Use of Second Window ICG in spinal cord biopsy of a mildly contrast-enhancing lesion: Technical note and review of the literature.

INTRODUCTION: Indocyanine green (ICG) is commonly used to visualize cerebral vasculature, particularly in the management of cerebral aneurysms. There have also been attempts to use ICG for visualization of tumors. Injection of ICG followed by immediate fluorescence microscopy is limited by the short time window for imaging and administration and restricted depth of imaging. Second Window Indocyanine Green (SWIG) addresses these issues by allowing for longer contrast times and the imaging of deeper regions of brain tissue. Biopsy of spinal cord lesions is often difficult for a variety of reasons, including the delicate nature of the tissue and differentiating normal from lesional tissue visually, especially in lesions with heterogeneous enhancement. METHODS: In this case report, we describe the use of second window ICG to facilitate the visualization of a spinal cord lesion and subsequent biopsy of the lesion. RESULTS: This patient is a 24-year-old female who had recurrence of a suprasellar germinoma. An MRI of the rest of the neuraxis was performed to assess for the presence of drop metastases. The spinal cord from C2-5 was expanded with areas of patchy enhancement; however, this lesion was asymptomatic. The patient's oncologist requested a biopsy of this lesion to help direct subsequent care of her recurrent germinoma. The day before surgery, the patient had an intravenous injection of ICG dye. She then underwent a C3-5 laminectomy for biopsy of her cervical intramedullary lesion. After opening of the dura, no visible abnormality of the spinal cord could be identified. A Stryker endoscope showed an area of ICG uptake in the cord at approximately the C3-4 level. A midline myelotomy was centered over the ICG demarcated area and several samples were taken for pathology. Final biopsy results determined the lesion to be spinal cord parenchyma with perivascular and intraparenchymal lymphocytes - not consistent with spinal cord tumor or germinoma. CONCLUSION: Second Window ICG is effective in visualizing otherwise visually unremarkable spinal cord lesions. This technology can facilitate biopsy of these lesions and possibly their surgical resection.

The role of MRI pelvimetry in predicting technical difficulty and outcomes of open and minimally invasive total mesorectal excision: a systematic review.

BACKGROUND: The difficulty of performing total mesorectal excision (TME) for rectal cancer partly relies on the surgeon's subjective assessment of the individual patient's pelvic anatomy and tumour characteristics, which generally influences the choice of platform used (open, laparoscopic, robotic or trans-anal surgery). Recent studies have found associations between several anatomical pelvic measurements and surgical difficulty. The aim of this study was to systematically review existing data reporting the use of magnetic resonance imaging (MRI)-based pelvic measurements to predict technical difficulty and outcomes of TME, and determine whether pelvimetry could optimise patient-specific selection of a particular surgical approach. METHODS: MEDLINE, Embase and Cochrane Library databases were systematically searched for studies reporting MRI-based pelvic measurements in patients undergoing surgery for rectal cancer, and the effect of these measurements on surgical difficulty. RESULTS: Eleven studies reporting the association between MRI-pelvimetry measurements and rectal cancer surgical outcomes were included. Indicators for surgical difficulty used in the included studies were involved circumferential resection margin, longer operative time, incomplete TME, higher blood loss, anastomotic leak, conversion to open surgery and overall complications. Bony pelvic measurements which were associated with increased surgical difficulty in more than one study were a smaller interspinous distance, a smaller intertubercle distance, a smaller pelvic inlet and larger pubic tubercle height. Two studies identified larger mesorectal fat area as a predictor of surgical difficulty. CONCLUSIONS: Bony pelvic measurements may predict surgical difficulty during TME, however, use of different indicators of difficulty limit comparison between studies. Early data suggest MRI soft tissue measurements may predict surgical difficulty and warrants further investigation.

Is neoadjuvant chemoradiotherapy sufficient in patients with advanced rectal malignancy and positive extra-mesorectal lateral lymph nodes?

