Proposal for a post-operative surveillance strategy for stage I colorectal cancer patients based on a novel recurrence risk stratification: a multicenter retrospective study.

BACKGROUND: The recurrent risk of stage I colorectal cancer (CRC) is not clear, and the data regarding appropriate post-operative surveillance schedules in stage I CRC are scarce. OBJECTIVES: We aimed to stratify stage I CRC based on the recurrence risk and evaluate optimal post-operative surveillance durations based on this stratification. METHODS: We retrospectively analyzed the cases of 6607 stage I CRC patients from 24 institutions. To assess the patients' clinicopathological factors that impact recurrence-free survival (RFS), we performed univariate and multivariate analyses using Cox proportional hazards models. We divided the patients into classes based on their numbers of factors that were associated with poor RFI in the multivariate analysis. RESULTS: Recurrence occurred in 3.9% patients. The multivariate analysis revealed the independent factors for poor RFS: rectal cancer, T2 depth, presence of lymphatic invasion, high level of pre-operative carcinoembryonic antigen, and absence of D2-3 lymphadenectomy. We also divided the patients into three classes based on their numbers of these risk factors; the 3-year and 5-year RFS rates were 99.3% and 99.1% in the no-risk patients, 97.4% and 96.5% in the patients with 1-2 risks, and 92.1% and 90.0% in the patients with 3-5 risks, respectively. In the patients with no risk and in the patients with 1-2 risks after 3 years post-surgery, ≤ 1% recurrence occurred. Thus, post-operative surveillance may be omitted in these populations. CONCLUSIONS: Our new classification properly stratified the recurrence risks of stage I CRC patients, and may help reduce unnecessary post-operative surveillance.

Significance of the 7th postoperative day neutrophil-to-lymphocyte ratio in colorectal cancer.

PURPOSE: High neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and is associated with poor survival in localized or metastatic cancer. Preoperative NLR in colorectal cancer reportedly correlates with recurrence-free survival and is useful as a recurrence prediction factor. No reports have yet investigated recurrence factors using postoperative NLR. This study assessed the predictive value of NLR preoperatively and on the first (NLR1) and seventh day (NLR7) postoperatively in patients with stage II colorectal cancer. METHODS: We performed a retrospective cohort study involving patients undergoing colorectal resection at a single institution between January 2012 and December 2016; we used medical records of 176 consecutive patients with stage II colorectal cancer undergoing curative tumor resection. NLRs as well as clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with recurrence-free survival (RFS). RESULTS: Univariate analysis revealed that elevated NLR, NLR7, and lymphatic invasion were significantly associated with decreased RFS (p < 0.05). NLR7 was revealed as significant via multivariate analysis (p = 0.013). The 3-year RFS rate was 87.1% for patients with normal NLR7 and 70.3% for those with elevated NLR7. CONCLUSION: Elevated seventh-day postoperative NLR is a significant independent predictor of reduced RFS for patients with stage II colorectal cancer and may be a potential biomarker for identifying candidates for adjuvant chemotherapy.

Angiotensin I-converting enzyme inhibitors/angiotensin II receptor blockers may reduce tumor recurrence in left-sided and early colorectal cancers.

BACKGROUND: Angiotensin signaling is suggested to be involved in tumorigenesis, tumor proliferation, and metastases. In colorectal cancer (CRC), it was demonstrated that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may reduce the risk of CRC; however, their impact on tumor recurrence remains unknown. Therefore, in this study, we evaluated the impact of ACEIs/ARBs on tumor recurrence in CRC patients. PATIENTS AND METHODS: We retrospectively investigated the clinicopathological data of 461 stage I-III CRC patients. We divided the patients into those who took an ACEI and/or ARB (the ACEI/ARB+ group) and those who did not (the ACEI/ARB- group), and we compared the two groups' recurrence-free survival (RFS) using a Kaplan-Meier curve analysis and log rank test. We also examined the impact of AGTR1 expression on tumor recurrence, using two public CRC datasets. RESULTS: The Kaplan-Meier curves showed a trend toward improved RFS in the ACEI/ARB+ group versus the ACEI/ARB- group (p = 0.063). Subgroup analyses demonstrated that the RFS was significantly better in the ACEI/ARB+ group versus the ACEI/ARB- group in the patients with left-sided CRC (p = 0.030) and those with stage I CRC (p = 0.009). Consistent with these findings, the AGTR1 expression was higher in the left-sided versus right-sided colon (p = 0.048). High AGTR1 expression levels were associated with poor RFS in the GSE39582 dataset's stage I-III CRC patients (p < 0.001), and this finding was also validated in the GSE17536 dataset (p = 0.023). CONCLUSION: ACEI/ARB treatment may reduce tumor recurrence in left-sided CRC and early-stage CRC.

