Natural course of chronic pancreatitis and predictors of its progression

BackgroundThe natural course of chronic pancreatitis(CP) and its complications has been inadequately explored. We aimed to describe the natural history and factors affecting the progression of alcoholic(ACP), idiopathic juvenile(IJCP) and idiopathic senile(ISCP) variants of CP.MethodsThis study was a retrospective analysis from a prospectively maintained database of patients with CP following up at a tertiary care centre from 1998 to 2019. Cumulative rates of pain resolution, diabetes, steatorrhea, pseudocysts and pancreatic cancer were computed using Kaplan-Meier analysis, and the factors affecting their incidence were identified on multivariable-adjusted Cox-proportional-hazards model.ResultsA total of 1415 patients were included, with 540(38.1%) ACP, 668(47.2%) IJCP and 207(14.6%) ISCP with a median follow-up of 3.5 years(Inter-quartile range: 1.5–7.5 years). Diabetes occurred at 11.5, 28 and 5.8 years(p < 0.001) while steatorrhea occurred at 16, 24 and 18 years(p = 0.004) after onset for ACP, IJCP and ISCP respectively. Local complications including pseudocysts occurred predominantly in ACP(p < 0.001). Ten-year risk of pancreatic cancer was 0.9%, 0.2% and 5.2% in ACP, IJCP and ISCP, respectively(p < 0.001). Pain resolution occurred more frequently in patients with older age of onset[Multivariate Hazard Ratio(HR):1.7(95%CI:1.4–2.0; p < 0.001)], non-smokers[HR:0.51(95%CI:0.34–0.78); p = 0.002] and in non-calcific CP[HR:0.81(0.66–1.0); p = 0.047]. Occurrence of steatorrhea[HR:1.3(1.03–1.7); p = 0.028] and diabetes[HR:2.7(2.2–3.4); p < 0.001] depended primarily on age at onset. Occurrence of pancreatic cancer depended on age at onset[HR:12.1(4.7–31.2); p < 0.001], smoking-history[HR:6.5(2.2–19.0); p < 0.001] and non-alcoholic etiology[HR:0.14(0.05–0.4); p < 0.001].ConclusionACP, IJCP and ISCP represent distinct entities with different natural course. Age at onset of CP plays a major prognostic role in all manifestations, with alcohol predominantly causing local inflammatory complications.     

Predictors and Prognostic Impact of Nutritional Changes After Transcatheter Aortic Valve Replacement

BackgroundLittle is known about changes in nutritional status as an index of frailty on clinical outcomes after transcatheter aortic valve replacement (TAVR). This study aimed to assess the clinical impact of serum albumin changes after TAVR.MethodsChanges in serum albumin levels from baseline to 1 year after TAVR were evaluated in 1524 patients who were classified as having hypoalbuminemia (<3.5 g/dl) and normoalbuminemia (≥3.5 g/dl) at each timepoint. The patients were categorized into 4 groups: NN (baseline normoalbuminemia, 1-year normoalbuminemia: n = 1119), HN (baseline hypoalbuminemia, 1-year normoalbuminemia: n = 202), NH (baseline normoalbuminemia, 1-year hypoalbuminemia: n = 121), and HH (baseline hypoalbuminemia, 1-year hypoalbuminemia: n = 82). We also defined late hypoalbuminemia as hypoalbuminemia identified at the 1-year assessment. Clinical outcomes were compared among 4 groups. Multivariable analysis was driven to assess the variables associated with late hypoalbuminemia and long-term mortality.ResultsThe cumulative 3-year mortality was significantly different among the 4 groups (NN: 11.4%, HN: 10.7%, NH: 25.4%, HH: 44.4%, p < 0.001). Multivariable Cox regression analysis revealed that the NH group had a higher mortality risk (hazard ratio [HR]; 2.80 and 3.53, 95% confidence interval [CI]; 1.71–4.57 and 2.06–6.06, p < 0.001 and p < 0.001, respectively), whereas the HN group had a similar risk (HR; 1.16, 95% CI; 0.66–2.06, p = 0.61) compared with the NN group. Baseline hypoalbuminemia, low body mass index, liver disease, peripheral artery disease, and hospital readmission within 1 year were predictors of late hypoalbuminemia (all p < 0.05).ConclusionSerial albumin assessment may identify poor prognostic subsets in patients with persistent and late acquired malnutrition after TAVR.     

