MALDI imaging–based identification of prognostically relevant signals in bladder cancer using large-scale tissue microarrays

ObjectiveAlthough most patients with urinary bladder cancer present with noninvasive and low-malignant stages of the disease, about 20% eventually develop life-threatening metastatic tumors. This study was designed to evaluate the potential of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify molecular markers predicting the clinical course of bladder cancer.Materials and methodsWe employed MALDI-MSI to a bladder cancer tissue microarray including paraffin-embedded tissue samples from 697 patients with clinical follow-up data to search for prognostically relevant associations.ResultsAnalysis of our MALDI imaging data revealed 40 signals in the mass spectra (m/z signals) associated with epithelial structures. The presence of numerous m/z signals was statistically related to one or several phenotypical findings including tumor aggressiveness (stage, grade, or nodal status; 30 signals), solid (5 signals) or papillary (3 signals) growth patterns, and increased (6 signals) or decreased (12 signals) cell proliferation, as determined by Ki-67 immunohistochemistry. Two signals were linked with tumor recurrence in noninvasive (pTa category) tumors, of which one was also related to progression from pTa-category to pT1-category disease. The absence of one m/z signal was linked with decreased survival in the subset of 102 muscle-invasive cancers.ConclusionOur data demonstrate the suitability of combining MSI and large-scale tissue microarrays to simultaneously identify and validate clinically useful molecular markers in urinary bladder cancer.     

Extended endoscopic endonasal transclival approach to the ventrolateral brainstem and related cisternal spaces: anatomical study

Advances in endoscopic endonasal skull base surgery have led to the development of new routes to areas beyond the midline skull base. Recently, feasible surgical corridors to the lateral skull base have been described. The aim of this study was to describe the anatomical exposure of the ventrolateral brainstem and posterior fossa through an extended endoscopic endonasal transclival transpetrosal and transcondylar approach. Six human heads were used for the dissection process. The arterial and venous systems were injected with red- and blue-colored latex, respectively. A pre- and postoperative computed tomography (CT) scan was carried out on every head. The endoscopic endonasal transclival approach was extended through an anterior petrosectomy and a medial condylectomy. A three-dimensional model of the approach was reconstructed, using a dedicated software, from the overlapping of the pre- and post-dissection CT imaging of the specimen. An extended endoscopic transclival approach allows to gain access through an extradural anterior petrosectomy and medial condylectomy to the anterolateral surface of the brainstem and the posterior fossa. Two main intradural anatomical corridors can be described: first, between the V cranial nerve in the prepontine cistern and the VII–VIII cranial nerves in the cerebellopontine and cerebellomedullary cistern; second, between the VII–VIII cranial nerves and the IX cranial nerve, in the premedullary cistern. Extending the transclival endoscopic approach by performing an extradural anterior petrosectomy and a medial condylectomy provides a safe and wide exposure of the anterolateral brainstem with feasible surgical corridors around the main neurovascular structures.     

Clinical evaluation of hyponatremia and hypovolemia in critically ill adult neurologic patients: contribution of the use of cumulative balance of sodium

Purpose

Knowledge of the cumulative balance of sodium (CBS) is important for the diagnosis of salt disorders and water homeostasis and has the potential to predict hypovolemic status in acute neurological patients. However, an extensive application of the use of CBS is still lacking in the intensive care setting, where salt and water homeostasis represents a priority.

Methods

Records of consecutive series of acute neurological patients admitted to a neurointensive care unit over a 6-month period were retrospectively reviewed. CBS was calculated at the admission to the Emergency Department. Discrimination between cerebral salt-wasting syndrome (CSWS) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was performed on the basis of the classical criteria. Additionally, we used the findings of a negative CBS exceeding 2 mEq/kg for the diagnosis of CSWS. Two independent clinicians who were blinded to the CBS results performed diagnosis of the causes of hyponatremia and estimated the daily volemic status of the patients on the basis of clinical parameters. Logistic regression analysis was used to determine the independent prognostic factors of hypovolemia.