AIM: There is current debate about the optimal management of lateral pelvic lymph nodes (LPLNs) in rectal cancer between Western and Eastern centres. This paper aims to report the rate of histologically proven positive LPLNs in a group of patients undergoing the conventional Western approach to primary and recurrent rectal cancer. METHOD: A retrospective cohort review of all patients who underwent LPLN dissection at Royal Prince Alfred Hospital in Sydney, Australia. This included patients who underwent pelvic exenteration who had LPLNs excised either en bloc for laterally invasive or recurrent tumours or as part of selective node dissection for suspicious lymph nodes on preoperative imaging. Histopathological results for these patients were compared with node status at preoperative imaging. RESULTS: Seventy-one patients satisfied the inclusion criteria. Of those patients with positive nodes on histology, 27% (9/33) with radiologically positive LPLNs were treated with preoperative radiotherapy and 75% (9/12) with radiologically positive LPLNs were not treated with preoperative radiotherapy (P = 0.004). None of the 12 patients with radiologically negative nodes treated with radiotherapy had positive nodes; 25% (3/12) of the patients with radiologically negative nodes who were not treated with radiotherapy had positive nodes. Fifty-three per cent of patients developed postoperative complications. CONCLUSION: Our study suggests that in patients with radiologically positive LPLNs chemoradiotherapy may not be enough to sterilize these extra-mesorectal lymph nodes as a large proportion (27%) will have residual viable adenocarcinoma cells. In patients with radiologically negative LPLNs, however, the addition of chemoradiotherapy may serve to adequately sterilize these lymph nodes without the need for prophylactic LPLN dissection.

Interaction between spent fuel components and carbonate rocks.

Deep geological repository is considered the internationally accepted method for spent fuel (SF) disposal. In countries where salt, clay, tuff and granite are unavailable at geologically suitable area, other rock types may come into consideration. In Israel, carbonate rocks make up a significant portion of the surface and subsurface lithologies, thus, low permeability carbonates were evaluated as possible host rocks for a repository, and for an interim storage facility. Sorption and retardation capacity of SF components to low permeability carbonate rocks were evaluated using their chemical simulants. Strontium and Cs represent components that may leach during interim storage, while U and Ce (as a simulant for redox-active actinides) represent components that may leach under repository conditions. Rocks from the Upper Cretaceous Mount Scopus Group were sampled from boreholes at the Yamin Plateau, Israel. Single point batch experiments were conducted with synthetic rainwater spiked with tracers and interacted with five rock types of various particle sizes at 25 °C. Results were evaluated using the LeachXS™-ORCHESTRA geochemical speciation and data management program. Cerium removal was found to be related to the HCO3- concentration in solution, where Ce precipitated as Ce2(CO3)3·XH2O and as an amorphous carbonate phase. Removal of Cs and Sr was controlled by clays. No Sr co-precipitation as carbonate species was observed. Uranium was removed mainly by sorption onto solid organic matter, whereas clays had no significant role in U sorption. Iron-(hydr) oxides may have also played a role in U removal. Calculated partition coefficients for U, Cs, and Sr were in the order of 101-102 mL/g. Grain size had no significant effect on the retention capacity of the studied rocks due to similar effective surface area. The current study indicates that a repository or an interim storage facility within carbonate rocks, would provide only partial isolation of radionuclides from the environment, hence, additional engineered barriers may be required.

Addressing the empty pelvic syndrome following total pelvic exenteration: does mesh reconstruction help?

AIM: Perineal wound complications and pelvic abscesses remain a major source of morbidity after total pelvic exenteration. The void created in the pelvis after these multi-visceral resections leads to fluid accumulation and translocation of bowel within the pelvic cavity, which may increase the risk of pelvic abscess, perineal fluid discharge with perineal wound dehiscence and prolonged ileus. This study describes a novel technique using degradable synthetic mesh with overlying omentum to preclude small bowel and fill the empty space after total pelvic exenteration, and aimed to investigate the rate of pelvic abscess and perineal wound-related complications in this group. METHOD: Ten patients who underwent total pelvic exenteration followed by implantation of degradable synthetic mesh at a quaternary referral centre were identified and included. The mesh was moulded to the contours of the bony pelvis at the level of the pubic symphysis anteriorly and inferior to the sacral promontory posteriorly. The data on the number of postoperative perineal wound-related complications including pelvic abscesses were collected. RESULTS: There was no perioperative mortality. Five patients (50%) developed postoperative complications. One patient developed an abscess inferior to the mesh that required surgical drainage and another had a pre-sacral collection that was successfully managed conservatively. Two patients developed intra-abdominal collections requiring percutaneous drainage. Median length of stay was 20 days (range 16-35). No perineal hernia or entero-perineal fistula was detected in any patient either clinically or radiologically at a median follow-up of 7 months. CONCLUSION: Degradable synthetic mesh reconstruction following exenterative surgery may reduce postoperative complications related to the perineal wound.

