Pituitary stalk interruption syndrome broadens the clinical spectrum of the TTC26 ciliopathy.

Ciliopathies are a heterogeneous group of disorders, related to abnormal ciliary function. Severe biliary ciliopathy, caused by bi-allelic mutations in TTC26, has been recently described in the context of a syndrome of polydactyly and severe neonatal cholestasis, with brain, kidney and heart involvement. Pituitary involvement has not been previously reported for patients with this condition. Pituitary stalk interruption syndrome (PSIS) is a congenital anomaly of the pituitary gland, diagnosed by characteristic MRI findings. We now describe four patients with TTC26 ciliopathy due to a homozygous c.695A>G p.Asn232Ser mutation and delineate PSIS as a novel clinical feature of this disorder, highlighting an important role of TTC26 in pituitary development.

Automated Analyzers Are Suited for Diagnosing Celiac Disease Without a Biopsy.

OBJECTIVES: The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2012 guidelines, enabled for the first time, a nonbiopsy approach in the diagnosis of celiac disease (CD). We aimed to prospectively assess 4 tissue-transglutaminase (tTg) IgA assays of 4 random-access analyzers and examine their accuracy in diagnosing CD without a biopsy. METHODS: We enrolled 186 consecutive children referred to upper endoscopy and intestinal biopsy. One group included 109 patients with positive tTg that was referred for suspected CD. Another group included 77 patients with negative tTg referred because of other indications. All participants had a blood sample taken at the time of endoscopy. Samples were tested with 4 tTg IgA assays on automated analyzers and 1 Elisa kit. All intestinal biopsies were evaluated by a local pathologist, a central pathologist, and a CD expert blinded to each other. CD was diagnosed when full agreement was reached. Analytical performance of the assays included precision with controls and samples, lot to lot variation, and carryover. RESULTS: In our cohort, all tested tTg IgA-automated assays showed sensitivities above 98% and specificities above 99%. ROC analysis demonstrated AUC (area under the curve) >0.99 for all 4 analyzers. The positive-predictive values (PPV) were all >0.99 and negative-predictive values (NPV) were >0.97. The Elisa kit had sensitivity of 95%, specificity of 96%, AUC of 0.96, PPV of 0.98 and NPV of 0.93. CONCLUSION: CD can be accurately diagnosed without biopsy based on tTg IgA levels at least 10 times the ULN using the 4 high-volume random-access analyzers used in our study.

Nose biopsy: a comparison between two sampling techniques.

Pre operative biopsy is important in obtaining preliminary information that may help in tailoring the optimal treatment. The aim of this study was to compare two sampling techniques of obtaining nasal biopsy-nasal forceps and nasal scissors in terms of pathological results. Biopsies of nasal lesions were taken from patients undergoing nasal surgery by two techniques- with nasal forceps and with nasal scissors. Each sample was examined by a senior pathologist that was blinded to the sampling method. A grading system was used to rate the crush artifact in every sample (none, mild, moderate, severe). A comparison was made between the severity of the crush artifact and the pathological results of the two techniques. One hundred and forty-four samples were taken from 46 patients. Thirty-one were males and the mean age was 49.6 years. Samples taken by forceps had significantly higher grades of crush artifacts compared to those taken by scissors. The degree of crush artifacts had a significant influence on the accuracy of the pre operative biopsy. Forceps cause significant amount of crush artifacts compared to scissors. The degree of crush artifact in the tissue sample influences the accuracy of the biopsy.

Uncommon Detection of Leiomyoma in the Penile Corpus Spongiosum Using FDG PET/CT: A Case Report.

ABSTRACT: Primary tumors of the penile corpus spongiosum are rare. Hereby we describe the scintigraphic findings of a case of penile leiomyoma within the corpus spongiosum tissue, which was incidentally detected on FDG PET/CT. The benign neoplasm was growing in close proximity to the urethra showing increased focal FDG uptake on sequential PET/CT studies. Subsequently, the patient experienced obstructive urinary symptoms, and the tumor was resected. We concluded that the possibility of neoplasm should be kept in mind while evaluating a patient with persistent focal penile FDG uptake, which may be the first and only manifestation of the disease.

Mycophenolate Mofetil Alone and in Combination with Tacrolimus Inhibits the Proliferation of HT-29 Human Colonic Adenocarcinoma Cell Line and Might Interfere with Colonic Tumorigenesis.

