Transcriptional Active Parvovirus B19 Infection Predicts Adverse Long-Term Outcome in Patients with Non-Ischemic Cardiomyopathy

Parvovirus B19 (B19V) is the predominant cardiotropic virus currently found in endomyocardial biopsies (EMBs). However, direct evidence showing a causal relationship between B19V and progression of inflammatory cardiomyopathy are still missing. The aim of this study was to analyze the impact of transcriptionally active cardiotropic B19V infection determined by viral RNA expression upon long-term outcomes in a large cohort of adult patients with non-ischemic cardiomyopathy in a retrospective analysis from a prospective observational cohort. In total, the analyzed study group comprised 871 consecutive B19V-positive patients (mean age 50.0 ± 15.0 years) with non-ischemic cardiomyopathy who underwent EMB. B19V-positivity was ascertained by routine diagnosis of viral genomes in EMBs. Molecular analysis of EMB revealed positive B19V transcriptional activity in n = 165 patients (18.9%). Primary endpoint was all-cause mortality in the overall cohort. The patients were followed up to 60 months. On the Cox regression analysis, B19V transcriptional activity was predictive of a worse prognosis compared to those without actively replicating B19V (p = 0.01). Moreover, multivariable analysis revealed transcriptional active B19V combined with inflammation [hazard ratio 4.013, 95% confidence interval 1.515–10.629 (p = 0.005)] as the strongest predictor of impaired survival even after adjustment for age and baseline LVEF (p = 0.005) and independently of viral load. The study demonstrates for the first time the pathogenic clinical importance of B19V with transcriptional activity in a large cohort of patients. Transcriptionally active B19V infection is an unfavourable prognostic trigger of adverse outcome. Our findings are of high clinical relevance, indicating that advanced diagnostic differentiation of B19V positive patients is of high prognostic importance.

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Impact of tricuspid valve regurgitation severity and its secondary reduction on long-term survival after transcatheter mitral valve edge-to-edge repair

European Heart Journal ◽

10.1093/ehjci/ehaa946.2634 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Geyer ◽

K Keller ◽

T Ruf ◽

F Kreidel ◽

A Petrescu ◽

...

Keyword(s):

Mitral Valve ◽

Cox Regression ◽

Valve Regurgitation ◽

Term Survival ◽

Long Term Outcome ◽

Long Term Survival ◽

Cox Regression Analysis ◽

The Impact

Abstract Background Mitral valve regurgitation (MR) is a frequent heart valve disorder affecting 1–2% of the humans in the general population and over 10% of the individuals older than 75 years. While a symptomatic and prognostic benefit of transcatheter edge-to-edge repair for MR (TMVR) was reported, data regarding long-term outcome as well as influence of concomitant tricuspid regurgitation (TR) are sparse. Purpose We aimed to investigate the impact of periinterventional development of TR on survival of patients undergoing interventional edge-to-edge repair for MR in a large retrospective monocentric study. Methods We retrospectively analyzed survival of patients successfully treated with isolated edge-to-edge repair for MR from 06/2010–03/2018 (exclusion of combined forms of TMVR) in our center. Baseline, periprocedural as well as follow-up data were gathered. Concomitant TR was evaluated at baseline and after 30 days and categorized from grades 0 (no TR) to grade III (severe TR). We analyzed the influence of severe vs. non-severe TR on 30-day, 1-year and long-term survival. Results Overall, 627 consecutive patients (47.0% female, 57.4% functional MR) were enrolled. Median follow-up time was 462 days [IQR 142–945]. Survival status was available in 96.7%. Survival rates were 97.6% at discharge, 75.7% after 1, 54.5% after 3, 37.6% after 5 and 21.7% after 7 years. TR at baseline (examination results were available in 92.3%) was categorized as severe TR in 25.6%, medium TR in 33.3%, mild TR in 35.1% and no TR in 6.0%. TR at 1 month (examination results were available in 81.1%) was severe in 16.7%, medium in 30.2%, mild in 45.6% and no TR was found in 7.4%; improvement by at least 1 TR-grade was documented in 33.6% of the patients. While a severe (compared to non-severe) TR at baseline did not affect the 30-day mortality (7.4% vs. 5.2%, p=0.354), 1-year survival was substantially impaired in those patients (36.5% vs. 23.0%, p=0.012). Accordingly, severe TR was not associated with 30d-mortality (as evaluated by univariate Cox regression, p=0.340), but with 1-year survival (HR 1.78, 95% CI 1.19–2.65, p=0.005) and showed a trend towards impaired long-term survival (HR 1.30, 95% CI 0.96–1.76, p=0.089). While residual severe TR at one month did not influence 1-year-mortality significantly (p=0.478), improvement of TR demonstrated a trend to better survival after the first year (86.9 vs. 81.0%, p=0.208) confirmed in the Cox regression analysis (HR 0.66, 95% CI 0.36–1.22, p=0.188). Conclusions In this large retrospective monocentric study with a long-term follow-up-period of >7 years after edge-to-edge therapy for MR, we demonstrated that severe TR at the time of the intervention had an impact on 1-year-survival. Furthermore, a missing periinterventional improvement of TR was shown to be unfavorable regarding the long-term survival of these patients. Funding Acknowledgement Type of funding source: None

