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IL-37 is a newly discovered cytokine belonging to IL-1 family consisting of 11 members, which have similar β-barrel structures and associate with Ig-like receptors. Extensive studies have been done with IL-37 since its discovery. These studies suggest that IL-37 does not only play a role in tumorigenesis, but also has anti-inflammatory properties in immune responses through the down regulation of pro-inflammatory molecules. We have previously reviewed the role of IL-37 in cancer. Here, we will focus on the role of IL-37 in non-cancerous Diseases. Such a study might be helpful to design new strategies to treat IL-37 associated diseases.

Highlights • IL-29 activates the JAK-STAT signaling pathway through STAT1 and STAT2. • IL-29 can either induce tumor promoting effects or tumor inhibiting effects depending on the cancer cell type being affected. • IL-29 could be a potential therapeutic target in cancer treatment., Interleukin-29 (IL-29) is a new member of the recently discovered interferon λ (IFNλ) family. It is produced predominantly by maturing dendritic cells and macrophages. It has been implicated in numerous immunological responses and has shown antiviral activity similar to the Type I interferons, although its target cell population is more limited than the Type I interferons. In recent years, the role of IL-29 in the pathogenesis of various cancers has also been extensively studied. In this review, we will discuss the recent advances of IL-29 in immunological processes and the pathogenesis of various cancer.

Introduction After a failed transplant, management of a non-functional graft with pain or recurrent infections can be challenging. Transplant nephrectomy (TN) can be a morbid procedure with the potential for significant blood loss. Embolization of the renal artery alone has been proposed as a method of reducing complications from an in vivo failed kidney transplant. While this does yield less morbidity, it may not address an infected graft or refractory hematuria or rejection. We elected to begin preoperative embolization to assess if this would help decrease the blood loss and transfusion rate associated with TN. Materials and Methods We performed a retrospective analysis of all patients who underwent non-emergent TN at our institution. Patients who had functioning grafts that later failed were included in analysis. TN was performed for recurrent infections, pain or hematuria. We evaluated for blood loss (EBL) during TN, transfusion rate and length of hospital stay. Results A total of 16 patients were identified. Nine had preoperative embolization or no blood flow to the graft prior to TN. The remaining 7 did not have preoperative embolization. The shortest time from transplant to TN was 8 months and the longest 18 years with an average of 6.3 years. Average EBL for the embolized patients (ETN) was 143.9cc compared to 621.4cc in the non-embolized (NETN) group (p=0.041). Average number of units of blood transfused was 0.44 in the ETN with only 3/9 patients requiring transfusion. The NETN patients had average of 1.29 units transfused with 5/7 requiring transfusion. The length of stay was longer for the ETN (5.4 days) compared to 3.9 in the NETN. No intraoperative complications were seen in either group and only one patient had a postoperative ileus in the NETN. Conclusion Embolization prior to TN significantly decreases the EBL but does not significantly decrease transfusion rate. However, patients do require a significantly longer hospitalization with embolization due to the time needed for embolization. Larger studies are needed to determine if embolization before transplant nephrectomy reduces the transfusion rates and overall complications.

This study determined if a SystemCHANGE™ intervention was more efficacious than attention control in increasing immunosuppressive medication adherence and improving outcomes in adult kidney transplant recipients during a 6-month intervention phase and subsequent 6-month (no intervention) maintenance phase. The SystemCHANGE™ intervention taught patients to use person-level quality improvement strategies to link adherence to established daily routines, environmental cues, and supportive people. Eighty-nine patients (average age 51.8 years, 58% male, 61% African American) completed the 6-month intervention phase. Using an intent-to-treat analysis, at 6 months, medication adherence for SystemCHANGE™ (median 0.91, IQR 0.76-0.96) and attention control (median 0.67, IQR 0.52-0.72) patients differed markedly (difference in medians 0.24, 95% CI 0.13-0.30, P < .001). At the conclusion of the subsequent 6-month maintenance phase, the gap between medication adherence for SystemCHANGE™ (median 0.77, IQR 0.56-0.94) and attention control (median 0.60, IQR 0.44-0.73) patients remained large (difference in medians 0.17, 95% CI 0.06-0.33, P = .004). SystemCHANGE™ patients evidenced lower mean creatinine and BUN at 12 months and more infections at 6 and 12 months. This first fully powered RCT testing SystemCHANGE™ to improve and maintain medication adherence in kidney transplant recipients demonstrated large, clinically meaningful improvements in medication adherence. Clinical Trial Registration: NCT02416479.

