Variation in incidence, prevention and treatment of persistent air leak after lung cancer surgery.

OBJECTIVES: Persistent air leak (PAL; >5 days after surgery) is the most common complication after pulmonary resection and associated with prolonged hospital stay and increased morbidity. Literature is contradictory about the prevention and treatment of PAL. Variation is therefore hypothesized. The aim of this study is to understand the variation in the incidence, preventive management and treatment of PAL. METHODS: Data from the Dutch Lung Cancer Audit for Surgery were combined with results of an online survey among Dutch thoracic surgeons. The national incidence of PAL and case-mix corrected between-hospital variation were calculated in patients who underwent an oncological (bi)lobectomy or segmentectomy between January 2012 and December 2018. By multivariable logistic regression, factors associated with PAL were assessed. A survey was designed to assess variation in (preventive) management and analysed using descriptive statistics. Hospital-level associations between management strategies and PAL were assessed by univariable linear regression. RESULTS: Of 12 382 included patients, 9.0% had PAL, with a between-hospital range of 2.6-19.3%. Factors associated with PAL were male sex, poor lung function, low body mass index, high American Society of Anesthesiologists (ASA) score, pulmonary comorbidity, upper lobe resection, (bi)lobectomy (vs segmentectomy), right-sided tumour and robotic-assisted thoracic surgery. Perioperative (preventive) management of PAL differed widely between hospitals. When using water seal compared to suction drainage, the average incidence of PAL decreased 2.9%. CONCLUSIONS: In the Netherlands, incidence and perioperative (preventive) management of PAL vary widely. Using water seal instead of suction drainage and increasing awareness are potential measures to reduce this variation.

Incidence and Clearance of Penile High-Risk Human Papillomavirus Infection and Their Determinants Among HIV-Negative Men Who Have Sex With Men.

BACKGROUND: Men who have sex with men (MSM) are at increased risk of anogenital human papillomavirus (HPV) infections. We aimed to assess the incidence and clearance of penile high-risk HPV (hrHPV) infections and their determinants among HIV-negative MSM living in the Netherlands. METHODS: Between 2010 and 2015, HIV-negative MSM were semiannually tested for penile HPV and completed detailed questionnaires on health and sexual behavior. Self-collected penile swabs were tested for HPV DNA using SPF10-PCR DEIA/LiPA25 system. Type-specific hrHPV incidence (IR) and clearance rates (CR) were calculated for 12 hrHPV types (HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, HPV-39, HPV-45, HPV-51, HPV-52, HPV-56, HPV-58, and HPV-59). Determinants of incidence and clearance of HPV-16 and HPV-18, separately, and combined 7 hrHPV types covered by the nonavalent vaccine were assessed by Poisson regression using generalized estimating equations for combined hrHPV types. RESULTS: We included 638 HIV-negative MSM, with a median age of 38 (interquartile range, 33-43) years. HPV-16 had an IR of 4.9/1000 person-months of observation at risk (PMO; 95% confidence interval [95% CI], 3.8-6.3) and CR of 90.6/1000 PMO (95% CI, 60.7-135.1). The IR and CR of HPV-18 were 3.4/1000 PMO (95% CI, 2.5-4.5) and 119.2/1000 PMO (95% CI, 76.9-184.8), respectively. Age and condom use during insertive anal sex were not associated with hrHPV incidence, whereas high number of recent sex partners was. CONCLUSIONS: The relatively high IR and low CR of penile HPV-16 and HPV-18 among HIV-negative MSM correlates with their high prevalence and oncogenic potential. Incident HPV infections were associated with recent sexual risk behavior.

A Propensity Score-Matched Cohort Study to Evaluate the Association of Lymph Node Retrieval with Long-Term Overall Survival in Patients with Esophageal Cancer.

BACKGROUND: Previous studies evaluating the association of lymph node (LN) yield and survival presented conflicting results and many may be influenced by confounding and stage migration. OBJECTIVE: This study aimed to evaluate whether the quality indicator 'retrieval of at least 15 LNs' is associated with better long-term survival and more accurate pathological staging in patients with esophageal cancer treated with neoadjuvant chemoradiotherapy and resection. METHODS: Data of esophageal cancer patients who underwent neoadjuvant chemoradiotherapy and surgery between 2011 and 2016 were retrieved from the Dutch Upper Gastrointestinal Cancer Audit. Patients with < 15 and ≥ 15 LNs were compared after propensity score matching based on patient and tumor characteristics. The primary endpoint was 3-year survival. To evaluate the effect of LN yield on the accuracy of pathological staging, pathological N stage was evaluated and 3-year survival was analyzed in a subgroup of patients with node-negative disease. RESULTS: In 2260 of 3281 patients (67%) ≥ 15 LNs were retrieved. In total, 992 patients with ≥ 15 LNs were matched to 992 patients with < 15 LNs. The 3-year survival did not differ between the two groups (57% vs. 54%; p = 0.28). pN+ was scored in 41% of patients with ≥ 15 LNs versus 35% of patients with < 15 LNs. For node-negative patients, the 3-year survival was significantly better for patients with ≥ 15 LNs (69% vs. 61%, p = 0.01). CONCLUSIONS: n this propensity score-matched cohort, 3-year survival was comparable for patients with ≥ 15 LNs, although increasing nodal yield was associated with more accurate staging. In node-negative patients, 3-year survival was higher for patients with ≥ 15 LNs.

