Programmed death-1 ligands and tumor infiltrating T lymphocytes in primary and lymph node metastasis of esophageal cancer patients.

Neoadjuvant chemotherapy (NAC) is administered to many patients with esophageal squamous cell carcinoma (ESCC) prior to surgery, but it is also true that some of these patients demonstrated no response to the therapy following surgery. In addition, the prognosis of advanced case such as ESCC patients with lymph node metastasis has remained relatively low. Programmed death ligand-1 (PD-L1) in conjunction with tumor-infiltrating lymphocytes (TILs) has been studied as a potential mechanism of "immune escape" in several human malignancies. Therefore, in this study, we studied PD-L1 status in carcinoma cells and forkhead box protein 3 (FOXP3) and CD8 status among TILs in the residual tumors of primary and metastatic sites following NAC. We also studied the association of these factors with the clinicopathological findings in 44 patients with ESCC harboring lymph node metastasis. There was discordance in the pathological response to chemotherapy between the primary tumor and lymph node metastasis, and histologically identified resistance to NAC in lymph node metastases tended to be correlated with an adverse clinical outcome (P = 0.0765) than resistance in the primary tumor. Both univariate and multivariate analyses for disease-specific survival (DSS) revealed that the PD-L1 status of carcinoma cells in metastatic lymph nodes and a higher FOXP3/CD8 ratio in the primary tumor were both significantly correlated with an eventual adverse clinical outcome of the patients (P = 0.0178, P = 0.0463, respectively). These results all indicated that the PD-L1 status of carcinoma cells in metastatic lymph nodes and the FOXP3/CD8 ratio in primary tumors could predict eventual clinical outcomes in ESCC patients with NAC.

Residual carcinoma cells after chemoradiotherapy for esophageal squamous cell carcinoma patients: striving toward appropriate judgment of biopsy.

In esophageal squamous cell carcinoma (ESCC) patients who are treated with chemoradiotherapy (CRT), identification of the presence or absence of residual or recurrent carcinoma is usually pivotal in their clinical management. In addition, the extent of carcinoma invasion into the esophageal wall could determine the clinical outcome of these patients following CRT. Therefore, in this study, we evaluated the response to CRT both macroscopically and histologically in a consecutive series of 42 ESCC patients receiving neoadjuvant chemoradiotherapy following curative esophageal resection at Tohoku University Hospital between August 2011 and December 2012. The histological grading of tumor regression was as follows: grade 3, markedly effective (no viable residual tumor cells); grade 2, moderately effective (residual tumor cells in less than one-third of the tumor); grade 1, slightly effective (1b, residual tumor cells in one-third to two-thirds of the tumor; 1a, residual tumor cells in more than two-thirds of the tumor); and grade 0, ineffective. In this study, we selected grade 2 and 1b cases because they might show a complete response with definitive CRT. We evaluated the presence of any residual in situ lesions and tumor depth in detail. The grading of tumor regression in primary sites was as follows: grade 3 (7 cases), grade 2 (16 cases), grade 1b (13 cases), and grade 1a (6 cases). The concordance rate between macroscopic and histopathological evaluation on the depth of the tumor was 40% (17/42). Among 29 cases (grade 2 and grade 1b), intraepithelial lesions were not detected in 17 cases, and tumor nests were not detected in the lamina propria mucosae in 9 cases. The results of this study highlight the difficulties of detecting residual carcinoma cells using conventional endoscopic biopsy in patients who have received CRT. Therefore, when residual cancer is clinically suspected in patients who have received CRT, the biopsy specimen should be obtained from the deep layer of the esophagus whenever possible. Additionally, close follow-up is required using positron emission tomography/computed tomography, endoscopy, and other radiological evaluations.

A laser-induced pulsed water jet for layer-selective submucosal dissection of the esophagus.

