Niv Pencovich

The development of endometriosis in a murine model is dependent on the presence of dendritic cells.

Endometriosis is a common condition associated with pelvic pain and infertility. This study group has previously shown that supplementation of dendritic cells led to enhancement of endometriosis lesion growth and angiogenesis. This study determined whether endometriosis is dependent on the presence of endogenous dendritic cells. Surgical induction of endometriosis was performed in CD11c⁺ DTR/GFP transgenic (Tg) female mice in which dendritic cells were ablated upon injection of diphtheria toxin (DT). Mice were allocated into four groups (n=5 each): group I, wild-type mice treated with vehicle; group II, wild-type mice treated with DT; group III, Tg mice treated with DT; and group IV, Tg mice treated with vehicle. After 10 days, mice were killed and endometriosis lesions were analysed by flow cytometry. DT treatment led to ablation of dendritic cells in spleens and endometriosis lesions in Tg mice while no ablation was observed in controls. Corresponding to dendritic cell ablation, endometriosis lesions in group III were ∼5-fold smaller than in the control groups (ANOVA P<0.0001). This study suggests that endometriosis development is dependent on the presence of endogenous dendritic cells. Therapies designed to inhibit dendritic cell infiltration as possible treatments for endometriosis warrant further study.

Resection of colorectal liver metastases in the elderly—Is it justified?

Liver resection of colorectal liver metastasis (CRLM) may necessitate large metabolic and physiologic reserve. As the population ages, resection of CRLM is increasingly required in the elderly. We assessed the safety and efficacy of these operations.

Atypical meningioma as a solitary malignancy in a patient with Rothmund-Thompson syndrome.

Background: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by genomic instability and increased risk of various malignancies, especially osteosarcoma and squamous cell carcinoma. We report the first RTS patient who developed a central nervous system (CNS)-related neoplasm. Case description: A 28-year-old male, previously diagnosed with RTS , developed a massive parasagital lesion, detected by magnetic resonance imaging. The tumor was surgically removed and histologically diagnosed as atypical meningioma. Preoperative symptoms were dramatically improved. Conclusions: This is the first description of a CNS-related malignancy in RTS patients. Although rare, the genomic instability and additional risk factors of this syndrome should be considered in choosing the course of treatment.

Massive cystic dilatation within a tethered filum terminale causing cauda equina compression and mimicking syringomyelia in a young adult patient.

BackgroundThe ventriculus terminalis (VT) is formed during early embryonic development of the spinal cord and can only be identified histologically in both children and adults. Cystic dilatation of the VT can be seen in young children, but it rarely persists through adulthood.Clinical caseWe describe a 27-year-old female with paraparesis secondary to a massive and tethered cystic dilatation of the VT mimicking syringomyelia. Symptoms appearing in early childhood were ignored, probably leading to the much prominent presentation in early adulthood. The preoperative presentation and surgical treatment are discussed in relation to childhood history.ConclusionsAlthough extremely rare, symptomatic dilatation of the VT can be seen in young adults, usually with previous manifestations in early childhood. This entity should be considered while treating tethered cord spectrum.

Augmented expression of RUNX1 deregulates the global gene expression of U87 glioblastoma multiforme cells and inhibits tumor growth in mice

Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern. Overexpression of RUNX1 led to diminished tumor growth in nude and severe combined immunodeficiency mouse xenograft tumor model. At the molecular level, RUNX1 occupied thousands of genomic regions and regulated the expression of hundreds of target genes, both directly and indirectly. RUNX1 occupied genomic regions that corresponded to genes that were shown to play a role in brain tumor progression and angiogenesis and upon overexpression led to a substantial down-regulation of their expression level. When overexpressed in U87 glioblastoma multiforme cells, RUNX1 down-regulated key pathways in glioblastoma multiforme progression including epithelial to mesenchymal transition, MTORC1 signaling, hypoxia-induced signaling, and TNFa signaling via NFkB. Moreover, master regulators of the glioblastoma multiforme mesenchymal phenotype including CEBPb, ZNF238, and FOSL2 were directly regulated by RUNX1. The data suggest a central role for RUNX1 as master regulator of gene expression in the U87 glioblastoma multiforme cell line and mark RUNX1 as a potential target for novel future therapies for glioblastoma multiforme.