Results

Thirty-five patients were studied for a total of 418 days. Four patients (11.4 %) fitted the criteria of CSWS and three patients (8.5 %) had SIADH. The unavailability of the CBS led to a wrong diagnosis in three of the eight hyponatremic patients (37.5 %). The risk of developing hypovolemia in patients with negative CBS was 7.1 times higher (CI 3.86–13.06; p < 0.001). Multivariate analysis revealed that negative cumulative fluid balance, negative CBS >2 mEq/kg, and CVP ≤5 cmH₂O were independent prognostic factors for hypovolemia.

Conclusions

CBS is likely to be a useful parameter in the diagnosis of CSWS and a surrogate parameter for estimating hypovolemia in acute neurological patients.     

Risk Factors for Graft Loss Due to Acute Vascular Complications in Adult Renal Transplantation Using Grafts Without Vascular Anomalies

BackgroundVascular complications are the main cause of early graft loss in renal transplant (RT). A graft with multiple vessels represents the most validated risk factor. The aim of the present study was to identify potential predictive factors for acute vascular complications causing graft loss when graft vascular anomalies are excluded.MethodsThis is a retrospective case-control (1:3 ratio) study extrapolated from the RT series of the Renal Transplant Unit - Udine University Hospital, during the period 1993-2017. Grafts with multiple vessels and retransplant cases were excluded.ResultsThe overall prevalence of graft loss due to acute vascular complications was 2.6% (25/961). Seventeen complicated recipients had grafts without vascular anomalies (case group). The median time between RT and complication was 6 days (interquartile range, 4-23 days). The following types of vascular complications were recorded: 5 isolated renal artery thromboses (0.5%), 4 isolated renal vein thromboses (0.4%), 4 combined renal artery and vein thromboses (0.3%), 3 renal artery ruptures due to mycotic arteritis (0.3%), and 1 renal artery nonmycotic pseudoaneurysm (0.1%). No differences were recorded between the groups in terms of donors and grafts characteristics. Complicated recipients showed a statistically higher prevalence of thromboembolism history (P = .046) and vascular atherosclerosis (P = .048). During the postoperative course, blood stream infections (P = .02), acute rejection (P = .03), bleeding from a nonmacrovascular source (P = .04), and multiple reintervention because of nonvascular complications (P = .03) were identified as significant risk factors.ConclusionsRecipient characteristics and post-RT complications rather than donor and graft characteristics are relevant risk factors for graft loss due to acute vascular complications when graft vascular anomalies are excluded.     

Laparoscopic gastrointestinal anastomoses using knotless barbed sutures are safe and reproducible: a single-center experience with 201 patients

Background

Intestinal anastomosis is a complex procedure during laparoscopy, mainly due to the difficulties knotting the sutures. Unidirectional barbed sutures have been proposed to simplify wall and mesentery closure, but the results for intestinal anastomosis are not clear. This study aimed to establish the feasibility and the safety of laparoscopic intestinal anastomosis using barbed suture.

Methods

Between June 2011 and May 2012, 15-cm-long unidirectional absorbable barbed sutures (V-Loc; Covidien, Mansfield, MA, USA) were used for all laparoscopic intestinal anastomoses: one suture for closure of intestinal openings after mechanical anastomoses and two sutures for hand-sewn anastomoses.

Results

Over a 1-year period, 201 consecutive patients required 220 laparoscopic anastomoses for gastrojejunostomy (n = 177; 172 during Roux-en-Y gastric bypass and 5 after gastrectomy), ileocolostomy (n = 15), colocolostomy (n = 1), esophagojejunostomy (n = 5), and jejunojejunostomy (n = 22; 4 after small bowel resection and 18 during gastric bypass or gastrectomy). Senior and training surgeons performed 209 closures of intestinal openings and 11 hand-sewn anastomoses. There was no conversion to usual sutures. One fistula occurred in an esophagojejunostomy and was managed conservatively. One self-limited anastomotic bleeding occurred, and no anastomotic stenosis occurred during 6 months of follow-up evaluation.