G12V and G12C mutations in the gene KRAS are associated with a poorer prognosis in primary colorectal cancer.

PURPOSE: The increased incidence of colorectal cancer (CRC) has necessitated the development of novel prognostic and predictive factors from which new diagnostic tests could evolve. Evidence suggests the KRAS gene represents such a factor; its mutations are considered to be early indicators of CRC progression. This study assessed the prognostic impact of specific known KRAS codon 12/13 mutations on survival in patients with CRC. METHODS: Formalin-fixed paraffin-embedded tissue blocks or sections from primary were obtained from patients registered between 2014 and 2016 for genomic DNA extraction. KRAS gene was analyzed by direct sequencing or Luminex assay. The primary endpoint was the frequency of KRAS gene mutations and the secondary endpoints were differences in KRAS mutation rates by various stratification factors. Univariate and multivariate analyses were performed to investigate relationships between KRAS mutation rates and patient background factors. RESULTS: Sequencing of 200 CRC primary tumor samples demonstrated 74 (37.5%) with KRAS mutations in codons 12 (77%; 57/74) and 13 (23%; 17/74), all of which were TNM stages I-III. Tumors with KRAS mutations were more frequently located in the right side of the colon. Multivariate analysis indicated that G12V or G12C mutations were associated with poor prognosis [hazard ratio (HR) = 3.77, 95% confidence interval (CI), 1.54-8.39 and HR = 6.57; 95% CI, 1.90-17.7, respectively] in terms of recurrence-free survival. CONCLUSION: KRAS codon 12G-to-V or G-to-C mutations are independent prognostic factors in patients with stage I-III CRC.

A case of intussusception developed at the site of ileocolic anastomosis after laparoscopic right hemicolectomy.

BACKGROUND: Intussusception is a relatively common condition seen in children. In comparison, adult intussusception is rare and usually occurs as a complication in patients with organic diseases. It is responsible for 1% of all bowel obstructions, in most of intussusceptions a malignant tumor is involved. Herein, we present an extremely unusual case of intussusception that occurred as a complication at the site of a functional end-to-end anastomosis. CASE PRESENTATION: A 57-year-old female patient was diagnosed with tumors in the ascending and descending colon and was referred to our department. Laparoscopic hemicolectomy and laparoscopic descending colectomy were performed. The mechanical intestinal obstruction occurred on the 9th day postoperatively, and computed tomography scan revealed intussusception at the site of the ileocolic anastomosis. Endoscopic reduction was attempted, but the procedure was challenging. Surgery was then performed and revealed that the site of ileocolic anastomosis firmly adhered to the side wall and right retroperitoneum. However, the intestine in the oral side of the anastomosis was not fixed. Examination of the anastomotic site revealed that the ileum had passed through the anastomosis and prolapsed into the transverse colon. The ileocolic anastomosis was resected. End-to-end anastomosis was performed, and surgery was then completed. No neoplastic lesions were observed in the resected tissue of the lead point of intussusception. The postoperative clinical course was favorable, and the patient was discharged on the 11th day after the second round of surgery. CONCLUSIONS: There are no reports the anastomosis is involved as part of the intussception, as observed in the present case. Intussusception should thus be considered as one of the causes of postoperative mechanical intestinal obstruction.

A rare case of perivascular epithelioid cell tumor (PEComa) of the greater omentum.

