Ripple Frequency Determined via a Novel Algorithm Is Associated With Atrial Fibrillation Termination and Freedom From Atrial Fibrillation.

Background: Persistent atrial fibrillation (AF) is a complex arrhythmia, and attaining freedom from AF with ablation has been challenging. Objectives: This study evaluated a novel CARTO software algorithm based on the CARTO Ripple map for AF termination and 18-month freedom from AF. Methods: Consecutive patients who underwent first-time ablation for persistent AF were included. A high-density Ripple map was created using a Pentaray catheter. Following PVI, ablation was performed at locations with rapid Ripple activations, a protocol previously described by us. Patients were followed for 18 months to assess rhythm outcomes. A retrospective analysis was performed using the CARTO Ripple frequency software algorithm. The Ripple frequency algorithm quantifies amplitude changes in the bipolar electrogram. Results: A total of 115 AF maps were analyzed from 84 patients (mean age 65.9 years, 63.1% men). The top quartile of Ripple frequency corresponded to a visual reference with 96.7% sensitivity and 91.1% specificity. AF terminated during ablation in 88.1% of patients: pulmonary vein antrum alone (14.9%) or pulmonary vein plus nonantral sites (85.1%). The top quartile of Ripple frequency was present in nonantral areas associated with AF termination with 90.2% sensitivity and 86.5% specificity. After 14.0 ± 6.5 months and 1.2 ± 0.4 ablations, 78 (92.9%) of 84 patients were free of AF, and 79.8% were free of any atrial arrhythmia. Conclusion: A novel algorithm for automated analysis of CARTO Ripple frequency demonstrated good sensitivity and specificity for detecting atrial regions in persistent AF in which ablation is associated with frequent AF termination and freedom from AF during follow-up.

Ventricular Tachycardia (VT) Substrate Characteristics: Insights from Multimodality Structural and Functional Imaging of the VT Substrate Using Cardiac MRI Scar, 123I-Metaiodobenzylguanidine SPECT Innervation, and Bipolar Voltage.

Postischemic adaptation results in characteristic myocardial structural and functional changes in the ventricular tachycardia (VT) substrate. The aim of this study was to compare myocardial structural and functional adaptations (late gadolinium enhancement/abnormal innervation) with detailed VT mapping data to identify regional heterogeneities in postischemic changes. Methods: Fifteen patients with ischemic cardiomyopathy and drug-refractory VT underwent late gadolinium enhancement cardiac MRI (CMR), 123I-metaiodobenzylguanidine SPECT, and high-resolution bipolar voltage mapping to assess fibrosis (>3 SDs), abnormal innervation (<50% tracer uptake), and low-voltage area (<1.5 mV), respectively. Three-dimensional reconstructed CMR/123I-metaiodobenzylguanidine models were coregistered for further comparison. Results: Postischemic structural and functional adaptations in all 3 categories were similar in size (reported as median [quartile 1-quartile 3]: CMR scar, 46.1 cm2 [33.1-86.9 cm2]; abnormal innervation, 47.8 cm2 [40.5-68.1 cm2]; and low-voltage area, 29.5 cm2 [24.5-102.6 cm2]; P > 0.05). However, any single modality underestimated the total VT substrate area defined as abnormal in at least 1 of the 3 modalities (76.0 cm2 [57.9-143.2 cm2]; P < 0.001). Within the total VT substrate area, regions abnormal in all 3 modalities were most common (25.2%). However, significant parts of the VT substrate had undergone heterogeneous adaptation (abnormal in <3 modalities); the most common categories were "abnormal innervation only" (18.2%), "CMR scar plus abnormal innervation only" (14.9%), and "CMR scar only" (14.6%). All 14 VT channel/exit sites (0.88 ± 0.74 mV) were localized to myocardium demonstrating CMR scar and abnormal innervation. This specific tissue category accounted for 68.3% of the CMR scar and 31.2% of the total abnormal postischemic VT substrate area. Conclusion: Structural and functional imaging demonstrated regional heterogeneities in the postischemic VT substrate not appreciated by any single modality alone. The coexistence of abnormal innervation and CMR scar may identify a particularly "proarrhythmic" adaptation and may represent a potential novel target for VT ablation.