Pancreatic cancer is the most lethal digestive cancer and the fourth leading cause of cancer death in the US. IL-39, a heterodimer of p19 and EBI3, is a newly found cytokine and its role in the pathogenesis of neoplasia has not been studied yet. This study was designed to investigate the direct role of IL-39 in the growth of pancreatic cancer. Clonogenic survival assay, cell proliferation, and caspase-3 activity kits were used to evaluate the direct effects of IL-39 on cell survival, proliferation and apoptosis of the widely studied pancreatic cancer cell line MiaPaCa-2. We further investigated the possible molecular mechanisms by using RT-PCR and IHC. The percentage of colonies of pancreatic cancer cells increased significantly in the presence of IL-39. This was paralleled with the increase in the OD value of cancer cells in the presence of IL-39. Interestingly, the relative caspase-3 activity in cancer cells decreased significantly in the presence of IL-39. Furthermore, the pro-tumor effect of IL-39 on pancreatic cancer cells correlated with decreased anti-proliferative molecule p21.The anti-apoptotic effect of IL-39 correlated with decreased pro-apoptotic molecule TRAILR1. These results suggest that IL-39 favors growth of pancreatic cancer by promoting growth and inhibiting apoptosis of cancer cells. This suggests that IL-39 acts as a friend to pancreatic cancer. Thus, inhibition of effect of IL-39 on cells might be a promising strategy to treat pancreatic cancer.

Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase-3 activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunocytochemistry. It was determined that the HCT-116 cells demonstrated an notable decrease in optical density value upon incubation with IL-33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti-proliferative effect of IL-33 on HCT-116 cells was associated with downregulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing effect of IL-33 on HCT-116 cells was associated with downregulation of the anti-apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken together, the results indicated that IL-33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.

Ovarian cancer is the leading cause of cancer‑ associated mortality in the female reproductive system. Interleukin (IL)‑33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by many cell types including epithelial cells. The role of IL‑33 in the pathogenesis of neoplasia remains controversial. The authors previously demonstrated that IL‑33 inhibits the growth of pancreatic cancer cells. The present study was performed to explore if IL‑33 has any direct effects on ovarian cancer cells. A clonogenic survival assay, immunohistochemistry (IHC), proliferation kit and caspase‑3 activity kit were all used to evaluate the direct effects of IL‑33 on cell proliferation and apoptosis of a widely studied ovarian cancer cell line, A2780. The possible molecular mechanisms were further evaluated with reverse transcription‑polymerase chain reaction and IHC. It was demonstrated that the percentage of colonies and the optical density value of cancer cells were all increased in the presence of IL‑33; however, the relative caspase‑3 activity in cancer cells was decreased in the presence of IL‑33. Molecular mechanism studies revealed that the pro‑proliferative effect of IL‑33 on cancer cells was associated with decreased levels of p27, and the anti‑apoptotic effect of IL‑33 was associated with levels of Fas cell surface death receptor (Fas) and tumor necrosis factor‑related apoptosis‑inducing ligand receptor 1 (TRAILR1). Therefore, IL‑33 promoted proliferation and inhibited apoptosis of ovarian cancer cells by downregulation of p27, Fas and TRAILR1. Contrary to previous studies demonstrating an anti‑tumor effort in pancreatic cancer, the results of the present study indicated that IL‑33 exhibited a significant onco‑promoting effect on ovarian cancer. Accordingly, the inhibition of IL‑33 may be a promising therapeutic strategy for ovarian cancer.

Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the USA. Radiation therapy (RT) is widely considered the standard treatment for PCa. IL-37 is an IL-1 family member, and it has been extensively studied in immunity. However, no studies have been done regarding its potential as a radiosensitizer. This study is designed to investigate the direct effect of IL-37 on growth of DU145 and PC-3, two widely studied PCa cell lines, and to investigate whether IL-37 could be used as a radiosensitizer for PCa. Clonogenic survival and quick cell proliferation assays along with immunohistochemistry, TUNEL staining, and caspace-3 activity assay kits as well as RT-PCR were used in this study. Our results showed that IL-37 has little direct effect on growth of PCa. However, IL-37/RT enhanced RT-induced inhibition of cell proliferation and apoptosis in both cell lines. We further found that IL-37/RT upregulated the mRNA expression of p27, Fas, and Bax, while downregulating the mRNA expression of cdk2 in DU145 cells. These findings suggest that IL-37 has the potential to be used as a radiosensitizer for PCa and warrants further investigation.

