Treatment of patients with Graves' disease and the appropriate extent of thyroidectomy.

Graves' disease is an autoimmune disorder caused by thyroid stimulating auto-antibodies directed against the thyrotropin receptor on thyroid follicular cells. It is the most common cause of hyperthyroidism and is associated with cardiovascular, ophthalmologic and other systemic manifestations. Three treatment options are available for Graves' disease: anti-thyroid drugs, radioactive iodine and thyroidectomy. While thyroidectomy is the least common option used for treatment of Graves' disease, it is preferentially indicated for patients with a large goiter causing compressive symptoms, suspicious or malignant thyroid nodules or significant ophthalmopathy. The best operation for Graves' disease has been a matter of debate. The standard operation was a subtotal thyroidectomy for much of the twentieth century, however, over the past 20 years total thyroidectomy has been increasingly performed. Herein, we provide a historical perspective and review the current literature, including randomized controlled trials, systematic reviews and meta-analyses and conclude that total thyroidectomy is the preferred option for the surgical treatment of Graves' disease, with a nearly 0% recurrence rate, predictable postoperative hypothyroidism and a low complication rate comparable to subtotal thyroidectomy when performed by high-volume thyroid surgeons.

CCL3 augments tumor rejection and enhances CD8+ T cell infiltration through NK and CD103+ dendritic cell recruitment via IFNγ.

Inflammatory chemokines are critical contributors in attracting relevant immune cells to the tumor microenvironment and driving cellular interactions and molecular signaling cascades that dictate the ultimate outcome of host anti-tumor immune response. Therefore, rational application of chemokines in a spatial-temporal dependent manner may constitute an attractive adjuvant in immunotherapeutic approaches against cancer. Existing data suggest that the macrophage inflammatory protein (MIP)-1 family and related proteins, consisting of CCL3 (MIP-1α), CCL4 (MIP-1ß), and CCL5 (RANTES), can be major determinant of immune cellular infiltration in certain tumors through their direct recruitment of antigen presenting cells, including dendritic cells (DCs) to the tumor site. In this study, we examined how CCL3 in a murine colon tumor microenvironment, CT26, enhances antitumor immunity. We identified natural killer (NK) cells as a major lymphocyte subtype that is preferentially recruited to the CCL3-rich tumor site. NK cells contribute to the overall IFNγ content, CD103+ DC accumulation, and augment the production of chemokines CXCL9 and CXCL10 for enhanced T cell recruitment. We further demonstrate that both soluble CCL3 and CCL3-secreting irradiated tumor vaccine can effectively halt the progression of established tumors in a spatial-dependent manner. Our finding implies an important contribution of NK in the CCL3 - CD103+ DC - CXCL9/10 signaling axis in determining tumor immune landscape within the tumor microenvironment.

Is intraoperative parathyroid hormone monitoring necessary for primary hyperparathyroidism with concordant preoperative imaging?

BACKGROUND: The purpose of this study was to determine if intraoperative parathyroid hormone (PTH) monitoring is necessary in patients with concordant ultrasound and sestamibi imaging. METHODS: Clinical factors, intraoperative findings and outcome were correlated with imaging results in patients with primary hyperparathyroidism who underwent parathyroidectomy with concordant ultrasound and sestamibi imaging. RESULTS: There were 127 patients with primary hyperparathyroidism and concordant imaging who underwent parathyroidectomy. Seven patients (5.5%) had intraoperative findings that were discordant with imaging: 2 (1.6%) had an adenoma at a different location, 2 (1.6%) had double adenomas and 3 (2.4%) had asymmetric hyperplasia. Gland weight and preoperative PTH levels were greater for patients with concordant operative and imaging findings (p < 0.05). CONCLUSION: Six percent of patients with concordant ultrasound and sestamibi imaging had unexpected intraoperative findings. Intraoperative PTH monitoring remains a necessary adjunct even with concordant imaging to ensure identification of abnormal parathyroid glands and cure of hyperparathyroidism.

Oesophageal pseudodiverticulum after foregut duplication cyst excision: Case report and literature review.

Oesophageal pseudodiverticula rarely occur after excision of benign oesophageal neoplasms. While management and outcomes have been reported in the adult leiomyoma literature, sparse data exist on the occurrence and management of pseudodiverticula after foregut duplication cyst excision. We discuss our experience with a paediatric patient and review relevant literature regarding operative techniques and surgical outcomes.

Outcome differences between young children and adolescents undergoing kidney transplantation.

BACKGROUND/PURPOSE: Although graft loss remains the biggest challenge for all pediatric kidney transplant (KT) recipients, unique challenges exist within different age groups. We aim to evaluate the different characteristics and graft survival outcomes of young children and adolescents undergoing KT. METHODS: Children who underwent isolated KT between 2000 and 2013 at our institution were included in this retrospective analysis. Patient characteristics and outcomes were compared using student's t-test, chi-square test, Kaplan-Meier curve and Cox proportional hazards model. RESULTS: Of 73 children who underwent KT, 31 were <12 (young children), and 42 were ≥ 12 years old (adolescents). Overall patient survival was 100%. The younger group had superior 5-year (100% vs. 75.5%) and 10-year (94.4% vs. 43.8%) graft survival (p=0.008). Factors predictive of poor graft survival on multivariate analysis were older age at transplantation (HR 1.2, CI 1-1.4, p=0.047), female gender (HR 9.0, CI 1.9-43, p=0.006), and acute rejection episodes (HR 13, CI 2-90, p=0.008). The most common causes of graft loss were acute and chronic rejection episodes and immunosuppression nonadherence. CONCLUSION: Adolescents undergoing KT have inferior graft survival compared to younger children. In adjusted modeling, children with older age, female gender, and acute rejection episodes have inferior graft survival.