Validation of a novel CARTOSEG™ segmentation module software for contrast-enhanced computed tomography-guided radiofrequency ablation in patients with atrial fibrillation.

INTRODUCTION: Visualization of left atrial (LA) anatomy using image integration modules has been associated with decreased radiation exposure and improved procedural outcome when used for guidance of pulmonary vein isolation (PVI) in atrial fibrillation (AF) ablation. We evaluated the CARTOSEG™ CT Segmentation Module (Biosense Webster, Inc.) that offers a new CT-specific semiautomatic reconstruction of the atrial endocardium. METHODS: The CARTOSEG™ CT Segmentation Module software was assessed prospectively in 80 patients undergoing AF ablation. Using preprocedural contrast-enhanced computed tomography (CE-CT), cardiac chambers, coronary sinus (CS), and esophagus were semiautomatically segmented. Segmentation quality was assessed from 1 (poor) to 4 (excellent). The reconstructed structures were registered with the electroanatomic map (EAM). PVI was performed using the registered 3D images. RESULTS: Semiautomatic reconstruction of the heart chambers was successfully performed in all 80 patients with AF. CE-CT DICOM file import, semiautomatic segmentation of cardiac chambers, esophagus, and CS was performed in 185 ± 105, 18 ± 5, 119 ± 47, and 69 ± 19 seconds, respectively. Average segmentation quality was 3.9 ± 0.2, 3.8 ± 0.3, and 3.8 ± 0.2 for LA, esophagus, and CS, respectively. Registration accuracy between the EAM and CE-CT-derived segmentation was 4.2 ± 0.9 mm. Complications consisted of one perforation (1%) which required pericardiocentesis, one increased pericardial effusion treated conservatively (1%), and one early termination of ablation due to thrombus formation on the ablation sheath without TIA/stroke (1%). All targeted PVs (n  =  309) were successfully isolated. CONCLUSIONS: The novel CT- CARTOSEG™ CT Segmentation Module enables a rapid and reliable semiautomatic 3D reconstruction of cardiac chambers and adjacent anatomy, which facilitates successful and safe PVI.

Impact of conversion on short and long-term outcome in laparoscopic resection of curable colorectal cancer.

INTRODUCTION: Long-term outcome of patients following conversion during laparoscopic surgery for colorectal cancer is not often reported. Recent data suggest a negative impact of conversion on long-term survival. This study aimed to evaluate the impact of conversion on the perioperative outcome and on long-term survival in patients who underwent laparoscopic resection for curable colorectal cancer. METHODS: Evaluation of our prospective in-hospital collected data of patients who underwent laparoscopic surgery for curable colorectal cancer over a 5-year period. Long-term data were collected from our outpatient's clinic data and personal contact when necessary. RESULTS: During the study period, 175 patients were operated on laparoscopically for curable colon cancer (stage I-III). Mean follow-up was 33±18 months with a minimum follow-up of 12 months. For various reasons, 25 patients (14.4%) had to be converted to open surgery. Short-term outcome revealed a trend towards longer operations, a higher rate of surgical complications, and a longer hospital stay in the converted group. Five-year, Kaplan-Meier, disease-free analysis was worse for converted patients. Overall survival did not differ between the 2 groups. Cox proportional hazards regression analysis revealed that conversion and AJCC stage were independent risk factors for recurrence. CONCLUSIONS: Conversion in laparoscopic surgery for curable colorectal cancer is associated with a worse perioperative outcome and worse disease-free survival.

Current changes in the management and outcome of patients with curable colorectal cancer.