Nearly 40% of men and women will be diagnosed with cancer during their lifetime. Thus, there is a rapidly growing need for novel therapies to combat this deadly disease. One such method is the consumption of blueberries. Long coveted for their powerful antioxidant properties, more recent studies have demonstrated that blueberries also exhibit inherent abilities to prevent carcinogenesis, inhibit the proliferation of neoplastic cells, and reduce the risks of recurrence in patients in remission. This review will focus on the specific activities of blueberry derivatives in cancer cells across many different forms of cancer. Ultimately, such research could be helpful in the development of new strategies to treat cancer.

Adolescent idiopathic scoliosis (AIS) is a deformity of the spine of unknown etiology and no definitive cure. A novel technique for correction during growth known as vertebral body tethering (VBT) was introduced in 2005 in animal models, and then quickly adapted for human implementation [Courvoisier, 2015]. This method is in the early stages of growth and adaptation as well as evaluating risks to improve safety and feasibility. Some of the most common complications reported are atelectasis [Newton, 2018], proximal junctional kyphosis and reoperation for device breakage or addition [Hardesty, 2017]. There are no case reports describing ureteral injury following VBT. We present a case of primary ureteral injury following VBT with subsequent erosion and stricture formation requiring definitive ureteral reconstruction. We discuss the possible causes of this complication, its management, follow up, and short-term outcome. Keywords: Vertebral body tethering, Surgical complication, Ureteral injury

This study examined patterns, potential predictors, and outcomes of immunosuppressive medication adherence in a convenience sample of 121 kidney transplant recipients aged 21 years or older from three kidney transplant centers using a theory-based, descriptive, correlational, longitudinal design. Electronic monitoring was conducted for 12 months using the Medication Event Monitoring System. Participants were persistent in taking their immunosuppressive medications, but execution, which includes both taking and timing, was poor. Older age was the only demographic variable associated with medication adherence (r = 0.25; p = 0.005). Of the potential predictors examined, only medication self-efficacy was associated with medication non-adherence, explaining about 9% of the variance (r = 0.31, p = 0.0006). The few poor outcomes that occurred were not significantly associated with medication non-adherence, although the small number of poor outcomes may have limited our ability to detect a link. Future research should test fully powered, theory-based, experimental interventions that include a medication self-efficacy component.

Interleukin-7 (IL-7) is a cytokine that has been known since long in immunology, mainly regarding its effects on T-cells and B-cells. IL-7 has been demonstrated to be necessary for both B-cell and T-cell proliferation and lack of IL-7 causes immature immune cell arrest. Interestingly, in recent years, certain studies have strongly suggested that the role of IL-7 is far beyond the field of immunology, it might have direct or indirect effect on cancer. This review aims to summarize the role of IL-7 in immunity and its role in the pathogenesis of neoplasia.

IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2. We found that the percentage of colonies of MIA PaCa-2 cells, PCNA+ cells and the OD value of cancer cells were all decreased in the presence of IL-33. TUNEL+ cells and the relative caspase-3 activity in cancer cells were increased in the presence of IL-33. We further found that its anti-proliferative effect on cancer cells correlated with downregulation of pro-proliferative molecules cdk2 and cdk4 and upregulation of anti-proliferative molecules p15, p21 and p53. Its pro-apoptotic effect correlated with downregulation of anti-apoptotic molecule FLIP and upregulation of pro-apoptotic molecule TRAIL. These results suggest that IL-33 presents significant anti-tumor effects by inhibition of proliferation and induction of apoptosis of MIA PaCa-2 pancreatic cancer cells. Thus, strength of IL-33/ST2 signal pathway might be a promising way to treat pancreatic cancer.

Melanoma is the leading cause of death among all skin cancers and its incidence continues to rise rapidly worldwide in the past decades. The available treatment options for melanoma remain limited despite extensive clinical research. Melanoma is an immunogenic tumor and great advances in immunology in recent decades allow for the development of immunotherapeutic agents against melanoma. In recent years, immunotherapy utilizing cytokines has been particularly successful in certain cancers and holds promise for patients with advanced melanoma. In this review, an overview of the current status and emerging perspectives on cytokine immunotherapy for melanoma are discussed in details. Such a study will be helpful to unveil the mysterious mask of cytokine-based immunotherapy for melanoma.

Prostate cancer (PCA) is the most common malignancy in men in USA, and the role of Trichomonas vaginalis (T. vag) in the development of PCA is still controversial. Clonogenic assay, PCNA staining, TUNEL staining and caspase-3 activity assay were used to investigate the in vitro role of T. vag in human prostate cancer. We further investigated the possible molecular mechanisms using RT-PCR and immunohistochemical staining. Culture supernatant of T. vag inhibits growth of PC-3 prostate cancer cells, and this correlated with upregulation of p21. Culture supernatant of T. vag induced apoptosis of PC-3 cells, and this correlated with downregulation of Bcl-2. The growth inhibition effect of culture supernatant of T. vag is also demonstrated in another prostate cancer cell line DU145, suggesting that its effect is not specific to one prostate cancer cell line. Culture supernatant of T. vag inhibits growth of prostate cancer by inhibition of proliferation and promotion of apoptosis. Such a study might be helpful to address the association between PCA and infection of T. vag.