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Impact of Hybrid Operating Rooms on Long-Term Clinical Outcomes Following Fenestrated and Branched Endovascular Aortic Repair

Journal of Endovascular Therapy ◽

10.1177/1526602821996725 ◽

2021 ◽

pp. 152660282199672

Author(s):

Giovanni Tinelli ◽

Marie Bonnet ◽

Adrien Hertault ◽

Simona Sica ◽

Gian Luca Di Tanna ◽

...

Keyword(s):

Operating Room ◽

Clinical Outcomes ◽

Cox Regression ◽

Statistical Significance ◽

Aortic Aneurysms ◽

Study Patient ◽

Cox Regression Analysis ◽

Significant Difference ◽

The Impact

Purpose: Evaluate the impact of hybrid operating room (HOR) guidance on the long-term clinical outcomes following fenestrated and branched endovascular repair (F-BEVAR) for complex aortic aneurysms. Materials and Methods: Prospectively collected registry data were retrospectively analyzed to compare the procedural, short- and long-term outcomes of consecutive F-BEVAR performed from January 2010 to December 2014 under standard mobile C-arm versus hybrid room guidance in a high-volume aortic center. Results: A total of 262 consecutive patients, including 133 patients treated with a mobile C-arm equipped operating room and 129 with a HOR guidance, were enrolled in this study. Patient radiation exposure and contrast media volume were significantly reduced in the HOR group. Short-term clinical outcomes were improved despite higher case complexity in the HOR group, with no statistical significance. At a median follow-up of 63.3 months (Q1 33.4, Q3 75.9) in the C-arm group, and 44.9 months (Q1 25.1, Q3 53.5, p=0.53) in the HOR group, there was no statistically significant difference in terms of target vessel occlusion and limb occlusion. When the endograft involved 3 or more fenestrations and/or branches (complex F-BEVAR), graft instability (36% vs 25%, p=0.035), reintervention on target vessels (20% vs 11%, p=0.019) and total reintervention rates (24% vs 15%, p=0.032) were significantly reduced in the HOR group. The multivariable Cox regression analysis did not show statistically significant differences for long-term death and aortic-related death between the 2 groups. Conclusion: Our study suggests that better long-term clinical outcomes could be observed when performing complex F-BEVAR in the latest generation HOR.

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Long-term success of flexible endoscopic septal division with the stag beetle knife for Zenker’s diverticulum: a tertiary center study

Diseases of the Esophagus ◽

10.1093/dote/doaa019 ◽

2020 ◽

Vol 33 (11) ◽

Author(s):

Sauid Ishaq ◽

Keith Siau ◽

Minhong Lee ◽

Haleema Sultan ◽

Shalmani H Mohaghegh ◽

...

Keyword(s):