Transcontinental telementoring with pediatric surgeons: proof of concept and technical considerations.

PURPOSE: To evaluate different technologies that can facilitate telementoring in a variety of pediatric surgical procedures. MATERIALS AND METHODS: Two different telementoring technologies were used to provide two-way audio and visual communication between experienced pediatric surgeon mentors located in another city and less experienced trainees performing a surgical procedure. The first technology consisted of store-bought equipment that connected the operating room laparoscope to a Skype™ (Microsoft, Redmond, WA) connection (used in 1 case), whereas the second was a proprietary telementoring robot, Karl Storz Endoscopy-America, Inc. VisitOR1(®) (Karl Storz GmbH & Co. KG, Tuttlingen, Germany) (used in 5 cases). The procedures included a video-assisted thoracic surgery lower lobectomy, a temporary and two permanent gastric stimulator placements, and two laparoscopic inguinal hernia repairs and were performed by pediatric surgeons (3 cases), a pediatric gastroenterologist (1 case), and a general surgeon (2 cases) under the guidance of pediatric surgeon mentors. RESULTS: All procedures were completed successfully in a time-efficient manner, without loss of transmission and without complications. Although the Skype technology was less costly, it lacked telestrator capacity and was not adequately secure. The VisitOR1 telementoring robot enabled high-resolution video communication, had telestrator capacity, and allowed pointing during the procedure. The mentors assisted with trocar placement, modifying the surgical technique, identifying planes of dissection, and indicating locations of device and suture placement. CONCLUSIONS: Telementoring is a useful adjunct in the field of pediatric surgery that can aid in the transfer of surgical skills remotely and shorten the time to implementation of new surgical techniques into practice. Optimal telementoring technology should have a secure wireless connection, high video resolution, and minimal bandwidth latency.

Factors influencing disease recurrence after ileocolic resection in adult and pediatric onset Crohn's disease.

BACKGROUND: Factors influencing recurrence of ileocecal Crohn's disease (CD) after surgical resection may differ between adolescents and adults. METHODS: CD patients who underwent ileocecectomy were retrospectively divided into pediatric onset (age at diagnosis ≤ 16 years, n = 34) and adult onset (>16, n = 108) patients to evaluate differences in risks of endoscopic and clinical recurrence. RESULTS: In 142 patients, rates of any recurrence, endoscopic recurrence, and clinical recurrence at 5 years were 78%, 88%, and 65%, respectively. Risks of recurrence were similar between groups. Younger patients were more likely to be on immunologics preoperatively and more likely to be started on immunoprophylaxis postoperatively. Immediate postoperative prophylaxis was predictive of delayed clinical recurrence only in the older group. CONCLUSIONS: Despite increased preoperative and postoperative immunoprophylaxis in younger patients, recurrence rates of CD after ileocecectomy do not differ between these groups. Immediate postoperative prophylaxis was predictive of delayed clinical recurrence only in patients with adult onset CD.

Murine leukemia virus envelope gp70 is a shared biomarker for the high-sensitivity quantification of murine tumor burden.

The preclinical development of anticancer drugs including immunotherapeutics and targeted agents relies on the ability to detect minimal residual tumor burden as a measure of therapeutic efficacy. Real-time quantitative (qPCR) represents an exquisitely sensitive method to perform such an assessment. However, qPCR-based applications are limited by the availability of a genetic defect associated with each tumor model under investigation. Here, we describe an off-the-shelf qPCR-based approach to detect a broad array of commonly used preclinical murine tumor models. In particular, we report that the mRNA coding for the envelope glycoprotein 70 (gp70) encoded by the endogenous murine leukemia virus (MuLV) is universally expressed in 22 murine cancer cell lines of disparate histological origin but is silent in 20 out of 22 normal mouse tissues. Further, we detected the presence of as few as 100 tumor cells in whole lung extracts using qPCR specific for gp70, supporting the notion that this detection approach has a higher sensitivity as compared with traditional tissue histology methods. Although gp70 is expressed in a wide variety of tumor cell lines, it was absent in inflamed tissues, non-transformed cell lines, or pre-cancerous lesions. Having a high-sensitivity biomarker for the detection of a wide range of murine tumor cells that does not require additional genetic manipulations or the knowledge of specific genetic alterations present in a given neoplasm represents a unique experimental tool for investigating metastasis, assessing antitumor therapeutic interventions, and further determining tumor recurrence or minimal residual disease.

Chemokines as Cancer Vaccine Adjuvants.

We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs) and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.