Laparoscopic sleeve gastrectomy for diabetics – 5-year outcomes

OBJECTIVE Although the laparoscopic sleeve gastrectomy (SG) is increasingly performed for morbid obesity, gastric bypass is still considered by many to be the gold standard procedure for obese diabetic patients. The aim of this study was to assess the long-term results of SG in morbidly obese patients with type 2 diabetes. METHODS Diabetic patients who underwent SG at a single center between 2009 and 2011 were included. Outcomes assessed included postoperative complications, weight loss, and resolution or improvement in co-morbidities with an emphasis on diabetes, including glycated hemoglobin (HbA1C) and medication status. RESULTS Fifty-one diabetic patients underwent SG, 35 females and 16 males, with a collective mean age of 49 years and a mean body mass index of 43.2 kg/m2. On average, patients had had diabetes for 5.4 ± 7.3 years before surgery. Mean HbA1C and fasting glucose levels were 7.9 ± 1.6% and 166.9 ± 63 mg/dL, respectively. Eleven patients (22%) were insulin dependent at the time of surgery. Average body mass index at a mean follow-up of 5 years after surgery was 34.4 ± 5.8 kg/m2, with an average HbA1C of 6.6 ± 1% and an average fasting glucose of 123 ± 60 mg/dL. Only 3 patients remained insulin dependent. CONCLUSION SG offers retainable weight loss results, accompanied by longstanding resolution or improvement of diabetes. Prospective, randomized controlled studies are warranted to better compare long-term outcomes between SG and gastric bypass.

Diabetes resolution after one anastomosis gastric bypass

BACKGROUND Diabetes and other obesity-related diseases are a worldwide pandemic that transcends geographic borders as well as socioeconomic levels. Currently, it is well known that medical treatment alone is insufficient to ensure adequate and sustainable weight loss and co-morbidity resolution. It has been well proven that bariatric surgery can produce almost immediate resolution of diabetes and other co-morbidities as well as long-term weight loss. OBJECTIVES Here, we present our experience with the one anastomosis gastric bypass (OAGB) in terms of weight loss and diabetes resolution with 1 year of follow-up. SETTING Large, metropolitan, tertiary, university hospital. METHODS A retrospective analysis of all patients who underwent OAGB between March 2015 and March 2016 was performed. Patient demographic characteristics, co-morbidities, operative and postoperative data, as well as first year outcomes were collected and analyzed. RESULTS There were 407 patients who underwent OAGB (254 females, average age 41.8 ± 12.05 yr, body mass index = 41.7 ± 5.77 kg/m2). Of patients, 102 (25.1%) had diabetes with average glycosylated hemoglobin of 8.64 ± 1.94 g%, 93 (22.8%) had hypertension, 123 (28.8%) had hyperlipidemia, and 35 patients (8.6%) had obstructive sleep apnea. The average length of hospital stay was 2.2 ± .84 days (range, 2-10 d). The average excess weight loss 1 year after surgery was 88.9 ± 27.3. After 1 year, follow-up data were available for more than 85% of the studys general population. Of 102 diabetic patients, only 8 (7.8%) were still considered diabetic and taking antidiabetic medication, with an average glycosylated hemoglobin of 5.4 ± 0.6. CONCLUSIONS OAGB may be performed safely and with promising efficacy as both a primary and a revisional bariatric surgery, and it offers excellent resolution of diabetes.

Management of endoscopic retrograde cholangiopancreatography-related perforations: Experience of a tertiary center.

Background. Endoscopic retrograde cholangiopancreatography–induced perforation (EP) is a rare but severe complication. We describe the risk factors, management, and outcome of ERCP‐induced perforations in a tertiary center. Methods. This is a case‐control study. All EP cases between March 2004 and February 2015 were compared to a control group without perforation. Data on patients, procedures, presentation, perforation type, radiologic findings, management, and outcome were assessed. Results. Of 6,934 endoscopic retrograde cholangiopancreatographies, 37 patients (0.53%) had EP. Independent risk factors included failure of cannulation, a procedure described as “difficult,” performing a precut and resection of a periampullary adenoma. Perforation was diagnosed during the procedure in 7 patients (19%). Median interval for diagnosis was 11 hours (range: 0–201 hours), with 84% diagnosed within 30 hours. The periampullary region was the most common EP site (51%). Twenty‐nine patients (78%) were managed conservatively and 8 (22%) were operated. Three patients failed conservative management and required delayed operation. Failure of conservative management had a detrimental effect on morbidity and duration of stay. All patients who required operative intervention had perforation of either the duodenal free wall or the periampullary region. Conclusion. Clear risk factors can be used to raise suspicion of EP. Early diagnosis and management are critical for better outcome. This is especially important when operative intervention is indicated. Nonetheless, the majority of patients may be managed conservatively.