Acinetobacter baumannii has been becoming a great challenge to clinicians due to their resistance to almost all available antibiotics. In this study, we sequenced the genome from a multiple antibiotics resistant Acinetobacter baumannii stain which was named A. baumannii-1isolated from China by SMRT sequencing technology to explore its potential mechanisms to antibiotic resistance. We found that several mechanisms might contribute to the antibiotic resistance of Acinetobacter baumannii. Specifically, we found that SNP in genes associated with nucleotide excision repair and ABC transporter might contribute to its resistance to multiple antibiotics; we also found that specific genes associated with bacterial DNA integration and recombination, DNA-mediated transposition and response to antibiotics might contribute to its resistance to multiple antibiotics; Furthermore, specific genes associated with penicillin and cephalosporin biosynthetic pathway and specific genes associated with CHDL and MBL β-lactamase genes might contribute to its resistance to multiple antibiotics. Thus, the detailed mechanisms by which Acinetobacter baumannii show extensive resistance to multiple antibiotics are very complicated. Such a study might be helpful to develop new strategies to control Acinetobacter baumannii infection.

Prostate cancer (PCa) is the most common non-cutaneous cancer in the United States. There is currently a lack of safe and effective radiosensitizers that can enhance the effectiveness of radiation treatment (RT) for Pca. Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining and caspase-3 activity assay were used to assess proliferation and apoptosis in DU145 Pca cells. RT-PCR/IHC were used to investigate the mechanisms. We found that the percentage of colonies, PCNA staining intensity, and the optical density value of DU145 cells were decreased (RT/GT vs. RT). TUNEL + cells and the relative caspase-3 activity were increased (RT/GT vs. RT). Compared to RT, the anti-proliferative effect of RT/GT correlated with increased expression of the anti-proliferative molecule p16. Compared to RT, the pro-apoptotic effect of RT/GT correlated with decreased expression of the anti-apoptotic molecule Bcl-2. GT enhances RT sensitivity of DU145 by inhibiting proliferation and promoting apoptosis.

Cervical cancer (CC) is a leading cause of death in women worldwide. Radiation therapy (RT) for CC is an effective alternative, but its toxicity remains challenging. Blueberry is amongst the most commonly consumed berries in the United States. We previously showed that resveratrol, a compound in red grapes, can be used as a radiosensitizer for prostate cancer. In this study, we found that the percentage of colonies, PCNA expression level and the OD value of cells from the CC cell line SiHa were all decreased in RT/Blueberry Extract (BE) group when compared to those in the RT alone group. Furthermore, TUNEL+ cells and the relative caspase-3 activity in the CC cells were increased in the RT/BE group compared to those in the RT alone group. The anti-proliferative effect of RT/BE on cancer cells correlated with downregulation of pro-proliferative molecules cyclin D and cyclin E. The pro-apoptotic effect of RT/BE correlated with upregulation of the pro-apoptotic molecule TRAIL. Thus, BE sensitizes SiHa cells to RT by inhibition of proliferation and promotion of apoptosis, suggesting that blueberry might be used as a potential radiosensitizer to treat CC.

To investigate if γ-synuclein (SNCG) could be used as a bladder cancer (BC) marker to predict prognosis of BC.Medical records of 140 patients with BC (January, 2006 to December, 2009) were retrospectively reviewed. SNCG expression level was examined by immunohistological staining. The patients' survival rate was calculated by the Kaplan-Meier method. Cox proportional regression model was used to identify independent predictors for BC.Overexpression of SNCG was detected in BC tissues and the expression level of SNCG strongly positively correlated with BC recurrence. However, no correlation was found between SNCG level and tumor stage or survival rate.SNCG is a good marker to predict recurrence of BC, but not a reliable marker for staging or prediction of survival rate.