Cox Regression ◽

Multivariable Analysis ◽

Zenker’S Diverticulum ◽

Long Term Outcome ◽

Zenker's Diverticulum ◽

Tertiary Center ◽

Symptom Remission ◽

Treatment Naïve ◽

Symptom Recurrence

Summary Objectives Flexible endoscopic septum division is an established treatment for Zenker’s diverticulum (ZD); however, long-term outcome data are lacking. We aimed to evaluate the long-term efficacy of flexible endoscopic septal division (FESD) using the stag beetle knife for ZD and identify predictors of symptom recurrence. Methods Patients undergoing the procedure between 2013 and 2018 were prospectively enrolled. Procedures were performed by a single operator. Symptom severity pre- and postprocedure was recorded using the dysphagia, regurgitation, and complications scale. Symptom recurrence was defined as a total score > 1 after the index procedure. Time-to-event analyses were performed using Kaplan–Meier plots, with multivariable analyses performed using Cox regression models. Results Altogether, 65 patients (mean age 74.0 years, 60% male) were included. Previous stapling had been performed in 44.6% of patients. Over the mean posttreatment follow-up period of 19 months, 5.6% of the treatment naïve group and 34.5% of the recurrent group underwent repeated FESD (P = 0.003), with rates of symptom remission and improvement of 75.4% and 92.7%, respectively. Recurrence at 48 months was higher in patients with recurrent ZD (84.7%) than in treatment-naïve patients (10.7%). On multivariable analysis, recurrent disease (hazard ratio [HR] 20.8, P = 0.005) and younger age (HR 0.96/year, P = 0.047) were associated with symptom recurrence. Conclusions In patients with treatment-naïve ZD, flexible endoscopic septal division is safe and provides durable symptom remission. However, in patients with poststapling recurrence, the risk of recurrence is high and time-dependent.

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Clinicopathological Features of Remnant Gastric Cancer After Gastrectomy

The American Surgeon ◽

10.1177/00031348211056281 ◽

2021 ◽

pp. 000313482110562

Author(s):

Kenichi Iwasaki ◽

Edward Barroga ◽

Yota Shimoda ◽

Masaya Enomoto ◽

Erika Yamada ◽

...

Keyword(s):

Medical Records ◽

Tumor Invasion ◽

Cox Regression ◽

Remnant Stomach ◽

Invasion Depth ◽

Term Outcome ◽

Long Term Outcome ◽

Cox Regression Analysis ◽

Tumor Invasion Depth

Background Remnant gastric cancer (RGC) encompasses all cancers arising from the remnant stomach. Various studies have reported on RGC and its prognosis, but no consensus on its surgical treatment and postoperative management has been reached. Moreover, the correlation between the clinicopathological characteristics and long-term outcomes of RGC remains unclear. This study investigated the clinicopathological factors associated with the long-term survival of RGC patients. Methods The medical records (March 1993-September 2020) of 104 RGC patients from Tokyo Medical University Hospital database were analyzed. Of these 104 patients, the medical records of 63 patients who underwent surgical curative resection were analyzed using R. Kaplan-Meier plots of cumulative incidence of RGC were made. Differences in survival rates were compared using the log-rank test. Prognostic factors were analyzed using multivariate Cox regression analysis ( P < .05). Results Of the 104 RGC patients, 63 underwent total remnant stomach excision. The median time from the first surgery to the total excision was 10 years. The 5-year survival rate of the 63 RGC patients was .55 ((95% CI); .417-.671). The clinicopathological factors that were significantly associated with the long-term outcome of the RGC patients were tumor diameter (≥3.5 cm), presence or absence of combined resection of multiple organs, tumor invasion (deeper than T2), TNM stage, and postoperative morbidity. The multivariate Cox regression analysis showed that tumor invasion depth was the only independent prognostic factor for RGC patients [HR (95% CI): 5.49 (2.629-11.5), P ≤ .005]. Conclusions Among prognostic factors, tumor invasion depth was the only independent factor affecting RGC’s long-term outcome.

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Prognostic factors in the persistence of posttraumatic epilepsy after penetrating head injuries sustained in war

Journal of Neurosurgery ◽

10.3171/2008.4.17519 ◽

2009 ◽

Vol 110 (2) ◽

pp. 319-326 ◽

Cited By ~ 24

Author(s):

Behzad Eftekhar ◽

Mohammad Ali Sahraian ◽

Banafsheh Nouralishahi ◽

Ali Khaji ◽

Zahra Vahabi ◽

...

Keyword(s):

Prognostic Factors ◽

Cox Regression ◽

Head Injuries ◽

Clinical Findings ◽

Term Outcome ◽

Long Term Outcome ◽

Cox Regression Analysis ◽

Posttraumatic Epilepsy ◽

Kaplan Meier

Object The goal of this paper was to investigate the long-term outcome and the possible prognostic factors that might have influenced the persistence of posttraumatic epilepsy after penetrating head injuries sustained during the Iraq–Iran war (1980–1988). Methods In this retrospective study, the authors evaluated 189 patients who sustained penetrating head injury and suffered posttraumatic epilepsy during the Iraq–Iran war (mean 18.6 ± 4.7 years after injury). The probabilities of persistent seizures (seizure occurrence in the past 2 years) in different periods after injury were estimated using the Kaplan-Meier method. The possible prognostic factors (patients and injury characteristics, clinical findings, and seizure characteristics) were studied using log-rank and Cox regression analysis. Results The probability of persistent seizures was 86.4% after 16 years and 74.7% after 21 years. In patients with < 3 pieces of shrapnel or no sphincter disturbances during seizure attacks, the probability of being seizure free after these 16 and 21 years was significantly higher. Conclusions Early seizures, prophylactic antiepileptics drugs, and surgical intervention did not significantly affect long-term outcome in regard to persistence of seizures.