Background and aims: Conventional water jet devices have been used for injecting fluid to lift up lesions during endoscopic submucosal dissection or endoscopic mucosal resection procedures. However, these devices cannot dissect the submucosal layer effectively. Here we aim to elucidate the dissection capability of a laser-induced pulsed water jet and to clarify the mechanism of dissection with layer selectivity. Materials (Subjects) and methods: Pulsed water jets were ejected from a stainless nozzle by accelerating saline using the energy of a pulsed holmium: yttrium-aluminum-garnet laser. The impact force (strength) of the jet was evaluated using a force meter. Injection of the pulsed jet into the submucosal layer was documented by high-speed imaging. The physical properties of the swine esophagus were evaluated by measuring the breaking strength. Submucosal dissection of the swine esophagus was performed and the resection bed was evaluated histologically. Results: Submucosal dissection of the esophagus was accomplished at an impact force of 1.11-1.47 N/pulse (laser energy: 1.1-1.5 J/pulse; standoff distance: 60 mm). Histological specimens showed clear dissection at the submucosal layer without thermal injury. The mean static breaking strength of the submucosa (0.11 ± 0.04 MPa) was significantly lower than that of the mucosa (1.32 ± 0.18 MPa), and propria muscle (1.45 ± 0.16 MPa). Conclusions: The pulsed water jet device showed potential for achieving selective submucosal dissection. It could achieve mucosal, submucosal, and muscle layer selectivity owing to the varied breaking strengths.

Effectiveness of Bortezomib in a Patient With Acute Rejection Associated With an Elevation of Donor-Specific HLA Antibodies After Small-Bowel Transplantation: Case Report.

BACKGROUND: A significant association between donor-specific antibody (DSA) and graft rejection has recently been documented. However, confirmed strategy has not been established for DSA-associated rejection after intestinal transplantation (ITx). CASE REPORT: A 20-year-old male patient with chronic intestinal obstruction caused by hypoganglionosis of the entire intestine underwent cadaveric donor ITx with grafting performed on 232 cm of the small intestine, cecum, and a part of the ascending colon. On post-operative day (POD) 14, a histological evaluation showed an acute rejection of indeterminate grade. The patient had severe acute rejection on POD 16, which prompted us to administer bolus steroids and polyclonal anti-thymocyte antibody, along with baseline maintenance immunosuppression. The histopathological findings of the graft indicated typical acute cellular rejection, although C4d was positive. We then detected donor-specific HLA antibody. The patient initially responded well to the therapy and showed decreased histological rejection signs. However, the refractory low-grade rejection persisted in the graft. During this period, the patient showed increased levels of DSA, and we speculated that the persistent rejection was associated with DSA; thus, bortezomib was administered at this stage as a salvage therapy. This rejection was thereafter successfully controlled without severe adverse effect. Twenty-three months after ITx, the patient is currently alive with complete enteral autonomy. CONCLUSIONS: A case of acute graft rejection followed by a marked elevation of DSA is presented. In this particular case, a modified treatment protocol using bortezomib in addition to the typical immunosuppressive agents was effective.

Fibrosing cholestatic hepatitis developing within one month after living donor liver transplantation for chronic hepatitis C-related cirrhosis: a case report.

Fibrosing cholestatic hepatitis (FCH) is a life-threatening consequence of hepatitis C virus (HCV) infection occurring in a small minority of liver transplantation (LT) recipients. We herein report a case of early-onset FCH after living donor LT in a 47-year-old woman with HCV-related cirrhosis. The patient underwent balloon-occluded retrograde transvenous obliteration of a splenorenal shunt to treat an impaired portal flow on the sixth postoperative day (POD 6) and a bypass operation for hepatic artery thrombosis on POD 12. Thereafter, the serum bilirubin levels increased gradually; however, computed tomography revealed no evidence of biliary stricture. The serum HCV-RNA level on POD 27 was >7.8 log IU/mL. Histopathology of a needle graft biopsy performed on POD 28 revealed FCH with extensive portal fibrosis accompanied by mild inflammation, hepatocyte ballooning, and ductular proliferation with cholestasis. The patient received combination therapy with pegylated interferon, ribavirin, and double-filtration plasmapheresis for the treatment of early-onset FCH. Both the recipient and the donor carried the major genotype single nucleotide polymorphism (TT) at rs8099917 near the interleukin-28B gene. Furthermore, the HCV genotype was treatment-sensitive 2a. Nonetheless, the recipient died of hepatic failure on POD 211. Thus far, few cases of FCH occurring within 1 month after LT have been reported. In addition, the early onset of FCH may be an adverse prognostic factor.

Bilateral papillary renal cell carcinoma and angiomyolipoma in the patients with autosomal dominant polycystic kidney disease: case report of two cases and literature review.