Posterior high sacral segmental disconnection prior to anterior en bloc exenteration for recurrent rectal cancer.

This article describes a novel technique for en bloc resection of locally recurrent rectal cancer that invades the high sacral bone (above S3). The involved segment of the sacrum is mobilised with osteotomes during an initial posterior approach before an anterior abdominal phase where the segment of sacral bone is delivered with the specimen. This allows en bloc resection of the involved sacrum while preserving uninvolved distal and contralateral sacral bone and nerve roots. The goal is to obtain a clear bony margin and offer a chance of cure while improving functional outcomes by maintaining pelvic stability and minimising neurological deficit.

Lateral pelvic compartment excision during pelvic exenteration.

BACKGROUND: Involvement of the lateral compartment remains a relative or absolute contraindication to pelvic exenteration in most units. Initial experience with exenteration in the authors' unit produced a 21 per cent clear margin rate (R0), which improved to 53 per cent by adopting a novel technique for en bloc resection of the iliac vessels and other side-wall structures. The objective of this study was to report morbidity and oncological outcomes in consecutive exenterations involving the lateral compartment. METHODS: Patients undergoing pelvic exenteration between 1994 and 2014 were eligible for review. RESULTS: Two hundred consecutive patients who had en bloc resection of the lateral compartment were included. R0 resection was achieved in 66·5 per cent of 197 patients undergoing surgery for cancer and 68·9 per cent of planned curative resections. For patients with colorectal cancer, a clear resection margin was associated with a significant overall survival benefit (P = 0·030). Median overall and disease-free survival in this group was 41 and 27 months respectively. Overall 1-, 3- and 5-year survival rates were 86, 46 and 35 per cent respectively. No predictors of survival were identified on univariable analysis other than margin status and operative intent. Excision of the common or external iliac vessels or sciatic nerve did not confer a survival disadvantage. CONCLUSION: The continuing evolution of radical pelvic exenteration techniques has seen an improvement in R0 margin status from 21 to 66·5 per cent over a 20-year interval by routine adoption of a more lateral anatomical plane. Five-year overall survival rates are comparable with those for more centrally based tumours.

Clinical algorithms for the diagnosis and management of urological leaks following pelvic exenteration.

BACKGROUND: Urine leak following pelvic exenteration for locally advanced pelvic malignancy is a major complication leading to increased mortality, morbidity and length of stay. We reviewed our experience and developed a diagnostic and management algorithm for urine leaks in this patient population. METHODS: Consecutive patients who underwent en bloc cystectomy and conduit formation as part of pelvic exenteration at a single quaternary referral centre from 1995 to 2012 were reviewed. Patients with urine leak were identified. Medical records were reviewed to extract data on diagnosis and management and a suggested clinical algorithm was developed. RESULTS: Of 325 exenterations, there were 102 conduits, of which 15 patients (15%) developed a conduit related urine leak. Most (14/15) patients were symptomatic. Diagnosis was made by drain creatinine studies (12/15) and/or imaging (15/15). Management comprised of conservative management, radiologic urinary diversion, early surgical revision and late surgical revision in 3, 11, 2 and 1 patients respectively. Important lessons from our 17 year experience include a high index of suspicion in a patient who is persistently septic despite appropriate treatment, the importance of regular drain creatinine studies, CT (computer tomography) with delayed images (CT intravenous pyelogram) when performing a CT for investigation of sepsis and early aggressive management with radiologic urinary diversion to facilitate early healing. CONCLUSION: Urine leak after pelvic exenteration is a complex problem. Conservative management usually fails and early diagnosis and intervention is the key. It is hoped that our algorithms will facilitate diagnosis and subsequent management of this group of patients.

Warm tropical sea surface temperatures in the Late Cretaceous and Eocene epochs.

Climate models with increased levels of carbon dioxide predict that global warming causes heating in the tropics, but investigations of ancient climates based on palaeodata have generally indicated cool tropical temperatures during supposed greenhouse episodes. For example, in the Late Cretaceous and Eocene epochs there is abundant geological evidence for warm, mostly ice-free poles, but tropical sea surface temperatures are generally estimated to be only 15-23 degrees C, based on oxygen isotope palaeothermometry of surface-dwelling planktonic foraminifer shells. Here we question the validity of most such data on the grounds of poor preservation and diagenetic alteration. We present new data from exceptionally well preserved foraminifer shells extracted from impermeable clay-rich sediments, which indicate that for the intervals studied, tropical sea surface temperatures were at least 28-32 degrees C. These warm temperatures are more in line with our understanding of the geographical distributions of temperature-sensitive fossil organisms and the results of climate models with increased CO2 levels.

