediated immune responses in mice by means of a DNA vaccine encoding a mouse Ig Fcγ2a fragment fused with gp120 (gp120-Ig, Ig-gp120). Western blotting analysis revealed that the HIV gp120 protein expression efficiency was higher in cells transfected with the gp120-Ig-coding plasmid (pGp120Ig) than in those transfected with the gp120 and Ig-gp120 expression plasmids (pGp120 and pIgGp120, respectively). pGp120Ig elicited more HIV-specific CD8 T cells and effector memory CD8 T cells than pGp120 in immunized mice. Furthermore, pGp120Ig significantly reduced the viral load after challenge with an HIV Env gp160-expressing vaccinia virus. These results demonstrate that covalent antigen modification with an Ig sequence can modulate antigen-specific cellular immune responses. The approach may be useful for vaccine development.     

Influenza A (H5N1) Viruses from Pigs, Indonesia

Pigs have long been considered potential intermediate hosts in which avian influenza viruses can adapt to humans. To determine whether this potential exists for pigs in Indonesia, we conducted surveillance during 2005–2009. We found that 52 pigs in 4 provinces were infected during 2005–2007 but not 2008–2009. Phylogenetic analysis showed that the viruses had been introduced into the pig population in Indonesia on at least 3 occasions. One isolate had acquired the ability to recognize a human-type receptor. No infected pig had influenza-like symptoms, indicating that influenza A (H5N1) viruses can replicate undetected for prolonged periods, facilitating avian virus adaptation to mammalian hosts. Our data suggest that pigs are at risk for infection during outbreaks of influenza virus A (H5N1) and can serve as intermediate hosts in which this avian virus can adapt to mammals.     

Intussusception due to rectal adenocarcinoma in a young adult: A case report

An intussusception due to colonic adenocarcinoma has sometimes been reported. However, to the best of our knowledge, reports of intussusception due to rectal adenocarcinoma are extremely rare. In this report, the case of a young man with rectal adenocarcinoma causing intussusception is described. A 24-year-old man visited a hospital complaining of abdominal pain, and an upper rectal cancer was diagnosed by colonoscopy. Computed tomography showed intussusception caused by a large tumor in the pelvis and absence of distant metastases. Locally advanced rectal cancer causing intussusception was diagnosed, and a low anterior resection was performed. Intraoperatively, repair of the invagination could not be accomplished easily; therefore, the repair was abandoned. Instead, the tumor was removed en bloc to avoid dissemination of the cancer. Histopathologically, the tumor was diagnosed as a poorly differentiated adenocarcinoma, pStage IIA. The patient has no evidence of recurrence at 10 mo after the operation.     

Prevention of esophageal strictures after endoscopic submucosal dissection

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have recently been accepted as less invasive methods for treating patients with early esophageal cancers such as squamous cell carcinoma and dysplasia of Barrett’s esophagus. However, the large defects in the esophageal mucosa often cause severe esophageal strictures, which dramatically reduce the patient’s quality of life. Although preventive endoscopic balloon dilatation can reduce dysphagia and the frequency of dilatation, other approaches are necessary to prevent esophageal strictures after ESD. This review describes several strategies for preventing esophageal strictures after ESD, with a particular focus on anti-inflammatory and tissue engineering approaches. The local injection of triamcinolone acetonide and other systemic steroid therapies are frequently used to prevent esophageal strictures after ESD. Tissue engineering approaches for preventing esophageal strictures have recently been applied in basic research studies. Scaffolds with temporary stents have been applied in five cases, and this technique has been shown to be safe and is anticipated to prevent esophageal strictures. Fabricated autologous oral mucosal epithelial cell sheets to cover the defective mucosa similarly to how commercially available skin products fabricated from epidermal cells are used for skin defects or in cases of intractable ulcers. Fabricated autologous oral-mucosal-epithelial cell sheets have already been shown to be safe.     