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Dissecting outcomes of patients (pts) with

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5043 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5043-5043

Author(s):

Praful Ravi ◽

Gregory Russell Pond ◽

Leonidas Nikolaos Diamantopoulos ◽

Rohit K. Jain ◽

William Paul Skelton ◽

...

Keyword(s):

Urinary Tract ◽

Cox Regression ◽

Pathologic Complete Response ◽

Multivariable Analysis ◽

Pathologic Response ◽

Cox Regression Analysis ◽

Risk Of Recurrence ◽

Split Dose ◽

Female Sex ◽

The Impact

5043 Background: Pathologic complete response (pCR) after NAC for MIBC is strongly correlated with long-term overall survival. However, there are sparse data on the risk of recurrence based on depth of pathologic response (pT0, pTa, pTis, pT1), and the differential impact of clinicopathologic factors and NAC regimen on recurrence. Methods: Baseline data on all pts with cT2-4N0-1 MIBC receiving NAC and who achieved < ypT2N0 disease at radical cystectomy (RC) from 9 international centers were obtained. The key outcome was time to recurrence (TTR) – defined as the time to any recurrence in the urinary tract or regional/distant metastasis, with death (in the absence of recurrence) considered a competing risk. Cox regression analysis was used to analyze the impact of clinical factors on recurrence. Results: A total of 506 pts were available. Median age was 66 years (range 33-86) and 78% (n = 396) were male; median follow-up after RC was 2.6 years. The majority of patients had pure urothelial histology (n = 371, 73%), and baseline stage was cT2N0 (n = 368, 73%), cT3-4N0 (n = 95, 19%) and TanyN1 (n = 43, 9%). NAC regimens were gemcitabine-cisplatin (GC, n = 296, 59%), dose-dense methotrexate-vinblastine-doxorubicin-cisplatin (ddMVAC, n = 141, 28%), split-dose GC (n = 29, 6%), MVAC (n = 29, 6%) and non-cisplatin based regimens (n = 11, 2%). At RC, 304 patients (60%) had ypT0N0 disease, 32 (6%) had ypTaN0, 107 (21%) had ypTisN0 and 63 (13%) had ypT1N0. Overall, 43 patients (8%) recurred with a median TTR of 56 weeks (range 7-251); 5-year freedom from recurrence was 87% (95% CI 83-91). The majority (n = 38) recurred outside the urinary tract. On multivariable analysis, ypTa (HR = 3.36 [1.24-9.11]) and ypT1 (HR = 2.88 [1.33-6.22], p = 0.013) disease at RC were predictors of shorter TTR, while female sex was associated with longer TTR (HR = 0.52 [0.27-0.98], p = 0.043). The type of NAC was not predictive of TTR (GC vs. other, HR = 1.49 [0.75-2.97], p = 0.26). Conclusions: To our knowledge, this is the largest study to quantify the risk of recurrence in pts achieving pathologic response after NAC and RC for MIBC. 8% of patients undergoing NAC and achieving < ypT2N0 at RC recurred. Residual ypTa and ypT1 disease conferred a significantly higher risk of recurrence, while ypTis did not; female sex was associated with a lower risk of recurrence. Importantly, the type of cisplatin-based NAC regimen used was not an independent predictor of recurrence.

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Long Term Outcome Prediction in Stemi/Nstemi Patients By Means of the Model Consisting of Simple Clinical Parameters

Emergency Medical Service ◽

10.36740/emems202103101 ◽

2021 ◽

Vol 8 (3) ◽

pp. 159-170

Author(s):

Paweł Korczyc ◽

Jędrzej Chrzanowski ◽

Arkadiusz Stasiak ◽

Joanna Stasiak ◽

Andrzej Bissinger ◽

...