BACKGROUND: A tumor composed exclusively or predominantly of human melanin black 45 (HMB45)-positive epithelioid cells is called a perivascular epithelioid cell tumor (PEComa). We report a very rare case of a PEComa of the greater omentum. CASE PRESENTATION: MRI conducted to examine the orthopedic disease of the patients, a 49-year-old Japanese woman, also identified a tumor in her pelvis. A CT scan revealed a tumor mass on the right side of the pelvic floor and clear nutrient vessels originating from the splenic and celiac arteries. An omental primary tumor or accessory spleen was thus suspected, and tumor resection was performed. The tumor was a light brown solid tumor with a smooth margin, measuring 5.2 × 3.8 × 3.5 cm. Histopathologically, the tumor was composed mainly of spindle and epithelioid cells, and large and small blood vessel formation was observed. In the immunohistochemical staining, tumor cells were positive for human melanin black 45 (HMB-45) and Melan-A and partially positive for alpha-smooth muscle actin. The final diagnosis was PEComa of the greater omentum. CONCLUSIONS: Although omental PEComa is very rare, it should be considered as a differential disease of an omental primary tumor.

A case of Wolff-Parkinson-White syndrome presenting spontaneous mutual frequent transition between atrioventricular reciprocating tachycardia and atrioventricular nodal re-entrant tachycardia.

Atrioventricular reciprocating tachycardia (AVRT) and atrioventricular nodal re-entrant tachycardia (AVNRT) can coexist and present unidirectional transition (from AVRT to AVNRT, or from AVNRT to AVRT) in a single patient. Actually, such cases have already been reported previously. However, a case with spontaneous bidirectional transition of both tachycardias during supraventricular tachycardia has never been reported. This article describes a case with spontaneous, mutual, and frequent transition between AVRT and AVNRT.

Efficacy of Left Atrial Voltage-Based Catheter Ablation of Persistent Atrial Fibrillation.

BACKGROUND: Low-voltage zones (LVZs) represent fibrotic tissue and are substrates for atrial fibrillation (AF). We hypothesized that LVZ-based substrate modification along with pulmonary vein isolation (PVI) would improve outcomes in persistent AF (PeAF) patients with LVZs, whereas PVI alone would work in patients without LVZs. METHODS AND RESULTS: Voltage mapping of the left atrium (LA) was performed during sinus rhythm in 101 PeAF patients in whom LVZ was defined as an area with bipolar electrograms <0.5 mV. Thirty-nine patients had LVZs and underwent ablation of the entire LVZ area after PVI (LVZabl group). In the remaining 62 patients without LVZs, PVI alone was performed with no further substrate modifications (PVI group). An additional group of 16 consecutive PeAF patients with LVZ did not undergo any substrate modification after PVI and were used as a comparison group (LVZnon-abl group) despite having similar size of LVZs to that in the LVZabl group. After a single session, 28 (72%) patients in the LVZabl group had no recurrence, whereas 49 (79%) patients in the PVI group had no recurrence during 18 ± 7 months of follow-up (log-rank, P = 0.400). In the LVZnon-abl group, only 6 patients (38%) had no recurrence during 32 ± 7 months of follow-up, even after a mean number of sessions of 1.8 (log-rank, P < 0.001, compared with the LVZabl group). CONCLUSIONS: Additional LVZ-based substrate modification after PVI improved the outcome in PeAF patients with LVZs, whereas PVI alone worked in patients without LVZs, even in those with PeAF.

Spatial Relation Between Left Atrial Anatomical Contact Areas and Circular Activation in Persistent Atrial Fibrillation.

INTRODUCTION: Atrial low-voltage zones (LVZs) may be related to maintenance of atrial fibrillation (AF). The influence of left atrial (LA) contact areas (CoAs) on reentrant or rotor-like sources maintaining AF has not been investigated. METHODS AND RESULTS: Forty patients with persistent AF (PsAF) were analyzed. Three representative CoA regions in the LA (ascending aorta: anterior wall; descending aorta: left inferior pulmonary vein; and vertebrae: posterior wall) were visualized by enhanced CT. Using circular catheters, the LVZs (<0.5 mV) were assessed after restoration of SR, and local activation mapping and frequency domain analyses were performed after induction of AF. Circular activation during AF was visually defined as sites with ≥2 rotations by serial electrograms encompassing >80% of the mean AF cycle length. A pivot was defined as the core of the localized circular activation. Anterior (39/40 patients, 98%), left pulmonary vein antrum (27/40, 68%), and posterior (19/40, 48%) CoAs were identified, and 80% (68/85) of those sites were overlapped by or close (<3 mm) to LVZs. Thirty-six (90%) patients demonstrated circular activation (3.1±1.7 sites/patients) along with significantly higher organized dominant frequencies (6.3 ± 0.5 Hz, regularity-index: 0.26 [0.23-0.41]) within the LA, and the average electrogram amplitude of those pivots was 0.30 mV (0.18-0.52). Of those sites, 55% (66/120) were located at or close to CoA regions. Catheter ablation including of LVZs neighboring CoAs terminated AF in 9 (23%) patients. CONCLUSIONS: External anatomical structures contacting the LA may be related to unique conduction properties in diseased myocardium necessary for PsAF maintenance.