Risk stratification and prognostic factors in patients with unresectable undifferentiated carcinoma of the pancreas

BackgroundUndifferentiated carcinoma (UC) of the pancreas has been considered a highly aggressive malignancy. However, only a few studies have systematically described the clinical course of UC patients. The aim of this study was to clarify the prognosis and construct a prognostic model for patients with unresectable UC.MethodsThis study was conducted at 17 institutions in Japan, and a total of 55 patients were analyzed.ResultsThe median overall survival (OS) of patients with unresectable UC was 3.95 months. In the multivariate Cox proportional hazards (CPH) model, age ≥65 years, Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, and C-reactive protein (CRP) >10 mg/L were independent prognostic factors for OS (age ≥65 years: hazard ratio [HR], 2.732; 95% confidence interval [CI], 1.353–5.515; ECOG PS ≥ 2: HR, 7.866; 95% CI, 1.981–31.241; CRP >10 mg/L: HR, 1.956; 95% CI, 1.013–3.775). Based on the β coefficients from the CPH model, the prognostic scores were defined as follows: age ≥65 years (3 points), ECOG PS ≥ 2 (6 points), and CRP >10 ml/L (2 points). The final prognostic model was the sum of the points. The derived prognostic model stratified patients into high-risk (score ≥4) and low-risk (score 0–3) groups, with significant differences in OS (1.45 vs. 8.19 months, respectively; p < 0.001).ConclusionsThe prognostic model stratified patients into high-risk and low-risk groups. These findings suggest that this model can serve as a tool for patient information and decision-making with regard to the therapeutic strategy for UC.     

Respect - A multicenter retrospective study on preoperative chemotherapy in locally advanced and borderline resectable pancreatic cancer

BackgroundNeoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.MethodsData on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.ResultsPatients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).ConclusionsRepresenting one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.     

Clinical implications of the serum CA19-9 level in “biological borderline resectability” and “biological downstaging” in the setting of preoperative chemoradiation therapy for pancreatic cancer

BackgroundBiological factors are emphasized in borderline resectable pancreatic cancer (BRPC), and CA19-9 is an important factor for biological borderline resectability (b-BR). The aim of this study was to investigate the cut-off value of CA19-9 for biological borderline resectability and “biological downstaging” in chemoradiation therapy (CRT) for pancreatic cancer (PC).MethodsA total of 407 patients with anatomically resectable PC (a-R) and BRPC (a-BR) received preoperative gemcitabine-based CRT. The b-BR was determined, according to the CA19-9 value prior to preoperative CRT (pre-CA19-9), as the subgroup of a-R cases in which the survival was comparable with that in a-BR cases. “Biological downstaging” was determined based on prognostic analyses regarding the CA19-9 value after preoperative CRT (post-CA19-9) in association with the survival of R cases (a-R cases without the b-BR factor).ResultsThe 5-year survival of a-R patients with pre-CA19-9 > 120 U/mL was comparable with that of a-BR patients (44% vs 34%, p = 0.082). The survival of b-BR patients with post-CRT CA19-9 ≤ 37 U/mL (normalized) was comparably favorable with that of R patients (56% vs 65%, p = 0.369). The incidence of distant recurrence was higher in b-BR patients without post-CA19-9 normalization than in those with post-CA19-9 normalization (70% vs 50%, p = 0.003), while the incidence of local recurrence was comparable between these two groups (12% vs 13%, p = 0.986).ConclusionsBiological BRPC was determined to be an anatomically resectable disease with pre-CA19-9 > 120 U/mL, and post-CA19-9 normalization indicated “biological downstaging” in b-BR in the preoperative CRT strategy.     

