Acute rupture or erosion of a coronary atheromatous plaque and subsequent coronary artery thrombosis cause the majority of sudden cardiac deaths and myocardial infarctions. Cigarette smoking is a major risk factor for acute coronary thrombosis. Indeed, a majority of sudden cardiac deaths attributable to acute thrombosis are in cigarette smokers. Both active and passive cigarette smoke exposure seem to increase the risk of coronary thrombosis and myocardial infarctions. Cigarette smoke exposure seems to alter the hemostatic process via multiple mechanisms, which include alteration of the function of endothelial cells, platelets, fibrinogen, and coagulation factors. This creates an imbalance of antithrombotic/prothrombotic factors and profibrinolytic/antifibrinolytic factors that support the initiation and propagation of thrombosis.

Mechanisms of Coronary Thrombosis in Cigarette Smoke Exposure

Beyond the already well-established strong causative relationship with cancer, smoking increases the risk for vascular disease. Smoking may act directly or adversely influence risk factors contributing to the development of vascular disease. Smoking causes endothelial dysfunction, dyslipidemia (decreased high-density lipoprotein cholesterol levels, hypertriglyceridemia and increased oxidation of low-density lipoprotein cholesterol) and platelet activation leading to a prothrombotic state. Smoking increases emerging risk factors (eg, fibrinogen, homocysteine, and high-sensitivity C-reactive protein) and increases insulin resistance and the risk of developing type 2 diabetes mellitus. The beneficial effects of statins and antioxidants (eg, vitamins C and E, beta-carotene) are counteracted by smoking. Smoking-induced alterations in growth factors, adhesion molecules, and even in genes can accelerate the progression of atherosclerosis. The aim of this review is to consider the adverse consequences of smoking on the factors predisposing to vascular disease and to emphasize the beneficial effects of smoking cessation.

Influence of Smoking on Predictors of Vascular Disease

Excess weight is the most prevalent cardiovascular risk factor and certainly the factor that improves the least over time among those with established cardiovascular disease. The association between obesity and cardiovascular disease is complex and not limited to the standard risk factors like hypertension, dyslipidemia, and type 2 diabetes mellitus. In recent years, multiple studies have shown that obesity may cause cardiovascular diseases via multiple disease mechanisms like subclinical inflammation, endothelial dysfunction, increased sympathetic tone, atherogenic lipid profiles, enhanced thrombogenic factors and also through obstructive sleep apnea. Despite the overwhelming data linking obesity to cardiovascular disease, several studies have shown a paradoxical association between obesity and prognosis among those with coronary disease and heart failure, which may be due to limitations of the way we currently define obesity. There is abundant data suggesting that measuring central obesity or total body fat content might be more appropriate than using the body mass index alone. The management of obesity is challenging and studies using lifestyle modification alone or with pharmacologic agents generally have limited success and high levels of weight regain. Bariatric surgery has proven to be an effective and safe way to induce and maintain significant weight loss but is limited to those with medically complicated obesity or people who are severely obese.

Obesidad y corazón

Platelet activation and aggregation play pivotal roles in the thrombotic process of acute coronary syndromes. However, data regarding platelet count and its association with clinical outcomes in the setting of ST-elevation myocardial infarction (STEMI) are limited. We hypothesized that higher platelet counts on presentation would be associated with poorer clinical outcomes. Data from 10,793 patients with STEMI in the Thrombolysis In Myocardial Infarction (TIMI) trials database were analyzed. Mean platelet count on presentation was 254.8 x 10(3)/microl. Higher platelet counts were associated with higher rates of adverse clinical outcomes at 30 days. In a multivariable analysis that adjusted for confounders of platelet counts (age, gender, weight, diabetes, and smoking), higher platelet counts remained associated with an increased risk of the combined end point of death, reinfarction, and congestive heart failure. With a reference group of platelet counts 400 x 10(3)/microl. Further, a greater decrease in follow-up platelet counts (compared with baseline values) was independently associated with an increased risk of reinfarction at 30 days (odds ratio 1.44 for every decrease of 100 x 10(3)/microl unit of platelets, 95% confidence interval 1.13 to 1.82, p = 0.03). In conclusion, in STEMI, a higher platelet count on presentation was independently associated with adverse clinical outcomes, whereas a greater subsequent platelet count decrease was associated with an increased risk of reinfarction.

Association of platelet counts on presentation and clinical outcomes in ST-elevation myocardial infarction (from the TIMI Trials).

