The absence of real-time pulmonary vein isolation during cryoballoon ablation is associated with atrial fibrillation recurrence and pulmonary vein reconnection : Insights from the Middelheim-PVI Registry 2.

BACKGROUND: Absence of real-time pulmonary vein (PV) isolation (PVI) occurring in 15-40% of PVs during cryoballoon ablation (CBA) of atrial fibrillation (AF) raises doubt about adequate PVI. Aim of the present study is to determine whether real-time PVI during CBA is predictive of long-term clinical outcome and durability of PVI. METHODS: Eight hundred three AF patients (64 ± 10 years, 68% males) undergoing CBA were studied. The cohort was divided in 4 groups according to the number of PVs without real-time PVI: none (N = 252 [31.4%]), 1 (N = 255 [31.8%]), 2 (N = 159 [19.8%]), and 3-4 (N = 137 [17.1]). RESULTS: At 3 years, 279 (34.7%) patients had recurrence of AF of which 188 underwent repeat ablation. A vein without real-time PVI was associated with AF recurrence (HR = 1.275; 95% CI 1.134-1.433; p < 0.01), independent of persistent AF type (HR = 2.075; 95% CI 1.584-2.738; p < 0.01), left atrial diameter (HR = 1.050; 95% CI 1.028-1.072; p < 0.01), and diagnosis-to-ablation time (HR = 1.002; 95% CI 1.000-1.005; p = 0.04). Highest success was achieved with present real-time PVI in all veins (77.4%), gradually decreasing per increasing number of absent real-time PVI: 66.3% for 1 vein, 58.5% for 2, and 48.9% for 3-4 veins (p < 0.001). At repeat ablation (N = 188), PV reconnection was seen in 99/430 (23.0%) versus 83/288 (28.8%) veins with and without real-time PVI, respectively (p = 0.08). Right inferior PVs (RIPVs) with real-time PVI were less reconnected than RIPVs without real-time PVI: 29.7% versus 43.7% (p = 0.047). CONCLUSION: The absence of real-time PVI during CBA independently predicts AF recurrence with a 30% gradual decrease in outcome per increase in veins without real-time PVI. Real-time PVI is particularly important for the RIPV to achieve durable PVI.

Relationship between tumor-associated immune infiltrate and p16 staining over clinicopathological features in acral lentiginous melanoma.

PURPOSE: This study aims to evaluate the association between composition of tumor-infiltrating lymphocytes (TIL) and expression of p16 in acral lentiginous melanoma (ALM), and their impact on prognosis. MATERIALS AND METHODS: A cohort of 148 surgical pathology specimens of ALM was studied. TIL were evaluated by immunohistochemical detection of CD3 and CD8, along with CD20, CD4, CD68, and CD163 in a subset of 43 cases. p16 protein expression was also investigated in all the cases. RESULTS: The median age was 66 years, median Breslow thickness was 6.0 mm, grade III TIL was found in 28.4% and lymph nodes were involved in 54.2%. Breslow thickness (p < 0.001), stage I-II (p < 0.001), negative lymph nodes (p < 0.001) and < 10% p16 (p = 0.01) were associated with longer survival. Grade III of TIL was associated with thinner Breslow thickness (p = 0.008) and lower mitosis (p = 0.047). A higher density of CD3 TIL was associated with male gender (p = 0.008), thinner Breslow thickness (p = 0.047), negative lymph node (p = 0.031), early stage (p = 0.046), and p16 nuclear expression of > 10% (p = 0.045). Higher CD8 TIL was associated with > p16 (p = 0.03). Survival analysis found that longer survival had a trend to be associated with high TIL (p = 0.090). Levels of CD3+ and CD8+ cells were correlated with those of CD4+, CD20+, CD68+ and CD163+ immune cells. CONCLUSIONS: Higher levels of TIL tend to be associated with better overall survival in ALM. Loss of expression of p16 is associated with lower levels of CD3+ and CD8+ TIL, indicating a probable relationship between p16 and TIL immune response in ALM .

Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America

Purpose. Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome. Methods. All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed. Results. 537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I-II patients had a median OS of 5.3 (95% CI 4.3-6.2) for ALM and 9.2 (95% CI 5.0-7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001). Conclusions. ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM (AU)

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Tumor infiltrating lymphocytes in acral lentiginous melanoma: a study of a large cohort of cases from Latin America.

PURPOSE: Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome. METHODS: All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified. Clinicopathological information was obtained from the medical charts. A prospective evaluation of TIL was performed. Analysis of association between ALM and clinicopathological features including TIL as well as survival analysis compared the outcome of ALM to whole group and extremity NALM was performed. RESULTS: 537 ALM from a total of 824 cutaneous melanoma cases were studied. Older age (p = 0.022), higher Breslow (p = 0.008) and ulceration (p < 0.001) were found to be more frequent in ALM. Acral had worse overall survival (OS) compared with the whole group (p = 0.04). Clinical stage (CS) I-II patients had a median OS of 5.3 (95% CI 4.3-6.2) for ALM and 9.2 (95% CI 5.0-7.0) for extremity NALM (p = 0.016). Grade 0 (absence of TIL), I, II and III were found in 7.5, 34.5, 32.1, and 25.9%, respectively. Lower TIL grade was associated with larger tumor size (p = 0.003), higher Breslow (p = 0.001), higher Clark level (p = 0.007), higher CS (p = 0.002), extremity location (p = 0.048), histological subtype ALM (p = 0.024) and better OS (p = 0.001). CONCLUSIONS: ALM is highly prevalent in Peru and carries poor outcome. Lower TIL levels were associated with poor outcome and ALM.

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru.

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation-positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer.

Absence of infection with human immunodeficiency virus in Peruvian prostitutes.

We serologically tested 140 female prostitutes (mean age, 30 years) from the port city of Callao, Peru, for evidence of infection with human immunodeficiency virus (HIV), Chlamydia trachomatis, Treponema pallidum, herpes simplex viruses (HSV) I and II, and hepatitis B virus. The women had worked as prostitutes for an average of 5 years; one-fourth serviced foreign visitors exclusively, mainly sailors. Only 4 women used condoms, and only 1 woman gave a history of parenteral narcotic abuse, although 53% were regularly exposed to unsterile needles outside the medical setting for injections of vitamins, antibiotics, or steroids; another 29% are thought to probably use unsterile needles. None of the 140 prostitutes screened was seropositive for HIV, despite a very high prevalence of antibody to T. pallidum (24%), C. trachomatis (97%), HSV I and II (100%), and hepatitis B (51%); 5% were HbsAg positive. These data indicate that HIV has not yet been introduced into female prostitutes in the Peruvian port city. We believe that widespread use of unsterile needles in developing countries, such as Peru, represents a serious health threat and will amplify the spread of HIV, once introduced.