BACKGROUND: Major changes in the evaluation and treatment of curable colorectal cancer (CRC) have emerged in the last two decades. These changes have led to better patient outcome overtime. OBJECTIVES: To evaluate the impact of these changes as reflected in the difference in long-term outcome of a consecutive group of recently laparoscopically operated curable CRC patients and a consecutive group of patients operated 20 years earlier in the same department. METHODS: Data of the new group were taken from our prospectively collected data of patients who underwent elective laparoscopic surgery for CRC in recent years. Data regarding patients operated on 20 years ago were retrieved from previous prospectively collected data on the long-term survival of CRC patients operated in the same department. RESULTS: The recently operated group comprised 203 patients and the previous group 199 patients. Perioperative mortality was 0.5% in the new group versus 1.5% in the old group (not significant). There were more early-stage and more proximal tumors in the recently operated group. A Kaplan-Meier 5-year survival analysis revealed no difference between stage I patients of the two groups. However, there was a significant increase in 5-year survival in the new group for stage II (85% vs. 63%, P = 0.004) and for stage III patients (57% vs. 39%, P = 0.01). This trend was maintained after removing the rectal cancer patients from the calculated data. CONCLUSIONS: We have demonstrated improved survival for stage II and ILL CRC patients overa 20-year period in the same medical center. This change most likely reflects advances both in imaging techniques leading to more accurate staging and in adjuvant treatments.

[Initial experience with collagen plug for the treatment of complex anal fistula].

INTRODUCTION: Anorectal fistulas are a communication between the anal canal or the rectum to the perineum, which are generally formed by an infectious process of the submucosal glands. Surgery is the treatment of choice for these fistulas with preservation of the anal sphincters function, and hence continence, mandatory. Recently, however, some articles published suggested that the use of anal fistula plugs, instead of surgery, leads to better results. This study was designed to evaluate the use of anal fistula plugs in patients with trans-sphincteric anal fistulas. METHODS: A series of 10 consecutive patients were treated in our proctology department for complex fistulas with anal fistula plugs and were evaluated with subsequent follow-up. During the operation the fistula tract was identified and the plug was inserted and fixed by internal and external sutures. RESULTS: Ten patients, with a median age 40.8 years were included. There were 6 males and 4 females. At median length of follow-up of 12 months [range: 8 to 16 months] 5 of the 10 fistulas had healed (50%). CONCLUSION: The anal fistula plug is successful in the treatment of anorectal fistulas. Due to its low morbidity rate the insertion of anal fistula plugs should be considered instead of surgery.

Correlation of CO2 pneumoperitoneal pressures between rodents and humans.

INTRODUCTION: Many studies have reported on the effects of pneumoperitoneum in a rat model, using a wide range of intra-abdominal pressures. The correlation between pneumoperitoneal pressures in rodents to pressures in humans has not been established. This study evaluates changes in various physiological parameters in different pneumoperitoneum pressures in the rat model with a comparison to known data in humans. MATERIALS AND METHODS: Three groups of eight Wistar rats each were anesthetized, tracheostomized, and mechanically ventilated with fixed tidal volume and respiratory rate. After a stabilization phase, CO(2) pneumoperitoneum was established to 12, 8, and 5 mmHg in the different groups. Changes in blood pressure, heart rate, peak ventilatory pressure, and end-tidal CO(2) (ETCO(2)) were recorded throughout the experiment. RESULTS: There were no significant changes in blood pressure and heart rate in all groups. No increase in ETCO(2) was demonstrated following induction of pneumoperitoneum in the 12 and 8 mmHg groups. A statistical significant increase in ETCO(2) occurred only in the 5 mmHg group (39.4 to 41.3 mmHg, p = 0.023). Ventilatory pressures increased after induction of pneumoperitoneum in all groups. The increase reached a maximal level in the 8 and 12 mmHg groups (from 3 to 12 mmHg) and was lower in the 5 mmHg group (from 3 to 7 mmHg) CONCLUSIONS: The neglected increase in ETCO(2) in pressures > or =8 mmHg, in the rat correlates to high pressures in humans (above 14-20 mmHg) when CO(2) diffusion through the peritoneum declines due to pressure occlusion of peritoneal capillaries. The maximal ventilatory pressures generated in the rat in intra-abdominal pressures > or =8 mmHg correlate to pressures, which are higher than the standard working pressures in humans. Thus, pneumoperitoneal pressures >8 mmHg in the rat do not simulate routine working pressures employed in humans. A pressure of 5 mmHg is optimal in a rat model to simulate laparoscopy in humans.

Laparoscopic surgery for colorectal polyps.