In vivo ultrasonic measurement of tissue vibration at a stenosis: a case study.

It is known that bruits often can be heard downstream from stenoses. They are thought to be produced by disturbed blood flow and vessel wall vibrations. Our understanding of bruits has been limited, though, to analysis of sounds heard at the level of the skin. For direct measurements from the stenosis site, we developed an ultrasonic pulse-echo multigate system using quadrature phase demodulation. The system simultaneously measures tissue displacements and blood velocities at multiple depths. This paper presents a case study of a severe stenosis in a human infrainguinal vein bypass graft. During systole, nearly sinusoidal vessel wall vibrations were detected. Solid tissue vibration amplitudes measured up to 2 microm, with temporal durations of 100 ms and frequencies of roughly 145 Hz and its harmonics. Cross-axial oscillations were also found in the lumen that correlate with the wall vibrations, suggesting coupling between wall vibration and blood velocity oscillation.

Lung cancer and environmental tobacco smoke: occupational risk to nonsmokers.

The principal epidemiologic evidence that environmental tobacco smoke (ETS) increases the risk of lung cancer in (lifelong) nonsmokers is from studies of nonsmoking women married to smokers. This article estimates exposure-response curves for 14 studies (1, 249+ cases, 7 countries) with data on lung cancer categorized by the number of cigarettes/day smoked by the husband. The pooled results from the five U.S. studies alone are extrapolated to ETS levels in the workplace using measures of serum cotinine and nicotine samples from personal monitors as markers of exposure to ETS. It is predicted that the increase in lung cancer risk for nonsmoking women from average ETS exposure at work (among those exposed at work) is on the order of 25% (95% confidence interval (CI) = 8, 41) relative to background risk (i.e., with no ETS exposure from any source). This compares to an estimate of 39% (95% CI = 5, 65) for nonsmoking women whose husbands smoke at the adult male smoker's average of 25 cigarettes/day. At the 95th percentiles of exposure, the estimate from spousal smoking is 85% (95% CI = 32, 156), compared to 91% (95% CI = 34, 167) from workplace ETS exposure. Subject to the validity of the assumptions required in this approach, the outcome supports the conclusion that there is a significant excess risk from occupational exposure to ETS. The excess risk from ETS at work is typically lower than that from spousal smoking, but may be higher at the 95th percentiles of exposure.

The effect of queuosine on tRNA structure and function.

Computational modeling was performed to determine the potential function of the queuosine modification of tRNA found in wobble position 34 of tRNAasp, tRNAasn, tRNAhis, and tRNAtyr. Using the crystal structure of tRNAasp and a tRNA-tRNA-mRNA complex model, we show that the queuosine modification serves as a structurally restrictive base for tRNA anticodon loop flexibility. An extended intraresidue and intramolecular hydrogen bonding network is established by queuosine. The quaternary amine of the 7-aminomethyl side chain hydrogen bonds with the base's carbonyl oxygen. This positions the dihydroxycyclopentenediol ring of queuosine in proper orientation for hydrogen bonding with the backbone of the neighboring uridine 33 residue. The interresidue association stabilizes the formation of a cross-loop hydrogen bond between the uridine 33 base and the phosphoribosyl backbone of the cytosine at position 36. Additional interactions between RNAs in the translation complex were studied with regard to potential codon context and codon bias effects. Neither steric nor electrostatic interaction occurs between aminoacyl- and peptidyl-site tRNA anticodon loops that are modified with queuosine. However, there is a difference in the strength of anticodon/codon associations (codon bias) based on the presence or lack of queuosine in the wobble position of the tRNA. Unmodified (guanosine-containing) tRNAasp forms a very stable association with cytosine (GAC), but is much less stable in complex with a uridine-containing codon (GAU). Queuosine-modified tRNAasp exhibits no bias for either of cognate codons GAC or GAU and demonstrates a lower binding energy similar to the wobble pairing of guanosine-containing tRNA with a GAU codon. This is proposed to be due to the inflexibility of the queuosine-modified anticodon loop to accommodate proper positioning for optimal Watson-Crick type associations. A preliminary survey of codon usage patterns in oncodevelopmental versus housekeeping gene transcripts suggests a significant difference in bias for the queuosine-associated codons. Therefore, the queuosine modification may have the potential to influence cellular growth and differentiation by codon bias-based regulation of protein synthesis for discrete mRNA transcripts.

