Robotic transanal minimally invasive surgery - technical, oncological and patient outcomes from a single institution.

AIM: Robotic transanal minimally invasive surgery (R-TAMIS) is gaining traction around the globe as an alternative to laparoscopic conventional TAMIS for local excision of benign and early malignant rectal lesions. The aim was to analyse patient and oncological outcomes of R-TAMIS for consecutive cases in a single centre. METHODS: A prospective analysis of consecutive R-TAMIS procedures over a 12-month period was performed. Data were collated from hospital databases and theatre registers. RESULTS: Eleven patients (six men, five women), mean age 69.81 years (51-92 years), underwent R-TAMIS over 12 months utilizing a da Vinci Xi platform. The mean lesion size was 36 mm (20-60 mm) with a mean distance from the anal verge of 7.5 cm (3-14 cm). Five lesions were posterior in anatomical location, four anterior, one right lateral and one left lateral. All procedures were performed in the lithotomy position using a GelPOINT Path Platform. Mean operative time was 64 min (40-100 min). Complete resection was achieved in 10/11 patients with two patients being upgraded to a diagnosis of adenocarcinoma. Nine patients were diagnosed with dysplastic lesions. Four patients had a false positive diagnosis of an invasive tumour on MRI. Six patients required suturing for full-thickness resections. One patient had a postoperative bleed requiring repeat endoscopy and clipping. One patient (full-thickness resection of T3 tumour) proceeded to a formal resection without difficulty with no residual disease (T0N0, 0/22). One patient with a fully resected T2 tumour is undergoing a surveillance protocol. The mean length of stay was 1 day with two patients having a length of stay of 2 days and one patient of 4 days. CONCLUSION: R-TAMIS could potentially represent a safe novel approach for local resection of rectal lesions.

An atypical genotype of Toxoplasma gondii as a cause of mortality in Hector's dolphins (Cephalorhynchus hectori).

Hector's dolphins (Cephalorhynchus hectori) are a small endangered coastal species that are endemic to New Zealand. Anthropogenic factors, particularly accidental capture in fishing nets, are believed to be the biggest threat to survival of this species. The role of infectious disease as a cause of mortality has not previously been well investigated. This study investigates Toxoplasma gondii infection in Hector's dolphins, finding that 7 of 28 (25%) dolphins examined died due to disseminated toxoplasmosis, including 2 of 3 Maui's dolphins, a critically endangered sub-species. A further 10 dolphins had one or more tissues that were positive for the presence of T. gondii DNA using PCR. Genotyping revealed that 7 of 8 successfully amplified isolates were an atypical Type II genotype. Fatal cases had necrotising and haemorrhagic lesions in the lung (n=7), lymph nodes (n=6), liver (n=4) and adrenals (n=3). Tachyzoites and tissue cysts were present in other organs including the brain (n=5), heart (n=1), stomach (n=1) and uterus (n=1) with minimal associated inflammatory response. One dolphin had a marked suppurative metritis in the presence of numerous intra-epithelial tachyzoites. No dolphins had underlying morbillivirus infection. This study provides the first evidence that infectious agents could be important in the population decline of this species, and highlights the need for further research into the route of entry of T. gondii organisms into the marine environment worldwide.

Three- and four-dimensional reconstruction of intra-cardiac anatomy from two-dimensional magnetic resonance images.