Background Immunosuppressive medication non-adherence is one of the most prevalent but preventable causes of poor outcomes in adult renal transplant recipients, yet there is a paucity of studies testing interventions in this area. Methods Using a randomized controlled trial design, 30 adult renal transplant recipients were screened for medication non-adherence using electronic monitoring. Fifteen non-adherent participants were randomized to receive either a continuous self-improvement intervention or attention control management. The six-month continuous self-improvement intervention involved the participant and clinical nurse specialist collaboratively identifying the person's life routines, important people, and possible solutions to enhance medication taking. The participant then received individual monthly medication taking feedback delivered via a graphic printout of daily medication taking generated from electronic monitoring. Results The mean medication adherence score for the continuous self-improvement intervention group (n = 8) was statistically significantly higher than the attention control group's (n = 5) mean medication adherence score (p = 0.03). The continuous self-improvement intervention effect size (Cohen's d) was large at 1.4. Participants' perceptions of the intervention were highly favorable. Conclusions The continuous self-improvement intervention shows promise as an effective and feasible approach to improve medication adherence in adult renal transplant recipients. A fully-powered study with a diverse sample is needed to confirm these preliminary findings.

This project examined patterns, predictors, and outcomes of medication adherence in a convenience sample of 37 renal transplant recipients aged 55 years or older in a Mid-Southern U.S. facility using an exploratory, descriptive, longitudinal design. Electronic monitoring was conducted for 12 months using the Medication Event Monitoring System. An alarming 86% of the participants were nonadherent with medications. Four clusters of medication taking and timing patterns were identified with evening doses presenting particular challenges. Depression, self-efficacy, social support, and medication side effects did not predict medication adherence. There was no significant difference in medication adherence scores between those with and without infections. Medication adherence pattern data from electronic monitoring provides an opportunity for health care professionals to move away from blaming the patient by attempting to identify predictors for medication nonadherence. Medication dose taking and timing patterns could be explored with patients so that medication adherence interventions could target specific patient patterns.

Riley J, Troxel S, Wakefield M, Ross G, Weinstein S. Laparoscopic donor nephrectomy – safety in a small-volume transplant center. Clin Transplant 2010: 24: 429–432. © 2009 John Wiley & Sons A/S. Abstract: Introduction: Laparoscopy is a standard surgical option for live donor nephrectomy (LDN) at the majority of transplant centers. Equivalent graft survival with shorter convalescence has been reported by several large volume centers. With the arrival of an experienced laparoscopic surgeon in 2002, we began to offer laparoscopic LDN at our institution. We report our experience as a large volume laparoscopic surgery program but a low volume transplant center. Methods: A retrospective review of the previous 34 LDN (17 open, 17 laparoscopic) performed at the University of Missouri were included. A single laparoscopic surgeon performed all laparoscopic procedures. Hand assisted laparoscopy was performed in 15 and standard laparoscopy with a pfannenstiel incision in two. Open procedures were performed through anterior subcostal or flank incision. A single surgeon performed all open procedures. Results: There was no statistical difference in age, body mass index or American Society of Anesthesiologies Score between the two groups. Mean operative time, estimated blood loss and hospital stay were 229 minutes, 324 cc and 2.2 days respectively in the laparoscopic group compared to 202 minutes, 440 cc and five days for the open group. Average warm ischemia time was 179 seconds. Recipient creatinine for the two groups at one week, one month and one year was not statistically significantly different. Each group had one graft loss due to medication noncompliance. Conclusion: For small transplant centers with an advanced laparoscopic program, laparoscopic LDN is a safe procedure with comparable outcomes to major transplant centers.

Background: At the University of Missouri School of Medicine (MUSOM), ‘‘commitment to improving quality and safety in healthcare’’ is one of eight key characteristics set as goals for our graduates. As educators, we have modelled our commitment to continuous improvement in the educational experiences through the creation of a method to monitor and analyse patient encounters in the third year of medical school. This educational improvement project allowed course directors to (1) confirm adequate clinical exposure, (2) obtain prompt information on student experiences, (3) adjust individual student rotations to meet requirements and (4) ascertain the range of clinical experiences available to students. Discussion: Data illustrate high levels of use and satisfaction with the educational innovation. We are in our second year using the new Patient Log (PLOG) process and are now considering expanding the use of PLOG into the fourth year of medical school.

The long-term outcome of kidneys transplanted from blood group A(2) live donors into blood group O or B candidates is not known. From 1986 through 2006, we transplanted eight blood group O patients and one blood group B patient with kidneys from blood group A(2) live donors. Immunosuppression was no different for these patients than for ABO-compatible recipients. All patients received methylprednisolone, cyclosporine or tacrolimus and azathioprine or mycophenolate mofetil with or without antibody induction (monoclonal or polyclonal). Of the nine live-donor A(2) to O and B transplants performed, seven grafts remain functioning. One of those seven was lost to follow-up at 9.2 years with a functioning kidney. Of the remaining six patients, length of follow-up is 10.4, 6.5, 5.3, 4, 2.1 and 1 years. Of the two patients who lost their grafts, one died with a functioning graft (DWFG) at 8.8 years and one lost his graft at 13.2 years due to noncompliance with immunosuppression. These data show that good long-term graft survival can be expected in live-donor A(2) to O and B transplantation despite some of those patients experiencing the type of clinical problems seen with ABO-compatible transplants.