Keyword(s):

Regression Model ◽

Cox Regression ◽

Everyday Practice ◽

Syntax Score ◽

Clinical Parameters ◽

Observation Study ◽

Cox Regression Model ◽

Long Term Outcome ◽

The Impact

Aim: Our study aimed to identify the clinical variables associated with long-term mortality after MI and to construct a simple, easy to use clinical practice model for the prediction of 5 year mortality after MI. Material and Methods: This is a prospective 5-year observation study of MI patients admitted to the Department of Cardiology at the Copernicus Memorial Hospital in Lodz in 2010 and 2011. The data were collected during hospitalization and again after a period of 1 and 5 years. A multi-factor multi-level Cox regression model was constructed to investigate the impact of clinical factors on long-term survival.results: 92 patients (39 STEMI, 53 NSTEMI) were included in the study and their data were used to construct a Cox regression model with satisfactory fit (R 2 =0.7945). Factors associated with a decrease in 5-year risk are: age (1.06, 95%CI: 1.01-1.11), SYNTAX score (1.05, 95%CI: 1.02-1.08), WBC level (1.16, 95%CI: 1.08-1.26), and glycemia at enrollment (1.01, 95%CI: 1.01-1.01). Higher values of HDL at enrollment were associated with a decrease in 5-year risk (HR=0.97, 95%CI: 0.93-0.99).conclusion: The model we created is a valuable tool that is useful and easy to employ in everyday practice for assessing the 5-year prognosis of patients after MI. What is new: The study presents the new model for prediction of 5-year mortality after myocardial infarction. This model is based on simple clinical parameters and may by applied in everyday practice.

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Long term clinical impact of successful recanalization of chronic total occlusion in patients with and without type 2 diabetes mellitus

10.21203/rs.3.rs-28914/v1 ◽

2020 ◽

Author(s):

Chuan-Tsai Tsai ◽

Wei-Chieh Huang ◽

Hsin-I Teng ◽

Yi-Lin Tsai ◽

Tse-Min Lu

Keyword(s):

Diabetes Mellitus ◽

Cox Regression ◽

Total Occlusion ◽

Long Term Outcome ◽

Chronic Total Occlusions ◽

Cox Regression Analysis ◽

All Cause Mortality ◽

Diabetes Patients

Abstract Background Diabetes mellitus is one of the risk factors for coronary artery disease and frequently associated with multivessels disease and poor clinical outcomes. Long term outcome of successful revascularization of chronic total occlusions (CTO) in diabetes patients remains controversial. Methods and results From January 2005 to December 2015, 739 patients who underwent revascularization for CTO in Taipei Veterans General Hospital were included in this study, of which 313 (42%) patients were diabetes patients. Overall successful rate of revascularization was 619 (84%) patients whereas that in diabetics and non-diabetics were 265 (84%) and 354 (83%) respectively. Median follow up was 1095 days (median: 5 years, interquartile range: 1–10 years). During 3 years follow-up period, 59 (10%) in successful group and 18 (15%) patients in failure group died. Although successful revascularization of CTO was non-significantly associated with better outcome in total cohort (Hazard ratio (HR):0.593, 95% confidence interval (CI): 0.349–0.008, P:0.054), it might be associated with lower risk of all-cause mortality (HR: 0.307, 95% CI: 0.156–0.604, P: 0.001) and CV mortality (HR: 0.266, 95% CI: 0.095–0.748, P: 0.012) in diabetics (P: 0.512). In contrast, successful CTO revascularization didn’t improve outcomes in non-diabetics (all p > 0.05). In multivariate cox regression analysis, successful CTO revascularization remained an independent predictor for 3-years survival in diabetic subgroup (HR: 0.289, 95% CI: 0.125–0.667, P: 0.004). The multivariate analysis result was similar after propensity score matching (all-cause mortality, HR: 0.348, 95% CI: 0.142–0.851, P: 0.021). Conclusion Successful CTO revascularization was associated with reduced long term all-cause/cardiovascular mortality in diabetics but not in non-diabetic population.

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Multimodality treatment of non small cells lung cancer (NSCLC) brain metastases: Long term outcome

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17046 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17046-17046

Author(s):

A. Cassano ◽

A. Pompucci ◽

E. D’Argento ◽

G. Schinzari ◽

A. Di Chirico ◽

...