Long-term results of pulmonary vein antrum isolation in patients with atrial fibrillation: an analysis in regards to substrates and pulmonary vein reconnections.

AIMS: To examine the impact of left atrial (LA) low-voltage zones (LVZs) on atrial fibrillation (AF) recurrence after pulmonary vein antrum isolation (PVAI) without LA substrate modification. METHODS AND RESULTS: Seventy-six patients with AF (paroxysmal/persistent 65/11) were prospectively enroled. Left atrial voltage maps were constructed during sinus rhythm using NavX to identify LVZs (<0.5 mV), and PVAI without any LA substrate modification was performed using an open-irrigation catheter. After PVAI, 20 mg of adenosine triphosphate (ATP) was injected. Adenosine triphosphate-induced PV reconnections were eliminated by touch-up ablation when unmasked. Voltage maps revealed LVZs in 24 patients (32%) and no LVZs in 52 (68%). During 24 ± 7 months of follow-up, 15 patients (63%) with LVZs and 10 (19%) without had AF recurrences off antiarrhythmic drugs (log-rank P < 0.001). A multivariate logistic regression analysis revealed that LVZ areas [odds ratio (OR): 1.12 per 1 cm(2), 95% confidence interval (CI): 1.04-1.23, P = 0.001] and ATP-induced reconnection (OR: 2.08, 95% CI: 1.01-4.91, P = 0.046) were significant predictors of recurrence. In those with LVZs, the LVZ area was strongly correlated with the LA body volume (r = 0.81, P < 0.001) and a unique predictor of recurrence (OR: 1.17 per 1 cm(2), 95% CI: 1.01-1.55, P = 0.031), while in those without an LVZ, ATP-induced PV reconnection was a unique predictor (OR: 3.24, 95% CI: 1.15-15.39, P = 0.025). CONCLUSION: The LVZ area was an independent predictor of recurrence after PVAI without any LA substrate modification. Adenosine triphosphate-induced PV reconnection was also an independent predictor, especially in those without LVZs.

Clinicopathological features of acute megakaryoblastic leukaemia: Relationship between fibrosis and platelet-derived growth factor.

Acute megakaryoblastic leukaemia (AMGL) is an uncommon disease with poor prognosis. Histopathologically, AMGL cases show variable degree of fibrosis and the presence of uniform blasts or mature dysplastic megakaryocytes. Here we examined 18 cases of AMGL, including idiopathic (n = 9) and secondary (n = 9) cases. Fourteen cases were males and four were females, ranging in age from 14 to 87 years (median, 58). All cases had anaemia, but leukocyte and platelet counts varied. Blast cells were detected in the peripheral blood of 14 cases. Fourteen of 16 cases showed chromosomal abnormalities. The median survival was 6 months (range, 1-48 months). Survival rates did not correlate with the severity of fibrosis, proportion of blast cells and cause of AMGL. Nine of the 11 cases examined immunohistochemically were positive for platelet-derived growth factor (PDGF)(-BB), especially megakaryoblasts and a few fibroblasts. The PDGF-positive cases showed various degrees of fibrosis, while the negative cases showed no evidence of fibrosis. Our results confirmed the poor prognosis of patients with AMGL, irrespective of the degrees of fibrosis, and demonstrated that PDGF could play an important role in the pathogenesis of marrow fibrosis.

[A case of long-term survival after resection of metastatic lymph nodes along the superior mesenteric vein from early gastric cancer].