Pancreaticoduodenectomy following total gastrectomy:A case report and literature review

We present a case of afferent loop syndrome(ALS)occurring after pancreaticoduodenectomy(PD)in a patient who had previously undergone total gastrectomy(TG),and review the English-language literature concerning reconstruction procedures following PD in patients who had undergone TG.The patient was a69-year-old man who had undergone TG reconstruction by a Roux-en-Y method at age 58 years.The patient underwent PD for pancreas head adenocarcinoma.A jejunal limb previously made at the prior TG was used for pancreaticojejunostomy and hepaticojejunostomy.Despite normal patency of the hepaticojejunostomy,he suffered from repeated postoperative cholangitis which was brought on by ALS due to shortness of the jejunal limb(15 cm in length).We therefore performed receliotomy in which the hepaticojejunostomy was disconnected and reconstructed using a new Y limb 40-cm in length constructed in a double Roux-en-Y fashion.The refractory cholangitis resolved immediately after the receliotomy and did not recur.Review of the literature revealed the lack of any current consensus for a standard procedure for reconstruction following PD in patients who had previously undergone TG.This issue warrants further attention,particularly given the expected future increase in the number of PDs in patients with a history of gastric cancer.     

ARB affects nicotine-induced gene expression profile in human coronary artery endothelial cells

AIM: To investigate the effects of nicotine and nicotine plus angiotensin II receptor blocker (ARB) on the gene expression profile of human coronary artery endothelial cells (HCAECs). METHODS: The changes in gene expression profiles in HCAECs treated with nicotine and nicotine plus ARB olmesartan were analyzed by DNA microarray. In nicotine-treated HCAECs, 432 genes selected by P < 0.01 were greater than 1.5-fold compared with the untreated cells. Data were analyzed using IPA (Ingenuity^® Systems, www.ingenuity.com). RESULTS: The gene expression levels of tumor necrosis factor-α, collagen type 1, matrix metalloproteinase-10, and disintegrin and metalloprotease domain 8, which are related to “cardiovascular function and disease”, were significantly increased. In canonical pathway analyses using IPA, “atherosclerosis signaling” was strongly affected by nicotine treatment and this effect was reduced by co-incubation with ARB olmesartan. These data indicate that the deleterious cardiovascular consequences of cigarette smoking may, at least in part, be due to the nicotine-induced gene expression profile related to “atherosclerosis signaling”. CONCLUSION: The inhibitory effect of ARB against the nicotine-induced gene expression profile may possibly induce anti-atherosclerotic effects that are independent of those from lowering the blood pressure.     

Development of a nomogram for predicting a positive repeat prostate biopsy

AIM: To fi nd risk factors of cancer in patients who had a repeat biopsy and to develop the nomogram using our cohort. METHODS: Among 3500 patients who had a prostate biopsy over 11 years between 2000 and 2010 at our hospital, we studied a total of 807 repeat biopsy sessions in 459 patients who had at least 1 initial negative biopsy. At each biopsy session, we recorded patient age, number of previous biopsy sessions, number of biopsy cores, number of previously negative biopsy cores, months from the initial biopsy, months from the previous biopsy, serum PSA, PSA slope, digital rectal examination fi ndings, hypoechoic lesions suspicious for a cancer on transrectal ultrasonography, total prostate volume, transitional zone(TZ) volume, PSA density, PSA TZ density and history of high grade prostatic intraepithelial neoplasia(HGPIN) or atypical small acinar proliferation(ASAP). Clinical and pathological variables were correlated with the outcome of repeat biopsies. A nomogram was developed based on logistic regression analyses and calibration was performed.RESULTS: Overall, 17% of repeat biopsies had a cancer. With receiver operating characteristics analyses, the highest area under the curve(AUC) was obtained based on all available 13 variables, which were age, PSA, digital rectal examination, PSA density, prostate volume, TZ volume, PSA TZ density, cumulative number of biopsy cores, HGPIN, ASAP, months from previous negative biopsy, initial negative biopsy and number of biopsy cores. Based on multivariable logistic regression analysis, a nomogram was constructed with an AUC of 0.74, which was greater than that of any single risk factor. The calibration plot seemed to be good.CONCLUSION: Our nomogram for predicting a positive repeat biopsy can provide probabilities for cancer and may help clinical judgment on whether to do a repeat prostate biopsy.     