The present study was designed to evaluate the feasibility and clinical usefulness of three-dimensional (3D) reconstruction of intra-cardiac anatomy from a series of two-dimensional (2D) MR images using commercially available software. Sixteen patients (eight with structurally normal hearts but due to have catheter radio-frequency ablation of atrial tachyarrhythmias and eight with atrial septal defects (ASD) due for trans-catheter closure) and two volunteers were imaged at 1T. For each patient, a series of ECG-triggered images (5 mm thick slices, 2-3 mm apart) were acquired during breath holding. Depending on image quality, T1- or T2-weighted spin-echo images or gradient-echo cine images were used. The 3D reconstruction was performed off-line: the blood pools within cardiac chambers and great vessels were semi-automatically segmented, their outer surface was extracted using a marching cube algorithm and rendered. Intra- and inter-observer variability, effect of breath-hold position and differences between pulse sequences were assessed by imaging a volunteer. The 3D reconstructions were assessed by three cardiologists and compared with the 2D MR images and with 2D and 3D trans-esophagal and intra-cardiac echocardiography obtained during interventions. In every case, an anatomically detailed 3D volume was obtained. In the two patients where a 3 mm interval between slices was used, the resolution was not as good but it was still possible to visualize all the major anatomical structures. Spin-echo images lead to reconstructions more detailed than those obtained from gradient-echo images. However, gradient-echo images are easier to segment due to their greater contrast. Furthermore, because images were acquired at least at ten points in the cardiac cycles for every slice it was possible to reconstruct a cine loop and, for example, to visualize the evolution of the size and margins of the ASD during the cardiac cycle. 3D reconstruction proved to be an effective way to assess the relationship between the different parts of the cardiac anatomy. The technique was useful in planning interventions in these patients.

Simultaneous flow cytometric measurement of K-562 megakaryocytic differentiation and CD56+ large granular lymphocyte cytotoxicity.

K-562 cells have the capacity to undergo multi-lineage differentiation, which may be crucial to their ability to serve as target reservoirs for CD56+ large granular lymphocytes (LGL). Conventional techniques using chromium release assays to measure lymphocyte-mediated cytotoxicity suffer from disadvantages, including radioactive contamination and the inability to simultaneously determine K-562 and/or CD56+ lymphocyte phenotypes. We illustrate here a three-color flow cytometric method providing for the simultaneous evaluation of K-562-CD56+ LGL binding, K-562 cell viability, and the status of K-562 cell differentiation. Phorbol 12-myristate 13-acetate (PMA) engenders megakaryocytic differentiation in K-562 cell populations, as measured by presentation of the beta(3) integrin (gpIIIa, CD61), while maintaining a negative expression of MHC-I and MHC-II molecules. Using the auto-fluorescence of K-562 cells, flow cytometry can be used to demonstrate a significant decrease in CD56+ LGL activity against K-562 cells in populations pre-incubated with PMA. The capacity of three-color flow cytometry to measure lymphocyte-target cell binding and cell death kinetics, while simultaneously determining target cell phenotype, permits the specific localization of CD61-expressing K-562 cells to areas inconsistent with CD56+ LGL-mediated patterns of lysis.

PMA-treated K-562 leukemia cells mediate a TH2-specific expansion of CD4+ T cells in vitro.

Highly enriched preparations of human CD3+CD4+ T-lymphocytes were stimulated with mitogen or OKT3 to determine the capacity of K-562 cells to function as accessory cells. Phorbol 12-myristate 13-acetate (PMA)-treated K-562 cells were induced to differentiate along the megakaryocytic lineage and could supplant monocyte-accessory cell function. Intracytoplasmic analysis of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) established that IL-4, and not IFN-gamma, was preferentially produced by the activated lymphocytes. This polarized stimulation is compatible with a type 2 or humoral immune response of purified T cells co-cultured with differentiated K-562 cells in vitro, and may have implications in immunoregulation due to disease progression.

Evaluation of myocardial perfusion using positron emission tomography in infants following a neonatal arterial switch operation.

This study was performed to examine the use of positron emission tomography (PET) as a method of evaluating myocardial perfusion after the arterial switch operation for correction of transposition of the great arteries. Eleven asymptomatic patients (median age 2.3 years, range 1.3-4.3 years) post successful neonatal arterial switch repair for transposition underwent cardiac PET scanning using N(13) ammonia before and after dipyridamole infusion. Reconstructed data from static scans were analyzed for regional perfusion defects before and after pharmacological stress. Simultaneous assessment of coronary flow before and after stress was performed using a Patlak graphical analysis of data from dynamic scans. Results obtained from PET scanning were correlated with patterns of coronary artery anatomy, electrocardiogram (ECG) recordings, and echocardiographic evaluation. PET scanning demonstrated normal distribution of myocardial perfusion before and after stress in all but one patient, who was found to have a discrete inferior transmural perfusion defect. The defect was well correlated with perioperative ECG changes and a complicated postoperative course. Myocardial blood flow before dipyridamole (0.690 ml/min/g) was similar to reported adult rest values. There was a small but significant (p < 0.002) increase in myocardial blood flow after dipyridamole stress with a mean coronary flow reserve of 1.19 (+/-0.103). Echocardiographic evaluation failed to demonstrate significant wall motion abnormalities in any of the patients. Cardiac PET scanning is a reliable noninvasive method for evaluation of myocardial perfusion in small children. In this study, the incidence of myocardial perfusion defects after the arterial switch operation is lower than previously reported. The data obtained concerning coronary flow and coronary flow reserve after the arterial switch need to be interpreted with caution because normal data in children are not available.