A 63-year-old man underwent distal gastrectomy and D1 + beta lymph node dissection for type II c early gastric cancer in the posterior wall of the antrum. In the fifth postoperative month, a mass appeared in the epigastric region, and serum tumor marker levels rose. Abdominal CT revealed a 4-cm mass anterior to the superior mesenteric vein. He was diagnosed with recurrence in the lymph nodes along the superior mesenteric vein (No. 14v). Since there was no evidence of recurrence elsewhere, the patient underwent resection of the lymph nodes and transverse colectomy, followed by five courses of chemotherapy with S-1 + cisplatin. At present, more than 38 months after surgery, he is alive without recurrence. Generally, chemotherapy is the first-line treatment for recurrent gastric cancer; however, surgery appears to be a treatment option if the tumor is localized and resectable.

Three-dimensional mapping of cardiac arrhythmias - string of pearls - .

The evolution of 3-dimensional (D) mapping systems has contributed to improved procedures for ablation of complex tachyarrhythmia in terms of providing detailed anatomical information along with the ability to integrate with pre-acquired computed tomography/magnetic resonance imaging/intracardiac echocardiography images, reducing the radiation exposure, and producing activation and substrate maps. 3-D mapping systems are categorized as magnetic based vs. impedance based according to the catheter location technology, and are also classified as contact based vs. non-contact based according to the data collection technology. Contact-based mapping systems are used widely, in which a series of electrograms is taken sequentially in contact with the heart, thus requiring a relatively stable and sustained arrhythmia to create an activation map. Non-contact mapping systems, however, allow a beat-to-beat analysis of the activation even in non-sustained, polymorphic, or hemodynamically intolerant tachycardia. In this article, the clinical utility of 3-D mapping systems is discussed based on the literature and on experience, with particular emphasis on the non-contact mapping system.

Synthesis, structural transformation, thermal stability, valence state, and magnetic and electronic properties of PbNiO3 with perovskite- and LiNbO3-type structures.

We synthesized two high-pressure polymorphs PbNiO(3) with different structures, a perovskite-type and a LiNbO(3)-type structure, and investigated their formation behavior, detailed structure, structural transformation, thermal stability, valence state of cations, and magnetic and electronic properties. A perovskite-type PbNiO(3) synthesized at 800 °C under a pressure of 3 GPa crystallizes as an orthorhombic GdFeO(3)-type structure with a space group Pnma. The reaction under high pressure was monitored by an in situ energy dispersive X-ray diffraction experiment, which revealed that a perovskit-type phase was formed even at 400 °C under 3 GPa. The obtained perovskite-type phase irreversibly transforms to a LiNbO(3)-type phase with an acentric space group R3c by heat treatment at ambient pressure. The Rietveld structural refinement using synchrotron X-ray diffraction data and the XPS measurement for both the perovskite- and the LiNbO(3)-type phases reveal that both phases possess the valence state of Pb(4+)Ni(2+)O(3). Perovskite-type PbNiO(3) is the first example of the Pb(4+)M(2+)O(3) series, and the first example of the perovskite containing a tetravalent A-site cation without lone pair electrons. The magnetic susceptibility measurement shows that the perovskite- and LiNbO(3)-type PbNiO(3) undergo antiferromagnetic transition at 225 and 205 K, respectively. Both the perovskite- and LiNbO(3)-type phases exhibit semiconducting behavior.

An approach to control of band gap energy and photoluminescence upon band gap excitation in Pr(3+)-doped perovskites La(1/3)MO3 (M=Nb, Ta):Pr3+.

We synthesized polycrystalline pristine and Pr(3+)-doped perovskites La(1/3)MO(3) (M = Nb, Ta):Pr(3+) and investigated their crystal structure, optical absorption, and luminescence properties. The optical band gap of La(1/3)NbO(3) (3.2 eV) is smaller than that of La(1/3)TaO(3) (3.9 eV), which is primarily due to the difference in electronegativity between Nb and Ta. In La(1/3)NbO(3):Pr(3+), the red emission assigned to the f-f transition of Pr(3+) from the excited (1)D(2) level to the ground (3)H(4) state upon band gap photoexcitation (near-UV) was observed, whereas the f-f transition of Pr(3+) with blue-green emission from the excited (3)P(0) level to the ground (3)H(4) state was quenched. On the other hand, in La(1/3)TaO(3):Pr(3+), the blue-green emission upon band gap photoexcitation was observed. Their differences in emission behavior are attributed to the energy level of the ground and excited states of 4f(2) for Pr(3+), relative to the energy levels of the conduction and valence bands, and the trapped electron state, which mediates the relaxation of electron from the conduction band to the excited state of Pr(3+). La(1/3)NbO(3):Pr(3+) is a candidate red phosphor utilizing near-UV LED chips (e.g., λ = 375 nm) as an excitation source.