Eicosapentaenoic acid levels predict prognosis of peripheral artery disease caused by aortoiliac artery lesions

Background and aimEicosapentaenoic acid (EPA) has been reported to improve clinical outcome of high-risk atherosclerotic patients. We investigated whether endogenous EPA values predict prognosis of peripheral artery disease (PAD) patients.Methods and resultsThis retrospective study included 166 consecutive patients who had received endovascular therapy (EVT) for PAD caused by aortoiliac artery lesions. Patients were divided into 2 groups using median preoperative EPA value (57 μg/ml): LOW EPA (n = 83) and HIGH EPA (n = 83). We compared differences between the 2 groups in prevalence of major adverse limb events (MALE) which included target lesion revascularization (TLR), non-TLR, and major amputation, and major adverse events (MAE) which included MALE and all cause death. At a median follow-up period of 20 months, MALE had occurred in 24 LOW EPA patients (28.9%) and in 12 HIGH EPA patients (14.5%) (p = 0.04), and MAE had occurred in 41 LOW EPA patients (49.4%) and in 21 HIGH EPA patients (25.3%) (p < 0.01). Kaplan–Meier analysis showed prevalence of MALE and MAE was significantly higher in LOW EPA than in HIGH EPA (long-rank test χ² = 8.5, p < 0.01, log-rank test χ² = 13.2, p < 0.01, respectively). Multivariate Cox regression revealed preoperative EPA value < 57 μg/ml was an independent predictor for MALE (hazard ratio [HR]: 2.70; 95% CI: 1.35 to 5.4; p < 0.01) and MAE (HR: 2.86; 95% CI: 1.67 to 4.91; p < 0.01).ConclusionsEndogenous EPA value seems to be associated with risk of MALE and MAE after EVT in patients with PAD caused by aortoiliac artery lesions.     

Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy - A multicenter cohort study

Background/ObjectiveThe benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC.MethodsPatients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated.Results214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3–4 82 months median OS, p = 0.002), preoperative serum CEA (CEA <0.5 ng/ml 128 vs. CEA >0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 < 40 IU/ml 147 vs. CA19-9 > 40IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p < 0.001), N stage (N0 159 vs. N+ 110 months, p < 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997–3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904–3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151–0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients.ConclusionAdjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC.     

New scoring system for resectable hepatocellular carcinoma with a maximum tumor size of ≤5 cm based on preoperative tumor factors

BackgroundThe aim of this study was to establish a new scoring system for hepatocellular carcinoma (HCC) that can be used to predict the postoperative prognosis of HCC patients.MethodsA total of 359 HCC patients who underwent hepatectomy were included in this study. All eligible patients were randomly allocated to derivation cohort or validation cohort samples. We assigned one point each for preoperative factors identified in the derivation cohort, and the sum of the scores was used to classify the patients into high-risk and low-risk groups. The scoring system established using the derivation cohort was fitted to the validation cohort.ResultsThe prognosis of the high-risk group was significantly poorer than that of the low-risk group in both the derivation and validation samples (p = 0.04, p < 0.01, respectively). In the high-risk group, major hepatectomy resulted in a significantly better prognosis than minor hepatectomy in both samples (p = 0.04, p = 0.03, respectively). On the other hand, the extent of hepatectomy did not influence the prognosis of the low-risk group in either sample (p = 0.14, p = 0.34, respectively).ConclusionOur new scoring system can predict the treatment outcome of patients undergoing curative hepatectomy for HCC and could help determine the optimal extent of resection.     

Deep-Learning Models for the Echocardiographic Assessment of Diastolic Dysfunction