The effects of intensity on the energetics of brief locomotor activity.

The energetic costs associated with locomotion are often estimated only from the energy expended during activity and do not include the costs incurred during recovery. For some types of locomotion, this method overlooks important aspects of the metabolic costs incurred as a result of the activity. These estimates for energetic cost have also been predicted from long-duration, low-intensity activities that do not necessarily reflect all the behavior patterns utilized by animals in nature. We have investigated the effects of different activity intensities on the metabolic expenditure (per unit distance traveled) associated with brief exercise, and offer a more inclusive analysis of how the energetics of short-duration activities might be analyzed to estimate the costs to the animal. Mice ran on a treadmill for 15 or 60 s at 25 %, 50 % or 100 % of maximum aerobic speed (MAS) while enclosed in an open-flow respirometry system. Following the run, each mouse was allowed to recover while remaining enclosed in the respirometry chamber. Excess exercise oxygen consumption (EEOC), the excess volume of oxygen consumed during the exercise period, increased with the duration and increased linearly with the intensity of exercise. In contrast, the volume of oxygen consumed during the recovery period, or excess post-exercise oxygen consumption (EPOC), was independent of exercise intensity and duration and accounted for more than 90 % of the total metabolic cost. The net cost of activity (C(act)), calculated by summing EEOC and EPOC and then dividing by the distance run, increased as both activity duration and intensity decreased. The values for C(act) ranged from 553 ml O(2 )g(-)(1 )km(-)(1) for a 15 s run at 25 % MAS to 43 ml O(2 )g(-)(1 )km(-)(1) for a 60 s run at 100 % MAS. Combining these data with data from a companion paper, we conclude (1) that EPOC is independent of both the duration and intensity of activity when exercise duration is brief in mice, (2) that EPOC accounts for a majority of the oxygen consumed as a result of the activity when exercise durations are short, and (3) that animals can minimize their energy expenditure per unit distance by running faster for a longer period.

Effects of modified and classic Blalock-Taussig shunts on the pulmonary arterial tree.

BACKGROUND: The aim of this study was to assess by angiography the late effects of both classic and modified Blalock-Taussig shunts in terms of growth and development of stenosis and distortion. METHODS: At a mean of 51 months postoperatively, we retrospectively reviewed the results in 78 patients who underwent creation of Blalock-Taussig shunts (25 classic and 71 modified). RESULTS: At the level of the anastomosis, the shunt caused a reduction in diameter of the pulmonary artery in 49% of all shunts, major stenosis (>50% narrowing of the lumen) in 14%, and distortion of the pulmonary artery in 19%, findings that did not correlate with the type of shunt. Distortion did correlate with younger age at the time of shunt operation (p=0.01). CONCLUSIONS: After a Blalock-Taussig shunt, growth of the pulmonary arteries occurred but did not exceed the normal growth of the pulmonary arterial tree. Moreover, a shunt procedure can cause distortion and stenosis of the pulmonary artery, which may have important implications for future corrective surgical intervention. All these findings support earlier complete surgical repair of correctable congenital cardiac defects.

Growth of the right ventricle after successful transcatheter pulmonary valvotomy in neonates and infants with pulmonary atresia and intact ventricular septum.