Inorganic arsenic: a need and an opportunity to improve risk assessment.

This paper presents views on the current status of (inorganic) arsenic risk assessment in the United States and recommends research needed to set standards for drinking water. The opinions are those of the Arsenic Task Force of the Society for Environmental Geochemistry and Health, which has met periodically since 1991 to study issues related to arsenic risk assessment and has held workshops and international conferences on arsenic. The topic of this paper is made timely by current scientific interest in exposure to and adverse health effects of arsenic in the United States and passage of the Safe Drinking Water Act Amendment of 1996, which has provisions for a research program on arsenic and a schedule mandating the EPA to revise the maximum contaminant level of arsenic in drinking water by the year 2001. Our central premise and recommendations are straightforward: the risk of adverse health effects associated with arsenic in drinking water is unknown for low arsenic concentrations found in the United States, such as at the current interim maximum contaminant level of 50 microg/l and below. Arsenic-related research should be directed at answering that question. New epidemiological studies are needed to provide data for reliable dose-response assessments of arsenic and for skin cancer, bladder cancer, or other endpoints to be used by the EPA for regulation. Further toxicological research, along with the observational data from epidemiology, is needed to determine if the dose-response relationship at low levels is more consistent with the current assumption of low-dose linearity or the existence of a practical threshold. Other recommendations include adding foodborne arsenic to the calculation of total arsenic intake, calculation of total arsenic intake, and encouraging cooperative research within the United States and between the United States and affected countries.

Skin cancer and inorganic arsenic: uncertainty-status of risk.

The current U.S. EPA standard for inorganic arsenic in drinking water is 50 ppb (microgram/L), dating to the National Interim Primary Drinking Water Regulation of 1976. The current EPA risk analysis predicts an increased lifetime skin cancer risk on the order of 3 or 4 per 1000 from chronic exposure at that concentration. Revision of the standard to only a few ppb, perhaps even less than 1 ppb, may be indicated by the EPA analysis to reduce the lifetime risk to an acceptable level. The cost to water utilities, and ultimately to their consumers, to conform to such a large reduction in the standard could easily reach several billion dollars, so it is particularly important to assess accurately the current risk and the risk reduction that would be achieved by a lower standard. This article addresses the major sources of uncertainty in the EPA analysis with respect to this objective. Specifically, it focuses on uncertainty and variability in the exposure estimates for the landmark study of Tseng and colleagues in Taiwan, analyzed using a reconstruction of the their exposure data. It is concluded that while the available dataset is suitable to establish the hazard of skin cancer, it is too highly summarized for reliable dose-response assessment. A new epidemiologic study is needed, designed for the requirements of dose-response assessment.

Gene disruptions indicate an essential function for the LmmCRK1 cdc2-related kinase of Leishmania mexicana.

The generation of homozygous null mutants for the crk1 Cdc2-Related Kinase of Leishmania mexicana was attempted using targeted gene disruption. Promastigote mutants heterozygous for crk1 were readily isolated with a hyg-targeting fragment, but attempts to create null mutants by second-round transfections with a bie-targeting fragment yielded two classes of mutant, neither of which was null. First, the transfected fragment formed an episome; second, the cloned transfectants were found to contain wild-type crk1 alleles as well as hyg and ble integrations. DNA-content analysis revealed that these mutants were triploid or tetraploid. Plasticity in chromosome number following targeting has been proposed as a means by which Leishmania avoids deletion of essential genes. These data support this theory and implicate crk1 as an essential gene, validating CRK1 as a potential drug target. L mexicana transfected with a Trypanosoma brucel homologue, tbcrk1, was shown to be viable in an immcrk1 null background, thus showing complementation of function between these trypanosomatid genes. The expression of crk1 was further manipulated by engineering a six-histidine tag at the C-terminus of the kinase, allowing purification of the active complex by affinity selection on Nl(2+)-nitriloacetic acid (NTA) agarose.