ObjectivesThe authors explored a deep neural network (DeepNN) model that integrates multidimensional echocardiographic data to identify distinct patient subgroups with heart failure with preserved ejection fraction (HFpEF).BackgroundThe clinical algorithms for phenotyping the severity of diastolic dysfunction in HFpEF remain imprecise.MethodsThe authors developed a DeepNN model to predict high- and low-risk phenogroups in a derivation cohort (n = 1,242). Model performance was first validated in 2 external cohorts to identify elevated left ventricular filling pressure (n = 84) and assess its prognostic value (n = 219) in patients with varying degrees of systolic and diastolic dysfunction. In 3 National Heart, Lung, and Blood Institute–funded HFpEF trials, the clinical significance of the model was further validated by assessing the relationships of the phenogroups with adverse clinical outcomes (TOPCAT [Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function] trial, n = 518), cardiac biomarkers, and exercise parameters (NEAT-HFpEF [Nitrate’s Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction] and RELAX-HF [Evaluating the Effectiveness of Sildenafil at Improving Health Outcomes and Exercise Ability in People With Diastolic Heart Failure] pooled cohort, n = 346).ResultsThe DeepNN model showed higher area under the receiver-operating characteristic curve than 2016 American Society of Echocardiography guideline grades for predicting elevated left ventricular filling pressure (0.88 vs. 0.67; p = 0.01). The high-risk (vs. low-risk) phenogroup showed higher rates of heart failure hospitalization and/or death, even after adjusting for global left ventricular and atrial longitudinal strain (hazard ratio [HR]: 3.96; 95% confidence interval [CI]: 1.24 to 12.67; p = 0.021). Similarly, in the TOPCAT cohort, the high-risk (vs. low-risk) phenogroup showed higher rates of heart failure hospitalization or cardiac death (HR: 1.92; 95% CI: 1.16 to 3.22; p = 0.01) and higher event-free survival with spironolactone therapy (HR: 0.65; 95% CI: 0.46 to 0.90; p = 0.01). In the pooled RELAX-HF/NEAT-HFpEF cohort, the high-risk (vs. low-risk) phenogroup had a higher burden of chronic myocardial injury (p < 0.001), neurohormonal activation (p < 0.001), and lower exercise capacity (p = 0.001).ConclusionsThis publicly available DeepNN classifier can characterize the severity of diastolic dysfunction and identify a specific subgroup of patients with HFpEF who have elevated left ventricular filling pressures, biomarkers of myocardial injury and stress, and adverse events and those who are more likely to respond to spironolactone.     

The long-term prognostic value of E/e’ in patients with ST segment elevation myocardial infarction

ObjectivesThis study aimed to evaluate the long-term prognostic value of E/e’ ratio in patients with ST-segment elevation myocardial infarction (STEMI).MethodsWe retrospectively assessed 314 patients who underwent primary coronary interventions between January 2010 and December 2015. The included patients were classified into two groups according to the E/e’ ratios: E/e’<15 (n = 245) and E/e’≥15 (n = 69). We investigated the incidence of major adverse cardiac events (MACEs) from the event to the final follow-up period of at least three years.ResultsA total of 55 cases of MACEs occurred during the follow-up. The E/e’≥15 group showed a significantly higher rate of MACEs than the E/e’<15 group (34.8% vs. 12.7%, p < 0.001). Among the MACE, the percentage of cardiac deaths (17.4% vs. 0.4%, p < 0.001) was higher in the E/e’≥15 group than in the E/e’<15 group. In the multivariable model, E/e’≥15 was demonstrated as the strongest prognostic factor for MACEs (hazard ratio [HR], 2.597; 95% confidence interval [CI], 1.294–5.211; p = 0.007) and cardiac death (HR, 27.537; 95% CI, 3.287–230.689; p = 0.002), while left ventricular ejection fraction (LVEF) was not. Neither the discrepancy of systolic nor diastolic function between initial and follow-up echocardiography affected the overall prevalence of MACEs. A disparity was observed between the two groups, with a significant increase in the rate of MACEs in the E/e’≥15 group (log-rank test, p < 0.001).ConclusionThe baseline E/e’≥15 in patients with STEMI after successful reperfusion is the strongest predictor of poor long-term clinical outcomes among those analyzed.     