Atrial tachycardia during ongoing atrial fibrillation ablation. - EnSite array analysis-.

BACKGROUND: Atrial tachycardia (AT) occurring during atrial fibrillation (AF) ablation is sometimes difficult to identify and eliminate. EnSite Array (EA) visualizes beat-to-beat virtual activation of AT. The aim of the present study was to characterize AT occurring during AF ablation during ongoing AF, using EA. METHODS AND RESULTS: Among 90 patients with AF (paroxysmal, n=67; persistent, n=23) who underwent radiofrequency catheter ablation during ongoing AF, 33 (37%) had 46 ATs that developed during ablation, and 9 (10%) of these patients had 9 ATs that developed before ablation. AT was sustained in 39 and non-sustained in 7. Nineteen ATs resulted from a focal mechanism and 27 from macroreentry. The major AT foci were distributed in the pulmonary vein (n = 8) and left atrial roof (n = 3), and macroreentrant ATs mainly consisted of peri-mitral AT (n = 10), common atrial flutter (n = 10), and roof reentrant AT (n = 3). After EA-guided ablation of AT, 41 ATs in 28 patients (85%) were eventually rendered non-inducible. During 21 ± 8 months of follow-up, 30 of the 33 patients (91%) were free from AF/AT recurrence. CONCLUSIONS: AT occurred in 37% of the patients during ongoing AF ablation, resulting from a focal or reentrant mechanism in diverse locations. Peri-mitral AT, common atrial flutter, and AT from the pulmonary vein were frequently observed. These ATs were eliminated by EA-guided radiofrequency ablation in most cases.

A new method of a pulmonary vein map to identify a conduction gap on the pulmonary vein antrum ablation line.

BACKGROUND: Electrical isolation of the pulmonary veins (PV) is crucial for atrial fibrillation (AF) ablation. Conduction gaps on the circumferential PV antrum ablation (CPVA) line sometimes remain, which are sometimes difficult to identify. METHODS AND RESULTS: CPVA of the ipsilateral superior and inferior PVs was performed during sinus rhythm or coronary sinus pacing using the NavX system in 22 AF patients, in whom 1 round of CPVA failed to disconnect 26 individual PVs (30%) in 18 patients. In these patients, a local activation map within the CPVA line (PV map) was created by a 20-pole circular mapping catheter with the use of the NavX, with 71 ± 37 sampling points per PV antrum. The conduction gap was defined as a site on the CPVA line, from which the activation proceeded toward the entire PV. The mapped PV antra were comprised of the left superior PV in 11, right superior PV in 10, left inferior PV in 3, right inferior PV in 1 and a left common PV in 1 PV(s). The conduction gaps were identified at 1.4 ± 0.7 sites per PV antrum, with an electrogram amplitude of 0.8 ± 0.7 mV. A point ablation at the gap completely isolated 24 out of 26 PV antra (92%) with 1.9 ± 1.3 applications. CONCLUSIONS: The PV map was useful for quickly and accurately identifying the conduction gap(s) after 1 round of CPVA.

Id1/Id3 knockdown inhibits metastatic potential of pancreatic cancer.