Background and Purpose—The so-called smoking-thrombolysis paradox of an improved outcome after thrombolysis was first described in smokers with myocardial infarction. We investigated whether reperfusion rates and clinical outcome differ between smokers and nonsmokers with ischemic stroke after intravenous tissue plasminogen activator. Methods—Consecutive acute ischemic stroke patients, who had magnetic resonance imaging before and 1 day after thrombolysis, were included for analysis. All of the patients received intravenous tissue plasminogen activator within 4.5 hours. Reperfusion was defined as a 75% reduction in perfusion deficit (mean transit time >6 s) after thrombolysis compared with baseline. Magnetic resonance angiography was used to evaluate arterial stenosis and occlusion. Functional outcome was assessed 3 months after stroke using the modified Rankin Score. Results—Of 148 patients, 21.6% were smokers (n=32). Smokers were younger (median, 61 years [SD, 9.4 years] versus 75 years [SD, 11.6 years]...

Smoking-Thrombolysis Paradox Recanalization and Reperfusion Rates After Intravenous Tissue Plasminogen Activator in Smokers With Ischemic Stroke

Background: Despite increased risk for coronary artery disease and acute myocardial infarction (AMI), smokers have a paradoxically lower mortality after thrombolysis for AMI than non-smokers. We determined the clinical risk profiles and coronary flow characteristics of patients in the TIMI trials according to smoking status, focusing on microvascular flow. 
Methods: Among 2,573 patients in the TIMI 4, 10A, 10B and TIMI 14 trials, epicardial flow post-thrombolysis was measured using angiographic TIMI flow grades and the corrected TIMI frame count (CTFC). Microvascular flow was measured by TIMI Myocardial Perfusion Grade (TMPG) and, in TIMI 14, the percentage of ST segment resolution. 
Results: Clinically, the mean age (54 vs. 62 years), the prevalence of diabetes mellitus (11% vs. 16%) and hypertension (26% vs. 40%), and the 30-day mortality (2.6% vs. 6.2%) were lower among smokers than non-smokers (all p ≤ 0.001). Angiographically, single-vessel disease (48% vs. 40%) and non-left anterior descending infarct arteries (65.4% vs. 60.8%) were more common among smokers (both p ≤ 0.01). Epicardial TIMI grade 3 flow was achieved more often in smokers than non-smokers (61% vs. 56%) and the CTFC was faster (34 vs. 37 frames/sec, both p ≤ 0.01), especially in LAD lesions. However, the frequency of normal microvascular flow (TMPG 3) was similar among smokers and non-smokers (24% vs. 29%, p = 0.16), as was the frequency of complete ST segment resolution (50% vs. 46%, p = 0.29). 
Conclusions: Smokers have lower mortality after AMI than non-smokers, due in large part to lower clinical risk profiles and faster epicardial flow. Differences in tissue-level perfusion do not appear to contribute to lower mortality in smokers. 
Abbreviated Abstract. After acute MI, active smokers have lower acute mortality than non-smokers that appears to be largely explained by their healthier risk profiles, less extensive coronary disease, and faster epicardial blood flow after thrombolysis. Microvascular injury does not appear to play a major role in the lower mortality risk among smokers.

The smoker's paradox: insights from the angiographic substudies of the TIMI trials.