Population-based study on practice variation regarding preoperative systemic chemotherapy in patients with colorectal liver metastases and impact on short-term outcomes.

INTRODUCTION: Definitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands. MATERIALS AND METHODS: All patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality. RESULTS: In total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98-1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81-1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75-2.09, p = 0.467) was found. CONCLUSION: Significant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found.

Letter to the editor: female sex workers and HPV vaccine.

When considering what the scientific evidence is for the potential added value to offer HPV vaccines to sex workers, not only its potential role for female sex workers should be examined, but its role for all those who conduct sex work. Our initial paper looked at the evidence in terms of HPV vaccine immunogenicity, efficacy, effect on transmission, induction of mucosal immunity, and not at implementation. Brown and Cabral considered our omission to address the aspects of implementation an 'academic mistake'. We disagree; implementation aspects are complex and require analyses of multiple barriers, and how to address these. It only makes sense to discuss these if there is scientific evidence for its implementation; otherwise offering the vaccine is not useful.

Variation in length of stay after minimally invasive lung resection: a reflection of perioperative care routines?

OBJECTIVES: Good perioperative care is aimed at rapid recovery, without complications or readmissions. Length of stay (LOS) is influenced not only by perioperative care routines but also by patient factors, tumour factors, treatment characteristics and complications. The present study examines variation in LOS between hospitals after minimally invasive lung resections for both complicated and uncomplicated patients to assess whether LOS is a hospital characteristic influenced by local perioperative routines or other factors. METHODS: Dutch Lung Cancer Audit (surgery) data were used. Median LOS was calculated on hospital level, stratified by the severity of complications. Lowest quartile (short) LOS per hospital, corrected for case-mix factors by multivariable logistic regression, was presented in funnel plots. We correlated short LOS in complicated versus uncomplicated patients to assess whether short LOS clustered in the same hospitals regardless of complications. RESULTS: Data from 6055 patients in 42 hospitals were included. Median LOS in uncomplicated patients varied from 3 to 8 days between hospitals and increased most markedly for patients with major complications. Considerable between-hospital variation persisted after case-mix correction, but more in uncomplicated than complicated patients. Short LOS in uncomplicated and complicated patients were significantly correlated (r = 0.53, P < 0.001). CONCLUSIONS: LOS after minimally invasive anatomical lung resections varied between hospitals particularly in uncomplicated patients. The significant correlation between short LOS in uncomplicated and complicated patients suggests that LOS is a hospital characteristic potentially influenced by local processes. Standardizing and optimizing perioperative care could help limit practice variation with improved LOS and complication rates.

Should female sex workers be offered HPV vaccination?

Prophylactic vaccines are efficacious in preventing Human Papillomavirus (HPV) infection and subsequent cervical intraepithelial neoplasia (CIN), cervical cancer, other anogenital cancers, and anogenital warts. Female sex workers (SW) are at increased risk of acquiring sexually transmitted infections, including HPV. There are several reasons to offer HPV vaccination to SW: they are at high risk for HPV and often unvaccinated, and the immunogenicity of the vaccine is also excellent in previously HPV exposed women. Furthermore, women with disease caused by HPV may still benefit from vaccination. The efficacy of vaccinating mid-adult women (26-44 years old) against persistent HPV infection and CIN2+ is good. Although an SW may have been infected or exposed to HPV, she may not have been exposed to all vaccine-included hrHPV types. Vaccination induces mucosal immunity via the production of neutralizing antibodies on the surface of the female genital tract, thus preventing potential transmission to clients. Nevertheless, some considerations argue against offering vaccination to SWs. Current vaccines are only prophylactic and as such, do not affect current HPV infections. Women who have previously cleared HPV infections, may do so again and thus not need vaccination. Fewer SW might be naïve to HPV-types than currently thought. HPV vaccination has probably no effect on latent infections. Vaccinating sometime after sexual debut could be too late, as infections have already occurred. Taken together, some data suggest that vaccination of SW may offer health benefits, also for the community, but sufficient evidence is lacking. In certain cases, HPV vaccination of SW may be recommended. Evidence-based, public health decisions concerning vaccination of SW are challenging and could be facilitated with more research in this high-risk group.