Delayed return of gastrointestinal function after hepatectomy in an ERAS program: incidence and risk factors

BackgroundDelayed return of gastrointestinal function (DGIF) after hepatectomy can involve increased morbidity and prolonged hospital stay. Yet, data on incidence and risks factors are lacking.MethodsAll consecutive patients who underwent hepatectomy between June 2018 and December 2020 were included. All patients were included in an enhanced recovery after surgery (ERAS) program. DGIF was defined by the need for nasogastric tube (NGT) insertion after surgery. DGIF risk factors were identified.ResultsOverall, 206 patients underwent hepatectomy. DGIF occurred in 41 patients (19.9%) after a median time of 2 days (range, 1–14). Among them, 6 patients (14.6%) developed aspiration pneumonia, of which one required ICU for mechanical ventilation. DGIF developed along with an intraabdominal complication in 7 patients (biliary fistula, n = 5; anastomotic fistula, n = 1; adhesive small bowel obstruction, n = 1). DGIF was associated with significantly increased severe morbidity rate (p = 0.001), prolonged time to normal food intake (p < 0.001) and hospital stay (p < 0.001) and significantly decreased overall compliance rate (p = 0.001). Independent risk factors of DGIF were age (p < 0.001), vascular reconstruction (p = 0.007), anaesthetic induction using volatiles (p = 0.003) and epidural analgesia (p = 0.004). Using these 4 variables, a simple DGIF risk score has been developed allowing patient stratification in low-, intermediate- and high-risk groups.ConclusionDGIF after hepatectomy was frequently observed and significantly impacted postoperative outcomes. Identifying risk factors remains critical for preventing its occurrence.     

Long-Term Prognostic Value of Stress CMR in Patients With Heart Failure and Preserved Ejection Fraction

ObjectivesThe objectives of this study were to investigate the long-term prognostic value of inducible myocardial ischemia assessed by vasodilator stress cardiovascular magnetic resonance (CMR) in patients with HFpEF.BackgroundSome studies suggest that ischemia could play a key role in HF in patients with preserved ejection fraction (HFpEF).MethodsBetween 2008 and 2019, consecutive patients prospectively referred for stress CMR with HFpEF as defined by current guidelines, without known coronary artery disease (CAD), were followed for the occurrence of major adverse cardiovascular events (MACE), as defined by cardiovascular mortality or nonfatal myocardial infarction (MI). Secondary composite outcomes included cardiovascular mortality or hospitalization for acute HF. Cox regression analysis was performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR.ResultsAmong the 1,203 patients with HFpEF (73 ± 13 years of age; 29% males) who underwent stress CMR and completed follow-up (6.9 years interquartile range [IQR]: 6.7 to 7.7 years]), 108 experienced a MACE (9%). Kaplan-Meier analysis showed inducible ischemia and LGE were significantly associated with MACE (HR: 6.63; 95% confidence interval [CI]: 4.54 to 9.69; and HR: 2.56; 95% CI: 1.60 to 4.09, respectively; both p < 0.001) and secondary outcomes (HR: 8.40; 95% CI: 6.31 to 11.20; p < 0.001; and HR: 1.87; 95% CI: 1.27 to 2.76, respectively; p = 0.002). In multivariate analysis, inducible ischemia and LGE were independent predictors of MACE (HR: 6.10; 95% CI: 4.14 to 9.00; p < 0.001 and HR: 1.62; 95% CI: 1.06 to 2.49; p = 0.039; respectively).ConclusionsStress CMR-inducible myocardial ischemia and LGE have accurate discriminative long-term prognostic value in HFpEF patients without known CAD to predict the occurrence of MACE.     

Locally advanced pancreatic cancer: a reliable contraindication to resection in the modern era?