Keyword(s):

Lung Cancer ◽

Regression Analysis ◽

Brain Metastases ◽

Cox Regression ◽

Radical Surgery ◽

Therapeutic Option ◽

Term Outcome ◽

Long Term Outcome ◽

Cox Regression Analysis

17046 Background: Lung cancer is the most common cause of cancer deaths and has the highest incidence for brain metastases of all malignancies. The prognosis of these patients (pts) remain poor with a median survival of 4–5 months. Whole brain radiation therapy (WBRT) in inoperable brain metastases prolongs survival to 3–5 months. In pts with 1 or ≤ 3 brain metastases neurosurgical resection improves median survival to 3.5–8 months. The aim of this study was to evaluate the long-term outcome of patients with brain metastases from NSCLC treated with multimodal strategy, including systemic chemotherapy, neurosurgery and radiotherapy. Methods: From 1997 to 2005, 56 pts were considered. Inclusion criteria were: single or multiple NSCLC brain metastases suitable of surgery; Karnofsky performance status ≥ 70%; controlled extracranial disease with Cisplatin-based chemotherapy; life expectancy > 4 months. Surgery was followed by 40 Gy WBRT. Statistical analysis was performed using the Kaplan-Meier method and Cox-regression analysis. Results: The median age was 58.4 years. The histological types were adenocarcinoma in 35 pts (62.5%), squamous cell carcinoma in 11 pts (19.7%) and large cell carcinoma in 10 pts (17.8%). The lesions were single in 39/56 pts (69.6%) and multiple in the other pts (30.4%). Radical surgery was performed in 37 pts (66%), while surgical citoreduction was possible in 19 pts (34%). The median follow-up period was 22.12 months (range 2–90 months). Overall survival (OS) of the whole group was 12.8 months; OS of pts radically resected was 16.5 months while OS of pts partially resected was 7.2 months. Based on Cox-regression analysis, age < 65 years and radical resection were independent predictors of survival (respectively p = 0.004–95% CI 1.46–7.6 and p = 0.04–95% CI 1.03–4.97), while the number of lesions was not relevant in terms of OS. Conclusions: Analysis of long-term outcome seems to confirm that the combined treatment of NSCLC brain metastases is a primary therapeutic option. In our series of 56 patients, radical surgery, not the number of metastases, was related with prolonged survival. Further randomized studies comparing surgery+WBRT vs gamma-knife-radiosurgery could define the best therapeutic option in the different subsets of pts. No significant financial relationships to disclose.

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Correlation of high density of CD8+and FoxP3+ lymphocytes with overall survival in intestinal-type periampullary adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.266 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 266-266

Author(s):

Carl Fredrik Warfvinge ◽

Jacob Elebro ◽

Margareta Heby ◽

Bjorn Nodin ◽

Jakob Eberhard ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Multivariable Analysis ◽

High Density ◽

Intestinal Type ◽

Periampullary Cancer ◽

Type I ◽

Cox Regression Analysis ◽

Periampullary Adenocarcinoma ◽

The Impact

266 Background: Periampullary cancers can be divided into different morphological subtypes where those having an intestinal-type (I-type) morphology have a better prognosis than those with a pancreatobiliary-type (PB-type) morphology. In recent years much focus of antineoplastic research has been directed towards the central role played by various subsets of T-lymphocytes. Yet, very little is known of their role in different subtypes of periampullary cancer. Therefore, the aim of this study was to analyze the density of CD8+ (cytotoxic) and FoxP3+ (regulatory) T-cells in periampullary cancer, with particular reference to their relationship with survival by morphological subtype. Methods: Immunohistochemical expression of CD8 and FoxP3-positive tumor-infiltrating lymphocytes (TILs) was analyzed in tissue microarrays with tumors from 175 consecutive cases of periampullary adenocarcinoma, 110 of PB-type and 65 of I-type morphology, treated with pancreaticoduodenectomy. Kaplan-Meier and univariable and multivariable Cox regression analysis, adjusted for age, T-stage, N-stage, grade, sex, invasion of blood vessels, lymphatic vessels, adjuvant chemotherapy and resection margins were applied to determine the impact of CD8 and FoxP3 expression on 5-year overall survival (OS). Results: In I-type tumors, a high density of CD8+ as well as FoxP3+ TILs was significantly associated with a prolonged overall survival (HR = 0.39, 95% CI 0.19-0.80 and HR = 0.32, 95% CI 0.15 –0.67). The association between high density of FoxP3+ TILs and survival remained significant in multivariable analysis (HR = 0.37, 95% CI 0.17-0.84) while the association between CD8+ TILs and survival did not. The density of CD8+ and FoxP3+ TILs was not prognostic in PB-type tumors. Conclusions: High density of CD8+ and FoxP3+ TILs correlates with a prolonged overall survival in I-type but not in PB-type periampullary adenocarcinomas. Thus, morphological subtype appears to be an important determinant of the prognostic and predictive impact of the inflammatory microenvironment in periampullary carcinoma, and should be considered in future studies.

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