Conclusions

The use of knotless barbed suture for laparoscopic intestinal anastomosis is safe and reproducible.     

Giant cell tumor and Paget's disease of bone in one family: geographic clustering

Giant cell tumor is a rare complication of Paget's disease of bone. Typically, this tumor occurs in the case of polyostotic disease and only in pagetic bones. This tumor rarely has been seen in multiple family members who have Paget's disease, although Paget's bone disease clearly has a hereditary component. Our report documents four cases of polyostotic Paget's bone disease complicated by benign giant cell tumor. In two patients, the giant cell tumor also was multifocal. All patients were from one family. They were born in Avellino and reside in Campania, a Southern Italian region. The ancestors of the patients with familial giant cell tumor in Paget's bone disease were born in the same geographic area. These data suggest that a combination of environmental and genetic factors could be responsible for linkage of the patients born in Avellino with this neoplasm that is highly unusual in patients with Paget's disease of bone.     

Lipoprotein(a)-associated atherothrombotic risk in hemodialysis patients

BACKGROUND: Hemodialysis patients show a considerably higher risk of atherothrombotic disease than the general population. We investigated both lipoprotein(a) [Lp(a)] plasma levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of atherothrombotic events in hemodialysis patients compared with subjects showing a normal kidney function. Methods: Lp(a) levels and apo(a) isoforms were determined in 118 hemodialysis patients, including 59 with prior atherothrombotic events, and in 182 subjects with normal creatinine clearance, including 82 who experienced a prior atherothrombotic event. Results: Lp(a) levels in hemodialysis patients (median; 20 mg/dl) were higher (p < 0.01) than in age- and sex-matched subjects with normal renal function without a history of atherothrombosis (11.3 mg/dl). Among hemodialysis patients, median Lp(a) levels were higher in subjects with than in those without prior atherothrombosis (34 vs. 15 mg/dl, p < 0.05). In hemodialysis patients and in subjects without nephropathy, the percentage of low-molecular-weight apo(a) phenotypes were significantly higher in patients with than in those without a history of prior atherothrombotic events (56.9% vs. 33.9%, p < 0.05; 62.2% vs. 25%, p < 0.00001,respectively). Stepwise regression analysis indicated that the presence of at least one apo(a) isoform of low molecular weight was an independent predictor of atherothrombosis in hemodialysis patients (p < 0.05). Conclusions: Elevated Lp(a) plasma levels appear to be associated with atherothrombosis, independent of their origin due to genetic factors or related to the impaired kidney function. Low-molecular-weight apo(a) isoforms are reliable genetic markers of atherothrombosis both in patients with impaired kidney function and in subjects without nephropathy.     

Neurostimulation systems for deep brain stimulation: in vitro evaluation of magnetic resonance imaging-related heating at 1.5 tesla

PURPOSE: To assess magnetic resonance imaging (MRI)-related heating for a neurostimulation system (Activa Tremor Control System, Medtronic, Minneapolis, MN) used for chronic deep brain stimulation (DBS). MATERIALS AND METHODS: Different configurations were evaluated for bilateral neurostimulators (Soletra Model 7426), extensions, and leads to assess worst-case and clinically relevant positioning scenarios. In vitro testing was performed using a 1.5-T/64-MHz MR system and a gel-filled phantom designed to approximate the head and upper torso of a human subject. MRI was conducted using the transmit/receive body and transmit/receive head radio frequency (RF) coils. Various levels of RF energy were applied with the transmit/receive body (whole-body averaged specific absorption rate (SAR); range, 0.98-3.90 W/kg) and transmit/receive head (whole-body averaged SAR; range, 0.07-0.24 W/kg) coils. A fluoroptic thermometry system was used to record temperatures at multiple locations before (1 minute) and during (15 minutes) MRI. RESULTS: Using the body RF coil, the highest temperature changes ranged from 2.5 degrees-25.3 degrees C. Using the head RF coil, the highest temperature changes ranged from 2.3 degrees-7.1 degrees C.Thus, these findings indicated that substantial heating occurs under certain conditions, while others produce relatively minor, physiologically inconsequential temperature increases. CONCLUSION: The temperature increases were dependent on the type of RF coil, level of SAR used, and how the lead wires were positioned. Notably, the use of clinically relevant positioning techniques for the neurostimulation system and low SARs commonly used for imaging the brain generated little heating. Based on this information, MR safety guidelines are provided. These observations are restricted to the tested neurostimulation system.     

