Inherited aplastic anemia with abnormal clones in bone marrow and increased endoreduplication in peripheral lymphocytes

Cytogenetic studies in peripheral blood and bone marrow cells from a female patient (aged 31 years) with inherited aplastic anemia and without other congenital anomalies are reported. Endoreduplication was increased in stimulated peripheral lymphocytes in several investigations. Chromosome breaks were shown to be near the control frequency, although chromatid exchange figures and dicentrics were present. Cytogenetic analysis was extended to the three children of our patient. Abnormal clones were detected in bone marrow preparations of our patient in all cytogenetic investigations. At the first examination, two of these clones were prevalent, with their karyotypes being 48,XX,+9,+16 and 46,XX,dup(1)(q24→q32),t(17;?)(p12–13;?). The prevailing karyotype after 2 years was 46,XX,t(17;?)(p12–13;?). Involvement of chromosomes #1 and #17 is discussed, taking into account data from the literature concerning several human neoplasias.     

Omentopexy with Glubran®2 for reducing complications after laparoscopic sleeve gastrectomy: results of a randomized controlled study

Background

Gastric fistulas, bleeding, and strictures are commonly reported after laparoscopic sleeve gastrectomy (LSG), that increase morbidity and hospital stay and may put the patient’s life at risk. We report our prospective evaluation of application of synthetic sealant, a modified cyanoacrylate (Glubran®2), on suture rime, associated with omentopexy, to identify results on LSG-related complications.

Methods

Patients were enrolled for LSG by two Bariatric Centers, with high-level activity volume. Intraoperative recorded parameters were: operative time, estimated intraoperative bleeding, conversion rate. We prospectively evaluated the presence of early complications after LSG during the follow up period. Overall complications were analyzed. Perioperative data and weight loss were also evaluated. A control group was identified for the study.

Results

Group A (treated with omentopexy with Glubran®2) included 96 cases. Control group included 90 consecutive patients. There were no differences among group in terms of age, sex and Body Mass Index (BMI). No patient was lost to follow-up for both groups. Overall complication rate was significantly reduced in Group A. Mean operative time and estimated bleeding did not differ from control group. We observed three postoperative leaks in Group B, while no case in Group A (not statistical significancy). We did not observe any mortality, neither reoperation. Weight loss of the cohort was similar among groups. In our series, no leaks occurred applying omentopexy with Glubran®2.

Conclusion

Our experience of omentopexy with a modified cyanoacrylate sealant may lead to a standardized and reproducible approach that can be safeguard for long LSG-suture rime.

Trial registration

Retrospective registration on clinicaltrials.gov PRS, with TRN NCT03833232 (14/02/2019).

     

DNA replication stress underlies renal phenotypes in CEP290-associated Joubert syndrome

Juvenile ciliopathy syndromes that are associated with renal cysts and premature renal failure are commonly the result of mutations in the gene encoding centrosomal protein CEP290. In addition to centrosomes and the transition zone at the base of the primary cilium, CEP290 also localizes to the nucleus; however, the nuclear function of CEP290 is unknown. Here, we demonstrate that reduction of cellular CEP290 in primary human and mouse kidney cells as well as in zebrafish embryos leads to enhanced DNA damage signaling and accumulation of DNA breaks ex vivo and in vivo. Compared with those from WT mice, primary kidney cells from Cep290-deficient mice exhibited supernumerary centrioles, decreased replication fork velocity, fork asymmetry, and increased levels of cyclin-dependent kinases (CDKs). Treatment of Cep290-deficient cells with CDK inhibitors rescued DNA damage and centriole number. Moreover, the loss of primary cilia that results from CEP290 dysfunction was rescued in 3D cell culture spheroids of primary murine kidney cells after exposure to CDK inhibitors. Together, our results provide a link between CEP290 and DNA replication stress and suggest CDK inhibition as a potential treatment strategy for a wide range of ciliopathy syndromes.     

A simplified procedure for continuous intraoperative external monitoring of systemic leakage during isolated limb perfusion

AIMS: Isolated limb perfusion (ILP) with high doses of an alkylating agent alone or in combination with tumor necrosis factor (TNF) in hyperthermic conditions (HAP) has been proposed for the treatment of locoregional tumors. A critical step in ILP/HAP is accurate monitoring of systemic leakage to prevent the toxic effects of chemotherapy, and in particular of TNF. Ten percent systemic leakage from the perfusion circuit is considered the maximum acceptable leakage. In this study we report our experience of a new leakage monitoring system. MATERIALS AND METHODS: Ths new simplified procedure is based on the use of 99mTc-labeled soluble human serum albumin (HSA) and a hand-held gamma probe as detector. The procedure consists of the following steps: 1) A standardized 99mTc-HSA dose of 0.5 MBq/kg body weight is injected into the perfusion circuit before chemotherapy/TNF perfusion and a hand-held gamma probe (IGP) is placed over the precordial area in a zone that was marked on the skin during a simulation test; 2) 48-72 hours before ILP/HAP a complete simulation test is performed with a 99mTc-HSA dose corresponding to 10% of the total dose calculated for the patient's body weight; 3) during the simulation test the maximum count-rate zone on the precordial area is detected by IGP and marked on the patient's skin; 4) a 60-min curve of effective 99mTc-HSA radioactivity decay (physical and biological) is calculated and fitted; 5) to compare external counting with the effective circulating radioactivity, patient blood samples and circuit blood samples are taken every five minutes during ILP/HAP and measured by a laboratory gamma counter and very convenient thanks to the favorable characteristics of IGP. The placed in the operating room. RESULTS: External counting with a hand-held gamma probe was easy to perform time/activity curves obtained during simulation tests showed a regular and constant effective decay with a mean decay rate of 30% at 60 minutes compared to baseline values. The external measurements obtained by IGP proved to be well correlated with blood samples measured in vitro by a laboratory gamma counter. The results of this procedure, in particular the data of the simulation test for each patient, allowed us to correct the limit of 10% maximum leakage during ILP/HAP in accordance with the time/activity curve. CONCLUSIONS: Although 99mTc-HSA has some unfavorable characteristics, it offers many advantages over 131I-HSA. The procedure proposed by us, which was based on the use of an IGP and 99mTc-HAS at a standardized dose of 0.5 MBq/kg body weight and on an individual simulation test for each patient performed 48 hours before ILP/HAP, proved to be simple and accurate in monitoring systemic leakage during ILP/HAP anti-cancer therapy.     