BACKGROUND/AIM: Familial adenomatous polyposis (FAP) was found to be completely reversed in a patient treated with mycophenolate mofetil (MMF) and tacrolimus following kidney transplantation. In this preliminary study, we assessed whether MMF and tacrolimus alone or in combination interfere with the cell cycle and proliferation in a human colonic adenocarcinoma cell line and in the colonic polyps of the patient with FAP. MATERIALS AND METHODS: Human colonic adenocarcinoma HT-29 cells were treated with tacrolimus and MMF alone and in combination at different concentrations. Cell viability and proliferation were assessed using the MTT assay. Cell-cycle distribution was analyzed by flow cytometry. Expression of Ki-67, a marker of mitotic activity, was evaluated in the patient's colonic polyps before and under drug treatment. RESULTS: MMF in combination with tacrolimus induced S-phase cell-cycle arrest and markedly inhibited HT-29 cell proliferation. Ki-67 expression in the patient's colonic polyps was significantly reduced following combined tacrolimus and MMF treatment. CONCLUSION: MMF and tacrolimus synergistically inhibited proliferation of a human colonic adenocarcinoma cell line and interfered with the expansion of colonic crypt proliferation in the polyp from a patient with FAP. The results confirm our clinical observation and indicate the possibility of novel approach to therapy of colorectal neoplasia.

Complete Reversion of Familial Adenomatous Polyposis Phenotype Associated with Tacrolimus and Mycophenolate Mofetil Treatment Following Kidney Transplantation.

Numerous germline mutations in the adenomatous polyposis coli (APC) tumor-suppressor gene are responsible for development of multiple adenomatous colorectal polyps with their inevitable progression to cancer. Multiple attempts at dietary and pharmacological prevention of colorectal carcinoma development in patients with familial adenomatous polyposis (FAP) have provided conflicting results. Immunosuppressive treatment with tacrolimus is known to be associated with an increased risk of malignancy and should be avoided in patients with high propensity for development of neoplasia. We observed a complete reversion of FAP phenotype in a male teenager carrying a germline mutation in APC gene who underwent a kidney transplant due to end-stage kidney disease secondary to congenital dysplastic kidneys. The patient was treated with tacrolimus and mycophenolate mofetil after transplantation. The possible chemopreventative role of these agents should be evaluated and confirmed in a larger cohort. The elucidation of molecular mechanisms underpinning the observed chemopreventative effect of tacrolimus and mycophenolate mofetil might lead to the development of a novel colorectal cancer therapy.

Examining the safety of colon anastomosis on a rat model of ischemia-reperfusion injury.

INTRODUCTION: Intestinal ischemia and reperfusion can impair anastomotic strength. The purpose of this study was to evaluate the safety of delayed colon anastomosis following remote ischemia-reperfusion (IR) injury. METHODS: Rats divided into two groups underwent bilateral groin incisions, however only the study group had femoral artery clamping to inflict IR injury. Twenty-four hours following this insult, the animals underwent laparotomy, incision of the transverse colon and reanastomosis. End points included anastomotic leakage, strength and histopathological features. RESULTS: Anastomotic leak among IR animals (22.2%) was not statistically different in comparison to the controls [10.5% (p = 0.40)]. Anastomotic mean burst pressures showed no statistically significant difference [150.6 ± 15.57 mmHg in the control group vs. 159.9 ± 9.88 mmHg in the IR group (p = 0.64)]. The acute inflammatory process in the IR group was similar to controls (p = 0.26), as was the chronic repair process (p = 0.88). There was no significant difference between the inflammation:repair ratios amongst the two groups (p = 0.67). CONCLUSION: Primary colon repair is safe when performed 24 hours following systemic IR injury.

Infectious diseases are analogous with cancer. Hypothesis and implications.

We propose to disclose first degree analogous features between cancer and infectious diseases and to find out whether these similarities are superficial and negligible, due to the use of the same bodily pathways by the two categories of disease or if they represent significantly parallel characteristics. We have found several primary analogous features, predominantly regarding pathways of spread, but to some extent also concerning the interaction with the immune system. Some of the implications to our hypothesis are probably available in the recent literature, at the experimental or clinical levels. For example endostatin, an angiogenic inhibitor has been used to prevent promotion of metastasis in cancer and to reduce granulomas formation in schistosomiasis. An ECFR antagonist employed to restrain bronchial vessels proliferation in pseudomonas infection, has also been used for the treatment of lung cancer.