BACKGROUND: The Id (inhibitor of DNA binding/differentiation) proteins belong to the helix-loop-helix transcriptional regulatory factors, and play important roles in tumor development. Previously, we and others have shown that targeting Id in tumor cells could have important clinical implications. In the present study, we aimed to evaluate the effects of Id inhibition in human pancreatic cancer cells. MATERIALS AND METHODS: Id1 and Id3 were stably double-knockdown in human pancreatic cancer cell line MIA-Paca2 by means of RNA interference. Expression of Id and integrins were analyzed by flow-cytometry. Cell proliferation was evaluated by MTS assay. Migration was measured by wound closure assay. Adhesion assay was performed to evaluate binding capacity for different extracellular matrix proteins. Finally, in vivo properties of tumor cells were observed in a mouse model of peritoneal metastasis. RESULTS: Id1/Id3 double-knockdown resulted in decreased ability of pancreatic cancer cells to proliferate and migrate. In addition, Id1/Id3 double-knockdown caused decreased expression of integrins alpha3, alpha6, and beta1, and consequently reduced adhesion of tumor cells to laminin. Finally, peritoneal metastases of Id1/Id3 double-knockdown tumor cells were significantly reduced. CONCLUSIONS: We concluded that the Id proteins play a pivotal role in the development of peritoneal metastasis of pancreatic cancer, and consequently, their targeting would be a novel strategy for the prevention and treatment of pancreatic cancer.

Characterization of non-pulmonary vein foci with an EnSite array in patients with paroxysmal atrial fibrillation.

AIMS: Non-pulmonary vein (PV) foci are sometimes difficult to identify and eliminate. The EnSite array (EA) reveals the detailed beat-to-beat virtual activation. This study aimed to characterize non-PV foci using the EA. METHODS AND RESULTS: Sixty-five patients with paroxysmal atrial fibrillation (AF) were included. All had ectopy initiating AF and/or focal atrial tachycardia analysed using the EA. All patients underwent PV isolation (PVI) and additional ablation of non-PV foci if present. The EA revealed 59 PV foci in 48 patients (Group P) and 19 non-PV foci in 17 patients (Group N). In Group N, 12 patients (71%) also had 17 PV foci. The non-PV foci were frequently distributed in the left atrial (LA) roof (n = 5) and superior vena cava (n = 5). Pulmonary vein isolation during on-going AF terminated AF in 34 of 37 in Group P (92%) and 4 of 14 in Group N (29%) patients (P < 0.0001). All non-PV foci were eliminated by an EA-guided ablation. During a 23 ± 10 month follow-up, 11 patients (17%) had AF recurrences, mainly due to LA-PV reconnection. CONCLUSION: Non-PV foci are prevalent in the LA roof and SVC sites, but can originate from other sites as well. When non-PV foci are observed, PVI may be insufficient and should be supplemented with non-PV foci ablation.

Characterization of bipolar electrograms during sinus rhythm for complex fractionated atrial electrograms recorded in patients with paroxysmal and persistent atrial fibrillation.

AIMS: Complex fractionated atrial electrogram (CFAE) has been reported to relate to maintain atrial fibrillation (AF). The aims of this study were to investigate the relationship between CFAE and background conditions during sinus rhythm (SR). METHODS AND RESULTS: Electroanatomical mapping using an EnSite Array was performed in 20 patients (paroxysmal AF:persistent AF = 16:4) who underwent pulmonary vein antrum isolation (PVAI). Contact bipolar electrograms were recorded before PVAI, during SR, and subsequently during induced AF. Peak-to-peak voltages and morphologies of the electrograms during SR were compared between sites with and without CFAE during AF. Among 1947 points obtained during SR, 974 (50%) were included in CFAE sites and 973 (50%) in non-CFAE sites. Electrogram amplitude during SR was higher at the CFAE sites than at the non-CFAE sites (2.4 +/- 1.7 vs. 1.9 +/- 1.9 mV; P < 0.0001), whereas fractionated or double electrograms were found in a similar range between the two areas (2 vs. 3%; P = 0.21). When analysed further in terms of AF termination by PVAI followed by confirmation of non-inducibility, the voltage of electrograms at the CFAE sites was lower (2.1 +/- 1.7 vs. 2.6 +/- 1.8 mV; P = 0.0001) and the morphology was more complex in patients without AF termination compared with those with AF termination. CONCLUSION: Our results suggest that in paroxysmal and persistent AF with minimally damaged LA, the CFAE sites in patients with AF termination by PVAI alone represent healthy atrial tissue with rapid electrical activity in response to an AF driver located in the pulmonary vein. However, in patients without AF termination, they represent more damaged tissue responsible for maintaining AF.