In recent years, attention has focused on the prognostic importance of neuroendocrine differentiation in prostate cancer. Focal neuroendocrine differentiation in prostatic adenocarcinoma is a frequent finding. Though controversial, the prevalence of neuroendocrine cells has been correlated with higher-grade malignancy and poor prognosis. As with other small cell tumors, production of ectopic neuropeptides has been reported. The rarity of the disease has precluded prospective randomized trials. Therapeutic regimens have mainly been modeled after those for small cell lung carcinoma. Here we review the literature to identify potential diagnostic, therapeutic, and prognostic factors. Evident from this review is the necessity for further research in the biology of small cell carcinoma progression, in order to improve therapy.

Interleukin-11 (IL-11) is a member of the glycoprotein-130 (GP-130) cytokines that utilizes the GP-130 signaling pathway shared by other cytokines of the same family. Traditionally regarded as an anti-inflammatory cytokine, IL-11 also demonstrates its role as a proinflammatory cytokine, suggesting its complex role in immune response. In recent years, IL-11 has an emerging role in various inflammation-associated cancers. In this review, we aim to discuss IL-11 signaling pathway, to explore the role of IL-11 in immunity and various cancers, and to provide a therapeutic perspective of strategies utilized to interfere IL-11 signaling in cancer cells.

Interleukin-10 (IL-10) produced by a wide-variety of cells is a highly pleiotropic cytokine. It has been implicated in the pathogenesis and/or development of autoimmune diseases and cancer, although it displays differential effects that seem to be contradictory sometimes. The ultimate role of this cytokine in disease, however, cannot be fully determined until the immunological contexts that regulate its function are further elucidated. In this review, we will discuss a wide variety of evidence of IL-10 in immunity and cancer in an effort to illuminate the remaining mysteries in the function of this cytokine that, when fully understood, may prove to be a powerful tool in the battle against cancer.

531 Background: Ablative treatments achieve good oncological outcome for renal parenchymal tumors 3 cm or smaller. Larger renal malignancies are increasingly being treated with ablation. This comparative study determines the survival following ablation in these large renal masses. Methods: Patients undergoing cryotherapy or thermal ablation (Procedure codes 13, 15, or 23) for renal tumors were identified from SEER database (1998-2013). Exclusions: T stage not recorded, more than one primary, metastatic, or node positive disease. Demographics, stage, and overall (OS) and cancer specific survival (CSS) were analyzed. T1a tumors were compared to T1b or T2 tumors. Tumors 3 cm or less were compared to greater than 3 cm. Results: 4886 patients were identified, and 2340 patients met inclusion criteria. The mean age was 66.5 years, 1943 were white, 243 were black, and 1419 were male. The stage distribution included T1a (n=2159), T1b (n=172), and T2 (n=9). 1186 tumors had right sided, 1149 had left ,and the others were bilateral or not specified. 2326 patients had the size recorded and 1637 patients had 3 cm or smaller tumors and 689 tumors were larger than 3 cm. The OS in T1a tumors was 84.4% at 5 years and 69.2% at 9 years. The patients with T1b tumors had 62% at 5 years and 38% at 9 years. The T2 tumors had an OS of 64.8% at 57 months. The 5 yr CSS was 97.4% in the whole group, 97.9% in T1a, and 97.4% in the T1b group. The corresponding 9 yr CSS was 96.9, 97.5, and 96.9%. Comparative CSS in patients with T1a tumors was 98% at 5 years and 97.5% at 9 years. In T1b or greater tumors the 5 and 9 year survival was 90.2%. All patients that survived beyond 5 years were alive at 9 years of follow-up. On analysis by size, tumors 3 cm or less had a 98.4 5-yr and a 98.2 9-yr CSS and tumors that were greater than 3 cm had 95% 5-yr and a 93.9 9-yr survival. On univariate analysis both T1a tumors and tumors smaller than 3 cm had significantly better survival (p=0.001). Conclusions: Ablative therapies for small renal masses can achieve excellent CSS at 97% at 9 years. This study demonstrates that reasonable CSS can be achieved in masses larger than 3 cm and patients with T1b or larger tumors. Further studies are required to address the role of ablative therapies for larger renal masses.