BackgroundThe aim of this study is to present radiologically designated LAPC found to be resectable upon surgical exploration and evaluate the outcomes of such resections.MethodsSequential LAPC patients between 2013 and 2019 were staged and underwent resection were included in the analysis of both perioperative and long-term outcomes.ResultsTwenty-eight patients with radiologically-designated LAPC underwent surgical resection after chemotherapy with a median follow-up of 31.7 m,75% underwent pancreaticoduodenectomy. The margin positivity and local recurrence rates were 21.4% and 35.7%, respectively. When compared to the 30 BRPC controls, the LAPC group had a higher rates of an arterial resection (11vs.1; p = 0.002), but the groups were similar with regard to all other preoperative and intraoperative variables (p < 0.05). Perioperative morbidity rates were similar (25.9%vs21.4%; p = 0.53). The LAPC and BRPC groups were also equivalent with respect to median recurrence-free survival (9.0mo; 95%CI 6.3, 11.7vs.8.3mo; 95%CI 5.4, 11.2) and median overall survival (19.9mo; 95%CI 17.0, 22.7 vs. 19.9mo; 95%CI 14.8, 25.1), respectively.ConclusionDespite a radiologic designation of locally advanced pancreatic cancer, certain subtypes of LAPC warrant surgical exploration provided the operative surgeon is prepared for major arterial and/or venous resection. Pancreatectomy in these patients has acceptable morbidity and oncologic outcomes, similar to patients who are radiologically borderline resectable.     

Regional lymph node sampling in hepatoma resection: insight into prognosis

BackgroundThe importance of regional lymph node sampling (LNS) during resection of hepatocellular carcinoma (HCC) is poorly understood. This study sought to ameliorate this knowledge gap through a nationwide population-based analysis.MethodsPatients who underwent liver resection (LR) for HCC were identified from Surveillance, Epidemiology and End Results (SEER-18) database (2003–2015). Cohort-based clinicopathologic comparisons were made based on completion of regional LNS. Propensity-score matching reduced bias. Overall and disease-specific survival (OS/DSS) were analyzed.ResultsAmong 5395 patients, 835 (15.4%) underwent regional LNS. Patients undergoing LNS had larger tumors (7.0vs4.8 cm) and higher T-stage (30.9 vs. 17.6% T3+, both p < 0.001). Node-positive rate was 12.0%. Median OS (50 months for both) and DSS (28 vs. 29 months) were similar between cohorts, but node-positive patients had decreased OS/DSS (20/16 months, p < 0.01). Matched patients undergoing LNS had equivalent OS (46 vs. 43 months, p = 0.869) and DSS (27 vs. 29 months, p = 0.306) to non-LNS patients. The prognostic impact of node positivity persisted after matching (OS/DSS 24/19 months, p < 0.01). Overall disease-specific mortality were both independently elevated (overall HR 1.71-unmatched, 1.56-matched, p < 0.01; disease-specific HR 1.40-unmatched, p < 0.01, 1.25-matched, p = 0.09).ConclusionRegional LNS is seldom performed during resection for HCC, but it provides useful prognostic information. As the era of adjuvant therapy for HCC begins, surgeons should increasingly consider performing regional LNS to facilitate optimal multidisciplinary management.     

Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction

BackgroundClonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown.ObjectivesThe purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology.MethodsThe study cohort comprised 62 patients with HF and LVEF <45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization.ResultsCHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology.ConclusionsSomatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.     

Ischemic Burden Reduction and Long-Term Clinical Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention

ObjectivesThe authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief.BackgroundThe clinical benefit of CTO PCI is questioned.MethodsIn a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [¹⁵O]H₂O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min^?1 · g^?1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction.ResultsAfter a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus <3 segment PD reduction (p < 0.01; risk-adjusted p = 0.04; hazard ratio [HR]: 0.34 [95% confidence interval (CI): 0.13 to 0.93]) and with hMBF increase above (Δ≥1.11 ml · min^?1 · g^?1) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min^?1 · g^?1 (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min^?1 · g^?1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04).ConclusionsPatients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.     

Changes in the prognostic values of modern cardiovascular biomarkers in relation to duration of diabetes mellitus