Intraoperative DTI and brain mapping for surgery of neoplasm of the motor cortex and the corticospinal tract: our protocol and series in BrainSUITE

We report our preliminary series of patients treated for lesions involving the motor cortex and the corticospinal tract in BrainSuite, with intraoperative MRI, tractography and "neuronavigated" electrophysiological cortical and subcortical mapping. An exact localization of the cortical and subcortical functional areas is mandatory for executing surgery of intra-parenchymal neoplasm involving the motor cortex and the corticospinal tract. Nowadays modern technology offers a variety of tools to reduce as much as possible postoperative deficits during surgery of cerebral eloquent areas. From December 2008 and June 2010, 18 patients underwent functional surgery, for neoplasm involving the motor cortex and/or the subcortical pathway, in BrainSuite. Our preliminary series include 14 gliomas and 4 metastases; Table 1 summarizes all of the data. We included in this series patients with complete removal of lesions of eloquent areas with an average distance from the corticospinal tract of 4 mm. Six neoplasms were considered in contact and/or involving the motor cortex, while in 18 cases (100%) the tumour involved eloquent areas concerning the corticospinal tract. All of the patients underwent complete removal of the lesion as subsequently demonstrated by intraoperative postsurgical MRI. Our series highlights the good integration and the high compatibility between BrainSUITE with 1.5 T intraoperative magnetic field and neurophysiological monitoring. We strongly believe that intraoperative MRI with DTI allows us to treat complex surgery tumours that without its auxilium we would not be able to deal with.     

Complete Pathologic Response after Combined Modality Treatment for Rectal Cancer and Long-Term Survival: A Meta-Analysis

Background

Complete pathologic response (CPR) after neoadjuvant chemoradiotherapy (combined modality treatment, CMT) for rectal cancer seems associated with improved survival compared to partial or no response (NPR). However, previous reports have been limited by small sample size and single-institution design.

Methods

A systematic literature review was conducted to detect studies comparing long-term results of patients with CPR and NPR after CMT for rectal cancer. Variables were pooled only if evaluated by 3 or more studies. Study end points included rates of CPR, local recurrence (LR), distant recurrence (DR), 5-year overall survival (OS), and disease-free survival (DFS).

Results

Twelve studies (1,913 patients) with rectal cancer treated with CMT were included. CPR was observed in 300 patients (15.6%). CPR and NPR patient groups were similar with respect to age, sex, tumor size, distance of tumor from the anus, and stage of disease before treatment. Median follow-up ranged from 23 to 46?months. CPR patients had lower rates of LR [0.7% vs. 2.6%; odds ratio (OR) 0.45, 95% confidence interval (CI) 0.22?C0.90, P?=?0.03], DR (5.3% vs. 24.1%; OR 0.15, 95% CI 0.07?C0.31, P?=?0.0001), and simultaneous LR?+?DR (0.7% vs. 4.8%; OR 0.32, 95% CI 0.13?C0.79, P?=?0.01). OS was 92.9% for CPR versus 73.4% for NPR (OR 3.6, 95% CI 1.84?C7.22, P?=?0.002), and DFS was 86.9% versus 63.9% (OR 3.53, 95% CI 1.62?C7.72, P?=?0.002).

Conclusions

CPR after CMT for rectal cancer is associated with improved local and distal control as well as better OS and DFS.