Cell sheet technology for regeneration of esophageal mucosa

The progress of tissue-engineering technology has realized development of new therapies to treat various disorders by using cultured cells. Cell- and tissue-based therapies have been successfully applied to human patients, and several tissue-engineered products have been approved by the regulatory agencies and are commercially available. In the review article, we describe our experience of development and clinical application of cell sheet-based regenerative medicine. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been shown to be useful for removal of gastrointestinal neoplasms with less invasiveness compared with open surgery, especially in esophageal surgery. However, postoperative inflammation and stenosis are major complications observed after intensive mucosal resection. Therefore, we have developed novel regenerative medicine to prevent such complications and promote wound healing of esophageal mucosa after EMR or ESD. Transplantable oral mucosal epithelial cell sheets were fabricated from patients’ own oral mucosa. Immediately after EMR or ESD, fabricated autologous cell sheets were endoscopically transplanted to the ulcer sites. We performed a preclinical study with a canine model. In human clinical settings, cell culture and cell sheet fabrication were performed in clean rooms according to good manufacturing practice guidelines, and pharmaceutical drugs were used as supplements to culture medium in place of research regents used in animal study. We believe that cell-based regenerative medicine would be useful to improve quality of life of patients after EMR or ESD.     

Ultra-high-molecular-weight Polyethylene (UHMWPE) Wing Method for Strong Cranioplasty

We developed a new cranioplasty method that utilizes artificial bone made of ultra-high-molecular-weight polyethylene, with a wedge-shaped edge (UHMWPE Wing). This study shows the methods and data of case series and finite element analyses with the UHMWPE Wing. A circumferential wing was preoperatively designed for a custom-made artificial bone made of UHMWPE to achieve high fixed power and to minimize the usage of cranial implants. Here, we present 4 years of follow-up data and finite element analyses for patients treated with the UHMWPE Wing between February 2015 and February 2019. Eighteen consecutive patients underwent cranioplasty using our UHMWPE Wing design. There were no postoperative adverse events in 17 of the patients for at least 18 months. One case of hydrocephalus experienced screw loosening and graft uplift due to shunt malfunction. Placement of a ventriculo-peritoneal shunt immediately returned the artificial bone to normal position. Finite element analyses revealed that a model using the UHMWPE Wing had the highest withstand load and lowest deformation. This is the first report on the UHMWPE Wing method. This method may enable clinicians to minimize dead space and achieve high strength in cranioplasty.     

Reconstructive surgery for recurrent penile curvature

Purpose

There are surprisingly few reports about reconstructive surgery for severe recurrent/persistent penile curvature (redo-PC). We present our experience.

Methods

We reviewed 9 redo-PC cases we treated between 1998 and 2016.

Results

Cases 1–3 and 5 were identified from 111 consecutive hypospadias patients we treated between 1998 and 2016 (4/111; 3.6%). Cases 4 and 6–9 had initial surgery elsewhere. Initial PC was severe (>?45°; n?=?5), moderate (30°-45°; n?=?1), or unknown (n?=?3), treated by dorsal plication (DP) in 4/9 (cases 1–4), chordectomy in 2/9 (cases 5, 6), and unknown in 3/9 (cases 7–9); no case had tunica albuginea incision (TAI). Straightening after initial surgery was confirmed by artificial erection (AE) in 4/9, not confirmed (2/9), and unknown (3/9). Cases 1, 2, 7 and 8 had had previous failed redos. Scarring of buccal mucosa used for urethroplasty caused worse PC in cases 7 and 9. After TAI (n?=?6; cases 1, 3–6, and 8) or scar removal with DP (n?=?3; cases 2, 7, and 9), AE confirmed successful straightening in all cases, without sequelae after a mean follow-up of 2.6 years.

Conclusion

TAI was most effective for redo-PC surgery. Preoperative AE and examination under anesthesia should be used to customize treatment.