Background/Purpose: The optimal surgical technique for orchiopexy is controversial. Studies have shown that adequate fixation can be obtained using a subdartos pouch alone; however, transparenchymal suture fixation with a permanent suture frequently is used to provide additional security and for the treatment and prevention of testicular torsion. In previous studies, the suture has been placed through the tunica albuginea. This could have a detrimental effect on future spermatogenesis. Polypropylene has been shown to have the least histological change and is considered to be the suture of choice. However, polypropylene is a stiff suture and can be disconcerting for the patient when left in place. Polytetrafluoroethylene (PTFE) is a soft, permanent suture used widely in vascular surgery because of its handling characteristics. In this study, the authors compare the histological changes caused by PTFE and polypropylene. Methods: Bilateral orchiopexies were performed in 36 Sprague-Dawley rats. All rats were 27 to 31 days old and weighed 75 to 100 g at the time of orchiopexy. The animals were divided into 3 groups receiving polypropylene and PTFE, silk and PTFE, or polypropylene and silk. After 30 days, all rats were killed, and the testes were harvested. The testes were step sectioned and examined for histological changes. These changes were graded by a pathologist in a blinded fashion. Results: The data obtained were statistically analyzed. The superficial histological changes associated with transparenchymal fixation by polypropylene, PTFE, and silk were significantly different, but the parenchymal changes were not. Conclusions: PTFE causes no greater histological change than polypropylene. In light of the PTFE's softness and superior handling characteristics, the authors recommend the use of PTFE when a permanent suture is used in orchiopexy.

495 Background: This was a retrospective review analyzing the epidemiological and pathological association of penile cancer as well as the clinical results in patients managed at the University of Missouri Hospital and Clinics (UMHC) and Harry S Truman VA. Methods: Records were obtained of patients with a pathological diagnosis of penile cancer from 2001−2014 at UMHC and at the Harry S Truman VA. These charts were retrospectively reviewed. Information regarding patient demographics, pathology, treatment, and outcomes were recorded. Results: Forty-four patients with a pathologic diagnosis of penile cancer were identified. Mean age at diagnosis was 64 with 41 being White, 2 unknown, 1 Black, and 1 Hispanic. Seventy-two percent had tobacco exposure, with 66% of all patients having smoked greater than 10 years. HPV was present in 20%. Circumcision status was reviewed showing overall 61% were circumcised, with 4.5% being circumcised before the age of 18. Premalignant lesions were identified in 36% of the patients, with condyloma acuminate being the most common followed by Lichen Sclerosus and severe dysplasia. The vast majority (98%) of penile cancers were squamous cell carcinoma (SCCa), with only one patient having a Buschke−Lowenstein tumor. Invasive SCCa without nodal involvement was the most common pathologic stage (41%) followed by nodal positive disease (36%) and CIS (23%). Of those with node positive disease, 56% were dead less than 5 years after nodal involvement. Ninety-nine procedures with curative intent were performed, with a mean of 2.25 procedure per patient. However, only 79 of the procedures led to a sustainable cure. Of those patients with metastatic disease 13.6% underwent chemotherapy and 9.1% received radiation. Conclusions: Our study reflects the trends in stage, recurrence, treatment, and outcomes at two large centers for penile cancer. In this patient group the majority had exposure to tobacco and almost exclusively had SCCa. A durable cure may require multiple operative interventions. Nodal involvement carries a poor prognosis and high risk of death in less than 5 years once diagnosed.

Objective The aim of the study was to determine whether a standardized orientation to basic laparoscopy makes a positive effect on the experience of third-year medical students. Study Design Fifty-three third-year medical students at the University of Missouri, Columbia were randomly divided into 2 groups during their clerkship orientation. Both groups received a 40-minute laparoscopic hands-on training simulation guided by instructors. However, only 1 group was given a 20-minute multimedia presentation on introduction to laparoscopy that covered equipment, set up, troubleshooting, and different methods of access into the abdomen. Both groups were given a preclerkship and postclerkship survey where students were asked to rate their experience, comfort, and interest in surgery on a 10-point Likert scale. Results Hundred percent of the students receiving the combined hands-on training simulation and the 20-minute presentation felt that the experience helped during their clerkship (p = 0.002) and 92% felt it had a positive effect (p = 0.501). In contrast, only 72% of the group that received the hands-on training simulation alone found it helpful (p = 0.029) and 86% thought it had a positive effect (p = 0.508). There was no statistical difference between either group with regard to their perceived comfort with assistance in the operating room and with laparoscopy. Neither experience had a statistical effect on a students' interest in surgery as a career. Conclusions Our results demonstrate how a standardized orientation to basic laparoscopy can make a positive effect on a student's experience; however, it fails to transition into a student's interest in surgery as a profession or in their perceived comfort level in the operating room. Our study suggests that a student's surgical interest is highly variable and composed of multiple experiences that occur during their clerkship that ultimately affects their perception of surgery as a field and profession.