BACKGROUND: Size, location, and type of colonic polyps may prevent colonoscopic polypectomy. Laparoscopic colectomy may serve as an optimal alternative in these patients. We assessed the perioperative outcome and the risk for cancer in patients operated on laparoscopically for colonic polyps not amenable to colonoscopic resection. METHODS: An evaluation was conducted of our prospective accumulated data of a consecutive series of patients operated on for colonic polyps. RESULTS: Sixty-four patients underwent laparoscopic resection for colonic polyps during a 6-year period. This group comprised 18% of all our laparoscopic colorectal procedures. Forty-six percent were males, mean age was 71. Most of the polyps (66%) were located on the right side. No deaths occurred. Conversion was necessary in 3 patients (4.6%). Significant complications occurred in 3 patients (4.6%). Nine patients (14%) were found to have malignancy. Three of them had lymph-node involvement. No difference existed in polyp size between malignant and nonmalignant lesions. CONCLUSIONS: Laparoscopic colectomy for endoscopic nonresectable colonic polyps is a safe, simple procedure as reflected by the low rate of conversions and complications. However, invasive cancer may be found in the final pathology following surgery. This mandates a strict adherence to surgical oncological principles. Polyp size cannot predict the risk of malignancy.

[Obstructed defecation syndrome].

Constipation has always been a common problem but recently it appears to be on the rise in the western world. Its prevalence in the general population is estimated at around 20% with reports suggesting significantly higher levels in the elderly, especially above the age of 65. There have also been reports of females being affected more then males, Higgins et al reporting a male to female ratio of 1: 2.2. Constipation can be classified as either primary or secondary. Primary constipation is either due to prolonged transient time through the colon (colonic inertia) or a disturbance in defecation with normal transient time. Secondary constipation is either due to medications or other medical diseases for example hypothyroidism, diabetes or Parkinson's disease. In the past several years advances have been made in understanding the physiological and pathophysiological processes of normal and abnormal defecation. This has led to the understanding of transient time, sensation and pressure build-up in the rectum and anus as well as the key role of synchronization between contraction and relaxation of the involved muscles and sphincters. Disturbance in any one of the above mentioned processes can lead to constipation. The obstructed defecation syndrome has been shown to be the result of an abnormal function of the muscles involved in defecation or an anatomical abnormality of the pelvic organs. Obstructed defecation syndrome is estimated to be prevalent in 7% of the adult population and is judged to be the cause of one third of all cases of constipation. Due to the fact that surgery is an emerging treatment of choice for these patients suffering from obstructed defecation syndrome, it is highly important that we should not only be able to diagnose the cause of constipation in patients but accurately identify those suffering specifically from obstructed defecation syndrome. Therefore, this paper reviews the definitions, symptoms, pathophysiology, diagnosis and treatments of obstructed defecation syndrome.

An extension of the Minute Virus of Mice tissue tropism.

Well-defined tissue tropism makes Autonomous Parvoviruses a valuable model for studies of virus-cell interactions and gene therapy research. We developed a new Minute Virus of Mice variant, different from the known prototype (MVMp) and immunosuppressive (MVMi) strains. The new virus variant, designated F1, was isolated from the culture of semi-permissive Fisher Rat Fibroblasts, F111, infected with MVMp. The F1 genome carried point mutations in regions known to determine the mutually restricted host ranges of MVMp and MVMi. In F111 cells, F1 cytotoxicity, gene expression and multiplication were significantly higher compared to MVMp. Conversely the wild-type virus propagated in MVMp-permissive cells more efficiently than the F1. Reversion of the F1-specific mutations to wild-type MVMp sequence, following reverse-passaging of the mutant virus in MVMp-permissive cells, confirmed a specific adaptation of the F1 virus to F111 cells. Considerable divergence in tissue specificities between the wild-type and mutant viruses was demonstrated in vivo.

[Anal mucinous adenocarcinoma arising in long standing fistula-in-ano].