TSH pituitary adenoma: case report

We describe a rare case of thyroid-stimulating hormone-secreting pituitary adenoma in a patient with a clinical picture of hyperthyroidism, that developed bitemporal hemianopsia after four years of a known thyroid dysfunction. CT scan showed a pituitary tumor considered grade 2 and stage C according to Hardy-Vezina and Wilson. Treatment was surgical, initially by a transsphenoidal approach, in which only a biopsy was possible. The patient was then submitted to an orbital-pterional craniotomy with sub-total resection of the tumor. Complementary treatment was indicated with radiotherapy.     

Management of odontoid fractures using anterior screw fixation: analysis of 15 cases

A retrospective analysis of the results of 15 patients with odontoid fractures type II P and II N, according to Roy-Camille's classification is presented. They were operated on by an anterior approach and direct fixation of the odontoid process through a screw. There were 13 men and 2 women, the age ranging from 14 to 74 years. The follow up period was from 6 to 36 months (mean 20 months). There was only one complication related to the surgical technique: one screw was misplaced and it was necessary another surgery to replace it. There were no deaths in this series. There were no screw breakdown and the fusion rate was 94%. We propose, based on this study, that the classification of Roy-Camille for odontoid fractures should be always used, since it proposes one surgical approach for each type of fracture. The results of this series show that this technique is useful and has advantages over another modalities of treatment. The correct diagnosis of the type of fracture and an appropriate selection of patients are the main elements to achieve good results.     

Giant cavernous angioma: report of two cases

Cavernous angiomas or haemangiomas or yet cavernomas are malformations of the central nervous system classified as occult vascular brain lesions. These rare lesions are clinically silent. They are defined by the presence of abnormally large vascular cavities or sinusoids channels of variable size, with sharp walls, located inside but not invading the brain parenchyma. They can occur at any age, including the neonatal period. Most of the small lesions are located inside the brain parenchyma. No abnormal circulation can be demonstrated in angiography and CT scan can be helpful for diagnosis only in rare occasions. Magnetic resonance is the best exam to demonstrate the lesion. Despite the benign character some lesions may cause neurologic dysfunction when their removal may be difficult. Complete extirpation is the best treatment if the lesion is favorable located and is causing neurological dysfunction. Two cases of giant cavernomas with good outcome after total removal are present. Only three cases of giant cavernomas were reported in the literature.     

Management of cutaneous melanoma M0: state of the art and trends

This article reviews the epidemiology, diagnosis and treatment of cutaneous melanoma, including the most recent developments. The combination of positive family history, fair complexion, number of nevi, exposure to sun and/or chromosomal alterations seem to be implicated in the pathogenesis of cutaneous melanoma. Melanomas can be classified according to their growth patterns, and tumour microstaging is of straightforward predictive value for survival and risk of metastasis, although new factors are also being investigated. As yet, surgical excision is the only effective treatment available for primary tumours, resection margins varying according to tumour thickness. Elective node dissection is, however, no longer advocated for melanomas thinner than 1.5 mm, and there is disagreement as to its role for thicker lesions. In contrast, selective node dissection at the time of definitive surgery is becoming more widely accepted, with regional node dissection being restricted to positive cases. Therapeutic dissection is required for lymph node involvement, the most common pattern of recurrence from melanoma, which affects nearly 30% of all patients. Complete remission rates from isolated limb perfusion, which has been employed in patients with multiple recurrences or in-transit metastases, range from 40 to 90%, depending on drugs and techniques used in different series; the best responses so far have been obtained with tumour necrosis factor in combination with melphalan. Patients with thick lesions (> 4 mm) or lymph node metastases have a high risk of micrometastases that would warrant adjuvant therapy. The only agent found to affect survival is interferon alpha-2.     

Late Gastric Pouch Necrosis after Lap-Band<Superscript>®</Superscript>, Treated by an Individualized Conservative Approach

Late band slippage has occurred in nearly 3-10% of patients after laparoscopic adjustable gastric banding (LAGB) with an average delay of 13 months. Band slippage can rarely lead to necrosis of the enlarged pouch, a potentially life-threatening condition. We report a female (BMI 39.92 with co-morbidities) who developed acute outlet obstruction 2 years after LAGB placement. After prompt band deflation, an urgent Gastrografin swallow showed stomach slippage without emptying. At re-operation pouch strangulation was discovered. The pouch appeared to be ill-fated, but as no tear was evident on intra-operative assessment, we decided to simply remove the band and drain. The patient was successfully discharged after 8 days, and the last upper endoscopy showed only a large ulcer in the fundus that was healing. Proper and prompt management of symptomatic patients with stomach slippage, with early operation when acute obstruction is evident, can enable a successful stomach-sparing approach.