OBJECTIVES: Since 1990, transcatheter pulmonary valvotomy has become an alternative to surgical valvotomy in the management of neonates and infants with pulmonary atresia and intact ventricular septum. We sought to determine whether right ventricular growth after transcatheter pulmonary valvotomy is commensurate with body growth. METHODS: Laser or radiofrequency-assisted balloon valvotomy was attempted in 12 neonates and infants with pulmonary atresia and intact ventricular septum. Tricuspid and mitral valve dimensions were measured retrospectively on the cross-sectional echocardiograms performed before the procedure and during follow-up. Z-values were used to standardize tricuspid valve dimensions with body size. RESULTS: The atretic pulmonary valve was successfully perforated and dilated in nine of 12 patients. Five of these nine patients required additional transcatheter or surgical procedures to augment the pulmonary blood flow. Of six survivors, five are regularly followed up with a median follow-up of 60 months (range 37 to 68 months). All five have two-ventricle circulation, two of the five patients requiring surgical enlargement of the right ventricular outflow tract with or without closure of the atrial septal defect. Echocardiographic tricuspid valve dimensions and Z-values before transcatheter valvotomy tended to be smaller in the patients who died than in the survivors. In the survivors, the absolute tricuspid valve dimensions increased after valvotomy but the Z-values tended to decrease or stayed constant. CONCLUSIONS: Transcatheter valvotomy is a good alternative to surgical valvotomy in patients with pulmonary atresia and intact ventricular septum. Two-ventricle circulation can be achieved despite subnormal right ventricular growth.

Deadenylation-dependent and -independent decay pathways for alpha1-tubulin mRNA in Chlamydomonas reinhardtii.

The alpha- and beta-tubulin mRNAs of Chlamydomonas reinhardtii exhibit different half-lives under different conditions: when expressed constitutively, they degrade with half-lives of about 1 h, whereas when induced by deflagellation, they degrade with half-lives of only 10 to 15 min. To investigate the decay pathway(s) used under these two conditions, an alpha1-tubulin gene construct which included an insert of 30 guanidylate residues within the 3' untranslated region was introduced into cells. This transgene was efficiently expressed in stably transformed cells, and the mRNA exhibited constitutive and postinduction half-lives like those of the alpha1-tubulin mRNA. Northern blot analysis revealed the occurrence of a 3' RNA fragment derived from the poly(G)-containing alpha1-tubulin transcripts. The 3' fragment was shown to accumulate as full-length mRNA disappeared in actinomycin D-treated cells, indicating a precursor-product relationship. Insertion of a second poly(G) tract upstream of the first resulted in accumulation of only a longer 3' fragment, suggesting that the decay intermediate is generated by 5'-to-3' exonucleolytic digestion. A translational requirement for generation of the 3' fragment was demonstrated by experiments in which cells were deflagellated in the presence of cycloheximide. Analysis of fragment poly(A) length revealed that the fragments were, at most, oligoadenylated in nondeflagellated cells but had a long poly(A) tail in deflagellated cells. These findings suggest that the oligoadenylated fragment is a decay intermediate in a deadenylation-dependent, constitutive degradation pathway and that the requirement for deadenylation is bypassed in deflagellated cells. This represents the first example in which a single transcript has been shown to be targeted to different decay pathways under different cellular conditions.

EPOC and the energetics of brief locomotor activity in Mus domesticus.

Excess post-exercise oxygen consumption (EPOC) is normally not considered in determinations of the metabolic cost of activity. This approach overlooks an important energetic cost that an animal incurs as a result of activity. To examine the importance of EPOC, we determined how the energetic cost of locomotion was affected by activity of short duration and high intensity. Mice were run at maximum speed on a treadmill while enclosed in an open-flow respirometry system. After sprinting for 5, 15, 30, or 60 sec, each mouse was allowed to recover while remaining enclosed in the respirometry chamber. Exercise oxygen consumption (EOC), the volume of oxygen consumed during the exercise, increased linearly with sprint duration. EPOC was determined as the volume of oxygen consumed after exercise ended until rest was reached. EPOC volumes were found to be constant following 5-60 sec of activity and accounted for > or = 90% of the total metabolic cost. The average EPOC volume of all treatments was 0.76 +/- 0.456 ml O2.gm-1. The net cost of activity (Cact), which considers both EOC and EPOC, decreased as sprint duration increased and varied between 500 ml O2.g-1.km-1 for 5 sec to 30 ml O2.g-1.km-1 for 60 sec of activity. The values for Cact were 15 to 250 times higher than traditional estimates of locomotor costs. From these data, it can be concluded that (1) EPOC is not affected by short exercise durations; (2) EPOC is an important energetic consideration when exercise durations are short; and (3) the metabolic costs of brief, vigorous locomotion may be much higher than previously estimated.