The combination of bladder exstrophy and gastroschisis has not been reported previously. The authors describe this rare combination of congenital anomalies, as well as the successful multidisciplinary management of this unusual problem.

Bryan CF, Luger AM, Smith JL, Warady BA, Wakefield M, Schadde E, Murillo D, Nelson PW. Sharing kidneys across donor-service area boundaries with sensitized candidates can be influenced by HLA C. Clin Transplant 2010: 24: 56–61. © 2009 John Wiley & Sons A/S. Abstract: The United Network for Organ Sharing (UNOS) implemented the virtual crossmatch system in UNet as a way to improve the likelihood of a negative crossmatch when kidneys are shared with HLA-sensitized candidates across donor service area (DSA) boundaries. The role of HLA C in that process is not universally appreciated. We recently experienced an unexpected positive flow T and B cell crossmatch for an imported, HLA zero-mismatched kidney because of donor-specific HLA C antibodies and transplanted it into the backup candidate. HLA C locus antigens were not typed by the OPO’s laboratory that sent the kidney so the UNet virtual crossmatch could not “strike” our candidate from the UNOS match run. HLA C locus typing data of donors for kidneys our DSA imported from other DSAs revealed that C typing was not performed in 23% (14/60) and was discrepant with our molecular type for 10% (6/60) and was concordant in 67% (40/60) of cases. The rate of positive donor-specific crossmatches was higher (83%) for HLA C discrepantly typed donors than for concordantly typed donors (44%). Sensitization for HLA C (42%) is less frequent than for A (80%) or B (83%) locus antigens but the immunogenicity of C locus antigens in patients who make C locus antibodies is equivalent in black and white patients. Finally, the transplant rate of imported kidneys into class I-sensitized candidates was 24%, and C locus-sensitized candidates comprised 55% of those transplanted.

This study evaluated older renal transplant recipients’ perceptions of electronic medication monitoring and the influence of these perceptions on medication adherence. A sample of 73 older adult renal transplant recipients who used the Medication Event Monitoring System (MEMS®) TrackCaps for 12 months provided their perceptions of device use. Participants perceived that the MEMS had a neutral effect on their medication-taking routine (65%), believed the MEMS was practical (56%), and could not describe any instances in which using the MEMS was difficult (56%). No significant difference in medication adherence was found between those who perceived the MEMS’s influence negatively/neutrally and those who perceived the MEMS positively (p = 0.22). Medication adherence data from older adult renal transplant recipients can be used regardless of their perceptions of the MEMS’s influence on their medication taking without biasing medication adherence data.

Introduction: The influence of a positive B-cell crossmatch on graft outcome in renal transplantation is controversial. Methods: We analyzed graft survival using Kaplan–Meier estimates for recipients of deceased donor kidneys who were either regraft transplant patients (n = 198) from 1990 to August 20, 2004, or primary transplant patients (n = 361) from December 15, 2000 to August 8, 2004, each of whom had a flow T- and B-cell IgG crossmatch performed before transplantation. The flow B-cell crossmatch (FBXM) was not used to decide whether or not to transplant. Graft survival was analyzed by whether the patient's FBXM was positive or negative. We also evaluated creatinine levels and graft survival of 131 transplant patients (June 1, 2004 to July 1, 2005) by their FBXM result and by their HLA class II flow-defined IgG PRA. Results: One- and three-yr graft survival for the primary transplant patient group with a positive FBXM (98% and 84%) was not significantly different from the group with a negative FBXM (96% and 93%) (log-rank = 0.9). Similarly, graft survival at one, five, and 10 yr for the regraft transplant group whose FBXM was positive (91%, 76%, and 61%) was not significantly different from the group whose FBXM was negative (91%, 79%, and 77%) (log-rank = 0.4). Creatinine levels in the group of patients whose FBXM was positive (1.4 ± 0.4 mg/dL; n = 76) were not significantly different from the group with a negative FBXM (1.4 ± 0.4 mg/dL; n = 42). Even in the presence of class II PRA, a positive FBXM did not impact a patient's creatinine levels or graft outcome. Conclusion: Neither short nor long-term graft survival of deceased donor kidneys is influenced by a positive flow B-cell IgG crossmatch, even when caused by HLA class II antibody.