Journal HPB Surgery HP001 PREOPERATIVE DIABETES MELLITUS AND KEY PANCREATODUODENECTOMY OUTCOMES: IS THE TIMING OF THE DIABETES DIAGNOSIS RELEVANT? DANIEL CROAGH AND RAW STUDY COLLABORATORS Monash Health, Victoria Background: Pancreatoduodenectomy (PD) remains a high-risk operation. Although patients with diabetes mellitus (DM) are known to have impaired immune function, the impact of DM on PD outcomes remains debated. This study aimed to investigate the impact of DM on selected shortand longterm PD outcomes. Methods: Data was extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective cohort study of outcomes of PD performed for pancreatic head malignancy (29 centres in 8 countries, n = 1484). Patients with a preoperative diagnosis of DM were compared to those who did not. The following outcomes were measured: median length of stay (LoS), pancreatic fistula (PF), 30-day readmission, 90-day mortality, and five-year survival (FYS). Analyses were performed using the Mann– Whitney U test and Fisher’s exact test. Results: Of the 1484 included patients, 277 had a prior diagnosis of DM. When those with DM were compared to those who did not, PF (13.0% vs. 14.4%, P = 0.6), 30-day readmission (10.8% vs. 8.6%, P = 0.2), 90-day mortality (5.4% vs. 3.3%, p = 0.1) and FYS (28.5% vs. 32.5%, P = 0.2) rates were all similar. However, LoS was significantly longer in the former (14 vs. 13 days, p = 0.04). Of those with DM, 29.6% had received their diagnosis in the year leading up to their resection. These patients had significantly higher rates of five-year recurrence compared to those with established DM (74.1% vs. 57.3%, P = 0.03) but FYS rates were similar (29.3% vs. 30.6%, P = 1.0). Conclusion: In this study, PD patients with a preoperative diagnosis of DM had similar outcomes to those without DM. Patients diagnosed with DM in the year leading up to their resection had higher rates of disease recurrence than diabetics who received their diagnosis more than 1 year prior to PD. HP002 LAPAROSCOPIC DISTAL PANCREATECTOMY WITH PARTIAL SPLENECTOMY PRESERVES SPLENIC FUNCTION ADAM MCNAMARA, DANIEL KILBURN AND NICHOLAS O’ROURKE University of Queensland, Queensland Background: Splenectomy is known to carry a significant risk of severe sepsis. Current guidelines suggest involved vaccination schedules and long term antibiotic therapy. We postulate that preservation of 20%–30% of splenic volume via partial splenectomy when performing distal pancreatectomy preserves splenic function and subsequent immunocompetence. Methods: Three patients have undergone distal pancreatectomy with partial splenectomy. The distal pancreatectomy is performed as usual. The lower pole of the spleen is removed en bloc with the distal pancreas. The spleen is divided using a Ligasure and linear stapler along the line of demarcation of short gastric supply. Temporary clamping of the short gastric arteries reduces blood loss. All operations were completed laparoscopically. All were completed within 3 h, with the partial splenectomy component adding approximately 30 min. Lesions resected include an enlarging serous cystadenoma, a pseudocyst and a pancreatic adenocarcinoma. All lesions involved splenic vessels, making Kimura or Warshaw procedures untenable. No patient required blood transfusion. One patient suffered a post-operative collection requiring 10 days of drainage. Follow up imaging demonstrated persisting viable spleen, of reasonable size. Twelve month post-operative blood films demonstrated normal red cell morphology without asplenic features such as Howell-Jolly bodies. Conclusion: Distal pancreatectomy with partial splenectomy offers the benefits of splenic preservation in patients who have tumours involving splenic vessels. Although adding half an hour to the procedure, partial splenectomy is possible, and can provide long term benefits for these patients. HP003 EARLY RECURRENCE AFTER RESECTION OF COLORECTAL LIVER METASTASES: FROM CLINICAL DATA TO PROTEOMIC BIOMARKER DISCOVERY GEOFFREY YUET MUN WONG, MATTHEW MCKAY, NAZIM BHIMANI, CONNIE DIAKOS, MARK P HUGH AND THOMAS J HUGH The University of Sydney, New South Wales Purpose: To discover prognostic proteomic biomarkers for early intrahepatic recurrence after resection of colorectal liver metastases (CRLM). Methodology: We performed a retrospective review of the Upper Gastrointestinal Surgical Unit Liver Resection Database from 2005 to 2017 to assess the timing and site of recurrence for patients with CRLM. Early recurrence was defined as recurrence within 6 months of surgery and patients with durable remission as 10-year recurrence-free survival. We obtained freshfrozen CRLM tissue and conducted label-free, data-dependent acquisition, liquid-chromatography mass spectrometry using an HF-X Orbitrap mass spectrometer. Mass spectrometric data were analysed using MaxQuant (2.0.1.0). Peptides were identified by their fragmentation spectra using Andromeda and a 1% false discovery rate. Quantitative proteomic analysis was performed using Perseus (1.6.2.3). Proteins that were upregulated or