Perianal mucinous adenocarcinoma is an unusual but well described malignancy constituting approximately 3 to 11% of all anal carcinoma. The pathology is thought to develop from one of three types, the distal part of the rectum, the mucin-secreting columnar epithelium of the anal glands, and from chronic fistula-in-ano. The association of carcinoma with anal fistula may manifest itself in several ways: a fistula may be associated with cancer elsewhere in the colon; cancer may present as a fistula; or cancer may develop in anal fistula. Mucinous adenocarcinoma of the anus supervening on a long-standing chronic anal fistula is an extremely rare disease with less then 150 cases reported in the literature, mainly single patient reports. The key to long-term survival seems to be a high index of suspicion in those patients with longstanding perianal fistula. Chemotherapy in combination with external beam radiation followed by abdomino-perineal resection seems to be the most appropriate therapy.

Host cell specificity of minute virus of mice in the developing mouse embryo.

Productive infection by the murine autonomous parvovirus minute virus of mice (MVM) depends on a dividing cell population and its differentiation state. We have extended the in vivo analysis of the MVM host cell type range into the developing embryo by in utero inoculation followed by further gestation. The fibrotropic p strain (MVMp) and the lymphotropic i strain (MVMi) did not productively infect the early mouse embryo but were able to infect overlapping sets of cell types in the mid- or late-gestation embryo. Both MVMp and MVMi infected developing bone primordia, notochord, central nervous system, and dorsal root ganglia. MVMp exhibited extensive infection in fibroblasts, in the epithelia of lung and developing nose, and, to a lesser extent, in the gut. MVMi also infected endothelium. The data indicated that the host ranges of the two MVM strains consist of overlapping sets of cell types that are broader than previously known from neonate and in vitro infection experiments. The correlation between MVM host cell types and the cell types that activate the transgenic P4 promoter is consistent with the hypothesis that activation of the incoming viral P4 promoter by the host cell is one of the host range determinants of MVM.

Viral inoculation of mouse embryos in utero.

A technique is described for the injection of live virus into early- and mid-gestation mouse embryos in utero. The procedure is quick, easy, harmless to the embryos, and does not require specialized surgical or microinjection equipment. Since the developing embryo contains most different cell types in a very wide range of differentiation states, the procedure permits a rapid and near complete characterization of the host cell type range in a single experimental system. Under anaesthesia, a simple laparotomy was used to reveal the uterine horns of 9.5 or 12.5 days post-conception(dpc) females. One uterine horn was deflected onto the ventral abdominal surface. Embryos were injected through the uterine wall and the uterine horn replaced into the abdominal cavity. The entire operation could be completed in 10-15 min without distinguishable pain to the mother or adverse effect on the pregnancy. The procedure is presented in sufficient detail to permit its ready adoption in situations where a more complete characterization of host cell type range is sought.

A replacement for methoxyflurane (Metofane) in open-circuit anaesthesia.

Methoxyflurane (Metofane) has been widely used as an open-circuit anaesthetic in small laboratory animals for several decades. Its low vapour pressure and high blood solubility have permitted its use in convenient and simple drop-chamber/nose-cone setups. Recently, following the decision by the primary manufacturer to discontinue production, it has become increasingly difficult to obtain methoxyflurane. We describe here a simple and effective adaptation of isoflurane, an excellent inhalation anaesthetic, to open-circuit drop-chamber/nose-cone anaesthesia. It was found that the vapour concentration of isoflurane could be continuously varied by dissolving the anaesthetic in propylene glycol and that a 20% solution produced effective anaesthesia such that in adult mice, 2 ml of 20% isoflurane in propylene glycol induced anaesthesia within 2 min in a one-litre drop chamber. Furthermore, anaesthesia maintenance with 20% isoflurane was tested in two sets of mice. In one set, surgical plane anaesthesia was maintained for 10 min in a head chamber. After removal of the chamber, the animals awoke within one minute and recovered without any indication of post-anaesthetic distress. The second set contained pregnant mice; here anaesthesia was maintained for between 10 and 12 min, during which laparotomy, exposure of one uterine horn, intrauterine injection and wound closure were completed. The recovery from anaesthesia was also within a minute and with no signs of distress. Healthy litters were delivered after a normal gestation. This isoflurane/propylene glycol procedure is simple, effective and humane, and is a good substitute for methoxyflurane.