Differential regulation of interleukin-1alpha and interleukin-1beta in K-562 cells.

Interleukin (IL)-1alpha and IL-1beta are encoded by two separate genes, but both function as comitogens for lymphocyte activation. In this study, we observed K-562 cells to express constitutively mRNA for IL-1alpha, although IL-1alpha was not detected in the growth-conditioned medium (GCM). However, IL-1beta mRNA was not expressed unless the cells had been treated with phorbol myristate acetate (PMA). Both IL-1alpha and IL-1beta were detected in the GCM after the cells had been cultured with PMA, suggesting that IL-1 elaboration required PMA treatment. The K-562 cells treated with PMA differentiated to the myeloblastic stage, as observed by nuclear morphologic properties by electron microscopy. PMA treatment induced de novo expression of CD61 or gpIIIa, a marker associated with megakaryoblasts. These results showed that although K-562 cells constitutively expressed IL-1alpha mRNA, PMA treatment was required for secretion. On the other hand, both the expression and secretion of IL-1beta required treatment with PMA. This study showed that K-562 cells treated with PMA differentiated to the myeloblastic stage and expressed and secreted IL-1alpha and IL-1beta.

Single pass VDD pacing in children and adolescents.

Use of a single pass lead for VDD pacing in complete heart block is well described in adults, but there are only brief reports of its use in children. We have used standard adult size single pass leads in 13 children and adolescents aged 3.7-17.2 years (mean 10.1 years) and weighing 13.5-76 kg (mean 34.8 kg). Congenital complete heart block was present in 7 patients, surgical complete heart block in 5 patients and 2:1 AV block of unknown cause in 1 patient. In four patients, the VDD system was their first pacing system. In nine of the patients, 1-6 previous systems had been used and simultaneous extraction of ventricular leads and/or atrial leads was performed. Leads of four different types were used: Brilliant IMP15Q, Brilliant + IMR15Q, CapSure 5032, and Unipass 425-13 with 4 different generators: Saphir 600, Saphir II 620, Thera VDD 8948, and Unity 292-07. At implantation, via a subclavian vein puncture, excess lead was advanced into the right atrium to allow both atrial sensing and slack for further growth. Ventricular thresholds ranged from 0.2-0.7 V. The minimal atrial amplitude was 0.7-4 mV and the maximum amplitude was 2.5-8 mV. There were no complications. All patients have maintained adequate atrial signals for reliable pacing with follow up of 3-36 months (mean 17.6 months) during which time some have undergone considerable growth. Reliable atrial synchronous ventricular pacing is possible in growing children with complete heart block using a standard adult single pass lead.

Transcatheter closure of patent arterial ducts using controlled-release coils.

OBJECTIVE: To determine the efficacy of transcatheter closure of patent arterial ducts using controlled-release coils. DESIGN: Transcatheter closure of patent arterial ducts was attempted in 52 patients using controlled-release coils. SETTING: For the study, four tertiary paediatric cardiology units were used, two of which were in the U.K., one in Italy and one in Turkey. PATIENTS: The 52 patients ranged in age between 3-5 months and 61 years (median 3-5 years), and weighted between 4.5 kg and 62 kg. The duct diameters were 1 mm to 6.5 mm. RESULTS: In four patients the ducts were too large for safe release of the coils. In the remaining 48, one coil was inserted in 33 patients, two coils in nine, three coils in four and four coils in two patients. Immediately at the end of the procedure, the duct was completely occluded in 26/47 (55%) patients. Haemolysis occurred in one patient, in whom the coil was removed by a snare catheter and a large umbrella device was implanted with resolution of the haemolysis. Coil embolization to the pulmonary artery occurred in five (10%) patients. All were easily retrieved and replaced by larger coils. At the latest follow-up by colour Doppler echocardiography, the duct was completely occluded in 44/47 (94%) patients. CONCLUSIONS: Transcatheter closure of patent arterial ducts by controlled-release coils is effective and safe. Even when more than one coil is inserted the technique is still less cumbersome and considerably cheaper than transcatheter umbrella closure.