We herein report two rare cases of bilateral renal neoplasms associated with autosomal dominant polycystic kidney disease (ADPKD). Case 1: Bilateral nephrectomy was performed on bilateral renal masses in a 58-year-old man with ADPKD. Case 2: Bilateral nephrectomy was performed on bilateral renal masses in a 32-year-old man with clinically suspected ADPKD. In case 1, angiomyolipoma (AML) and papillary renal cell carcinoma (PRCC) (type 1) were detected in the bilateral kidneys. In case 2, PRCC (type 1) was detected in the bilateral kidneys.

PTOV1: a novel testosterone-induced atherogenic gene in human aorta.

There are gender differences in the development of atherosclerosis, possibly owing to differences in sex steroid hormone action and/or metabolism. One of the atherogenic effects of testosterone is thought to be androgen receptor (AR)-mediated vascular smooth muscle cell (VSMC) proliferation. However, the detailed mechanism of this effect, particularly the identity of the genes associated with VSMC proliferation, remains largely unknown. Therefore, we first employed microarray analysis and, subsequently, quantitative RT-PCR to analyse RNA expression in AR-positive human VSMCs treated with testosterone in order to detect testosterone-induced genes associated with cell proliferation. We further examined whether the genes identified were involved in cell proliferation using small interfering RNA (siRNA) transfection. Expression of the gene products was then evaluated in human aorta with various degrees of atherosclerosis in order to evaluate the clinical relevance of the findings. Both microarray and quantitative RT-PCR analyses demonstrated marked induction of the human prostate overexpressed protein 1 (PTOV1) gene by testosterone in the cell lines: this gene was recently identified as a novel androgen-induced gene involved in prostate tumour cell proliferation. Inhibition of PTOV1 by transfection of its corresponding siRNA suppressed testosterone-induced cell proliferation. In human aorta, PTOV1 immunoreactivity in the nuclei of neointimal VSMCs was abundantly detected in male aorta with mild atherosclerotic changes compared with female aorta or male aorta with severe atherosclerotic changes. These findings indicate that the PTOV1 gene is androgen-responsive in VSMCs and that it may play an important role in androgen-related atherogenesis in the human aorta, particularly early atherosclerosis in the male aorta, through regulating proliferation of neointimal VSMCs.

Avaliaçäo do conhecimento sobre doenças sexualmente transmissíveis (DSTs) e síndrome da imunodeficiência adquirida (AIDS) entre universitários de Ribeiräo Preto/SP / Evaluation of the knowledge on sexually transmitted diseases (STDs) and acquired immunodeficiency syndrome (AIDS) among universitary students of Ribeiräo Preto/SP

Com o objetivo de avaliar o grau de conhecimento sobre DST/AIDS entre universitários de diferentes áreas, submeteu estudantes de uma faculdade de Ribeiräo Preto-SP a questionários com perguntas abertas e fechadas, anônimos após aquiescência. As respostas foram categorizadas como corretas (C), incorretas (I), entendimento incompleto (EI) e prejudicadas (P), sendo a análise realizada por porcentagens. De 1.200 estudantes, 961 (80,80 por cento) participaram do estudo. O número de respostas näo foi harmonioso para os diferentes itens do questionário. A área em que o aluno estava matriculado näo pareceu influenciar nas respostas. Com relaçäo à transmissäo do HIV, em 2.914 respostas obteve-se 65,37 por cento como categoria EI e em 923 (31,68 por cento) como C. Quanto a medidas preventivas contra a AIDS de 1888 respostas, 1.625 (86,07 por cento) como categoria C e 207 (10,96 por cento) como EI. Sobre medidas preventivas contra AIDS, utilizadas pelo aluno, 1.126 (74,42 por cento) como categoria C e 249 (16,46 por cento) e P. Quanto a medidas preventivas contra DSTs, 1.339 (71,11 por cento) como categoria C e 284 (15,80 por cento) obteve-se 1. Sobre medidas preventivas contra DSTs utilizadas pelo aluno, obteve-se 542 (43,92 por cento) como categoria C e 350 (28,36 por cento) como P. Os universitários em sua maioria parecem possuir um conhecimento teórico correto sobre as medidas preventivas contra à AIDS e DST e entendimento incompleto sobre a transmissäo do HIV. Provavelmente existem fatores relacionados à educaçäo ou culturais que impedem aos universitários fazerem uso das medidas preventivas que conhecem. Há necessidade de identificaçao desses fatores para que os programas de difusäo possam atingir os seus objetivos. A educaçäo continuada ainda se mostra necessária.