downregulated by at least 2-fold and P < 0.05 were considered significant. Results: Early recurrence occurred in 58 of 194 patients (29.9%). Tissue samples from 24 patients with early intrahepatic recurrence and 22 patients with durable remission were selected for proteomic analysis. In total, 6224 proteins were identified. Calponin-2, fibulin-5, versican core protein, amyloid-beta precursor protein, and glutathione peroxidase 3 were upregulated in early recurrence. Sulfotransferase 1A1, arylsulfatase E, fatty acid-binding protein 1, ATP synthase subunit delta, macrophage metalloelastase, and brain-specific angiogenesis inhibitor 1-associated protein 2 were downregulated in early recurrence. Conclusion:We discovered 11 lead proteomic biomarkers for early intrahepatic recurrence after resection of CRLM from two well-defined cohorts. HP004 IMPLICATIONS OF UNPLANNED CONVERSIONS IN MINIMALLY-INVASIVE PANCREATODUODENECTOMY: A SYSTEMATIC REVIEW AND META-ANALYSIS MATTHEW MARSHALL-WEBB, SHAHID ULLAH, SAVIO GEORGE BARRETO AND MONISH KARUNAKARAN Flinders Medical Centre, South Australia Background and Aims: Minimally-invasive pancreatoduodenectomy (MIPD) is associated with more complication-related deaths (LEOPARD-2), pronounced volume-outcome relationship and a long learning curve. Rates of conversion to open for MIPD have been reported to be as high as 40%. Unplanned conversions in minimally-invasive colorectal and liver surgery have resulted in worse outcomes. However, their implications in MIPD have not been elucidated. This study aimed to compare peri-operative outcomes of (unplanned) converted MIPD against both successfully completed MIPD and upfront open PD. Methods: Systematic review of major reference databases (PubMed/ Medline, Google Scholar and Cochrane Library) was undertaken, and metaanalysis performed using fixedor random-effects model. Results: Six studies involving 20 267 patients who met the inclusion criteria were analysed. Risk factors for conversion include male gender, older age, tumours >4 cm, of pancreaticobiliary origin, and vascular, or multi-visceral, involvement. Meta-analysis demonstrated unplanned conversions were associated with increased 30-day mortality compared to open PD (RR = 2.3 CI 0.95–5.72; P = 0.0662; I = 79%) and successfully completed MIPD (RR = 2.83 CI 1.62–4.93; P < 0.0002; I = 0%), and overall morbidity compared to successfully completed MIPD (RR = 1.41 CI 1.09–1.82, P < 0.0087, I = 82%). Conclusion: Unplanned conversions during MIPD are associated with increased overall morbidity compared to successfully completed MIPD, and ANZ J. Surg. 2023; 93 (S1) 88–98 Editorial material and organization © 2023 Royal Australasian College of Surgeons Copyright of individual abstracts remains with the authors. increased 30-day mortality compared to successfully completed and upfront open PD. The risk factors highlighted must be considered when selecting patients for surgery, and designing training/proctorship programs. HP005 USE OF SELECTIVE INTERNAL RADIOTHERAPY (SIRT) FOR AUGMENTATION OF FUTURE LIVER REMNANT (FLR): INITIAL EXPERIENCE IN AN AUSTRALIAN HEPATOBILIARY UNIT ALISTAIR ROWCROFT, MATTHEW TRINDER, MANDI MAUNDURA, LAURENCE WEBBER, MAYANK BHANDARI AND MO BALLAL Fiona Stanley Hospital, Western Australia Outline: Liver-directed therapy with SIRT has been well-established as primary treatment for hepatocellular carcinoma (HCC), as well as palliative treatment for non-HCC tumours. Evidence is emerging for the use of SIRT radiation lobectomy to induce hypertrophy in the future liver remnant (FLR) prior to resection. This study aims to quantify our experience with SIRT as a bridge to surgical resection. Methods: A retrospective analysis was performed on all patients undergoing SIRT from January 2017 to January 2022. All patients were reviewed at a combined Hepatobiliary and Hepatology multidisciplinary team meeting prior to SIRT treatment with yttrium-90. Results: A total of 132 SIRT procedures were performed in 111 patients over the 5 year study period. The median age of patients was 65 years, and overall SIRT was well tolerated with a low complication rate and one 30 day mortality (0.9%). 15 patients underwent SIRT as a bridge to surgical resection, with 8 patients achieving their target surgery after a mean of 7.2 months following SIRT. Eight patients were evaluated with perioperative liver scintigraphy and CT volumetry, with mean Mebrofenin extraction pre-SIRT 2.6%/min/m and remnant volume 30.8% increasing to 3.6%/min/ m and 42% respectively post-SIRT. There were no instances of posthepatectomy liver failure in those patients undergoing surgery. Conclusions: In this cohort SIRT was overall safe and resulted in increased FLR function and volume in those patients undergoing liver resection. Future evidence should aim to compare SIRT with other techniques of FLR augmentation. HP0

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/ans.18404

Matthew McKay

Papers

The smoker's paradox: insights from the angiographic substudies of the TIMI trials.

Abstract Journal HPB Surgery