Surgical management of colorectal metastases to the liver: role of resection and cryosurgery.

Long-term results of 41 patients who underwent hepatic resection and early experience with 21 patients treated by hepatic cryosurgery alone or combined with resection for colorectal metastases are presented. Patients treated by resection had three or fewer metastases, no perioperative mortality, and a mean follow-up of 43.5 months. The five-year overall survival is 34% with a median survival of 48 months. By multivariate analysis, only transfusions correlated significantly with survival, but in a negative manner (p = 0.05). A mean of 4.3 units were transfused per patient, though only 25 patients actually received transfusions.

Evolving use of embolisation coils for occlusion of the arterial duct.

OBJECTIVE: To assess the outcome of arterial duct occlusion with coils chosen according to the duct morphology. DESIGN: Retrospective study. SETTING: Paediatric cardiology centre. PATIENTS: Coil occlusion was attempted in 57 patients aged 0.5 to 15 (median 3.7) years and weighing 5-59 (median 14) kg between January 1991 and December 1995. A residual leak was present in 8 patients after umbrella closure and in 4 patients after duct ligation. METHODS: Coils of 4 different types were implanted through 4 or 5 F femoral artery catheters. Platinum or Interlocking Detachable 0.018 inch coils were deployed completely inside tubular ducts. Gianturco or PDA controlled release 0.038 inch coils were implanted to straddle short, post ligation and post umbrella ducts. RESULTS: Coil implantation was successful in 54/57 patients. At 1 year the cumulative occlusion rate was 53/57 ducts (93%) on an intention to treat analysis. A single coil was implanted in 37 (69%), 2 coils in 10 (19%), 3 coils in 3 (5%) and 4 coils in 4 (7%) of the 54 successful procedures. Duct occlusion was documented at the end of the procedure in 31%, by the following day in 83%, by 6 weeks in 87%, by 6 months in 96%, and by 1 year in 98%. Coil embolisation occurred in 6/58 procedures (10%), with a 50% rate in the first year of implantation (1/2 patients) falling to 7% in the last year (3/42 patients). All embolised coils were easily retrieved. CONCLUSIONS: Occlusion of small to moderate size arterial ducts, including residual post umbrella or post ligation ducts, was readily accomplished by coils selected according to the duct anatomy. This has both cost and practical benefits.

Medium-term results of experimental stent implantation into the ductus arteriosus.

Balloon dilation is disappointing in maintaining patency of the arterial duct. In neonatal lambs, stent implantation in the arterial duct results in significantly larger ducts with greater pulmonary blood flow than balloon dilation. Little is known, however, about the duration of duct patency after stent implantation. The outcome of stent implantation into the arterial duct in 12 lambs was observed over a period of 1 to 24 months. Stents (Wallstent in 9, Tower stent in 3) were implanted after recanalizing the occluded duct at 2 to 7 days of age. Heparin was given only during the procedure, but no further anticoagulants were used. Angiographic or postmortem evaluations were made at 1, 1.5, 2, 3, 4, 6, 12, 16, and 21 months in a subgroup of 9 lambs who did not undergo reinterventions. The duct was patent in all these except for one studied at 16 months. Neointima initially developed in the center of the stent before extending toward the orifices, eventually burying the metal strands in contact with the wall. From 4 to 6 months onward stenoses were present inside some of the stents. When the stent did not protrude into the aorta, neointima extended over the duct orifice. Metal strands that were not in contact with the duct wall were incompletely covered with endothelial cells, platelets, and fibrin strands, but no thrombi were noted. Late balloon dilation of the stented duct was performed in two lambs increasing the pulmonary artery blood flow. In one lamb the neointimal lining was successfully removed at 14 months with an atherectomy catheter. Stent implantation into the arterial duct can maintain patency up to 21 months and could be considered as an alternative to neonatal systemic to pulmonary artery shunt operations. Neointimal proliferation and stenosis formation, however, is a major limitation that may eventually lead to a reduction in the pulmonary artery blood flow.