BackgroundBased on the complex pathophysiology of type 2 diabetes and atherosclerosis we hypothesized a dynamic change in prognostic value of cardiovascular biomarkers over time.MethodsIn this prospective study 746 patients with type 2 diabetes mellitus, being followed up for 60 months were analysed. The primary endpoint was defined as unplanned hospitalization for cardiovascular disease or death. Beside others, especially the prognostic performance of the biomarkers of interest (GDF-15, NT-proBNP, hs-TnT) was evaluated in relation to quartiles of diabetes duration.ResultsIn patients having a diabetes duration below 7 years lnGDF-15 (HR 2.84; p < 0.01) and lnhs-TnT (HR 2.96; p < 0.01) were significant predictors of the primary endpoint. LnAge (HR 40.01; p < 0.01) and lnNT-proBNP (HR 1.56; p = 0.03) were significant predictors in patients with a diabetes duration between 7 and 12 years. In the third quartile (diabetes duration 12–22 years) lnurinary albumin to creatinine ratio (HR 1.25; p = 0.005) and lnNT-proBNP (HR 2.13, p < 0.001) predicted the endpoint. In patients with a diabetes duration above 22 years, lnAge (HR 75.35; p = 0.001) and lnNT-proBNP (HR 2.0; p < 0.01) were the only significant predictors of the endpoint.ConclusionPrognostic power of cardiovascular biomarkers changes dynamically in relation to duration of type 2 diabetes mellitus. In patients with shorter duration of the disease markers of subclinical cardiovascular dysfunction and inflammation perform better than markers of systemic advanced organ dysfunction and cardiovascular disease.     

Hepatocellular carcinoma in patients with no identifiable risk factors

BackgroundA subset of patients have no risk factors for the development of hepatocellular carcinoma (HCC). We evaluated differences in clinical variables between patients with and without risk factors who underwent surgical resection.MethodsA prospectively maintained database was queried for patients who underwent R0/R1 resection of HCC between 1992 and 2016. Risk factors included HCV, HBV, hemochromatosis, alcoholic liver disease, or cirrhosis, stage 2 or 3 fibrosis or severe (>66%) steatosis of the non-neoplastic liver. Variables were compared between patients with and without risk factors.ResultsThere were 416 patients who underwent resection; 276 (66%) had known risk factors while 140 (34%) did not. Patients without risk factors were more likely to be older, female and have hyperlipidemia or coronary artery disease (p < 0.004). These patients had larger tumors and were more likely to undergo major hepatectomy (p < 0.001). There was no difference in OS (5-year, 56% vs 47%, p = 0.335), RFS (27% vs 24%, p = 0.398), or the rates of intrahepatic (HR:1.16 [95%CI:0.95–1.57], p = 0.344) and extrahepatic recurrences (HR:0.72 [95%CI:0.4–1.3], p = 0.261) between groups.ConclusionPatients without risk factors for HCC presented with larger tumors yet had similar outcomes, suggesting these tumors may represent a different disease process, and underlying liver dysfunction can influence overall outcome.     

Postoperative biliary anastomotic strictures after pancreaticoduodenectomy

BackgroundBiliary anastomotic stricture (BAS) is an uncommon complication of pancreaticoduodenectomy (PD). As PDs are performed more frequently, BAS may become a more common pathologic entity requiring clinical engagement. The aim of this study was to report the incidence of BAS in the modern era of pancreatic surgery and identify risk factors associated with it.MethodsPatients undergoing PD at the Johns Hopkins Hospital between 2007 and 2016 were identified using an institutional registry and clinicopathological features were analyzed to identify risk factors associated with BAS.ResultsOf 2125 patients identified, 103 (4.9%) developed BAS. Factors independently associated with BAS included laparoscopic approach (HR:2.83,95%CI:1.35–5.92, p = 0.006), postoperative pancreatic fistula (HR:2.45,95%CI:1.56–4.16,p < 0.001), postoperative bile leak (BL) (HR:5.26,95%CI:2.45–11.28,p < 0.001), and administration of adjuvant radiation therapy (HR:6.01,95%CI:3.19–11.34,p < 0.001). Malignant pathology was associated with lower rates of BAS (HR:0.52,95%CI:0.30–0.92, p = 0.025). BL was associated with higher rates of early-BAS (HR:16.49,95%CI:3.28–82.94, p = 0.001) while use of Vicryl suture for biliary enteric anastomosis was associated with lower rates of early-BAS (HR:0.20,95%CI:0.05–0.93, p = 0.041).ConclusionApproximately 5% of patients undergoing PD experience BAS. Multiple factors are associated with the development and timing of BAS.