Incidence and Clearance of Anal High-risk Human Papillomavirus Infections and Their Determinants Over 5 Years Among Human Immunodeficiency Virus-negative Men Who Have Sex With Men.

BACKGROUND: We aimed to assess the incidence and clearance of anal high-risk human papillomavirus (hrHPV) infections and determinants thereof among human immunodeficiency virus (HIV)-negative men who have sex with men (MSM) over a period of up to 5 years. METHODS: From 2010 to 2015, HIV-negative MSM were followed every 6 months. Anal self-swabs were collected at inclusion and every 6 months thereafter, and were HPV genotyped using the SPF10-PCR DEIA/LiPA25-system-v1. Incidence rates (IRs) and clearance rates (CRs) of incident anal hrHPV infections were assessed by hrHPV type (types 16, 18, 31, 33, 45, 52, and 58). Determinants of transitions between uninfected and infected states were assessed by hrHPV type using a time-homogenous multi-state Markov model. RESULTS: This study included 713 HIV-negative MSM, with a median age of 37 years (interquartile range [IQR] 31-43) and a median number of study visits of 6 (IQR 2-7). The IRs of anal infections had a median of 5.2 per 100 person-years (range: 2.2-7.9) across types, with HPV16 having the highest IR. The CRs of incident anal hrHPV infections had a median of 53.7 per 100 person-years (range: 33.4-65.3) across types, with HPV16 having the lowest CR. Having had over 100 lifetime sex partners was significantly associated with incident anal hrHPV infections in multivariable analyses. CONCLUSIONS: The high incidence and low clearance rates of anal HPV16 infection, compared to other hrHPV types, is consistent with HPV16 being implicated in the large majority of anal cancer cases.

Type-Specific Anal Human Papillomavirus Prevalence Among Men, According to Sexual Preference and HIV Status: A Systematic Literature Review and Meta-Analysis.

Background: Anal human papillomavirus (HPV) infection, most notably HPV16, the central cause of anal cancer, is increased by anal sexual intercourse and worsened by human immunodeficiency virus (HIV)-positivity. Methods: A systematic review and meta-analysis of type-specific anal HPV prevalence in men, compared according to sexual preference, HIV status, and, when available, anal cytopathology. Results: Seventy-nine eligible studies included: 1805 HIV-negative men who have sex with women (MSW), 924 HIV-positive MSW, 8213 HIV-negative men who have sex with men (MSM), and 12758 HIV-positive MSM. Irrespective of anal cytopathology, HPV16 prevalence was significantly higher in MSM than MSW, both among HIV-negative (14% vs 3%; prevalence ratio (PR) 4.7; 95% confidence interval [CI] 2.5-8.9) and HIV-positive men (30% vs 11%; PR = 2.8; 95% CI, 1.9-4.1). Likewise, HPV16 was significantly higher in HIV-positive than HIV-negative men, both among MSW (PR = 3.5; 95% CI, 1.6-7.7) and MSM (PR = 2.1; 95% CI, 1.8-2.5). Anal HPV16 prevalence was similar between HIV-positive MSW and HIV-negative MSM. For MSM, anal HPV16 prevalence was significantly higher from studies with anal cytopathology, suggesting population sampling effects. Conclusion: Sexual preference and HIV infection are independent strong determinants of male anal HPV16 infection, confirming HIV-positive MSM as priorities for anal cancer prevention.

Virological and Serological Predictors of Anal High-grade Squamous Intraepithelial Lesions Among Human Immunodeficiency Virus-positive Men Who Have Sex With Men.

BACKGROUND: Our objective was to identify virological and serological predictors of anal high-grade squamous intraepithelial lesions (HSIL) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). METHODS: HIV-positive MSM were recruited from a longitudinal study during which anal self-swabs and serum were collected at up to 5 bi-annual visits. Swabs were human papillomavirus (HPV) genotyped, and the type-specific HPV viral load in the anal swabs was determined. Serum antibodies to the E6, E7, E1, E2, and L1 proteins of 7 high-risk HPV (hrHPV) types and HPV6 and 11 were analyzed. The participants who had a high-resolution anoscopy after the last study visit were included in the current analysis. Anal HSIL was diagnosed by histopathological examinations of anal biopsies. The causative HPV type of anal HSIL was determined in whole tissue sections (WTS) and by laser capture micro-dissection if more than one HPV-type was found in WTS. Multivariable logistic regression was used to study whether persistent anal HPV infections, HPV viral loads, and seropositivity for HPV were predictors of anal HSIL, either in general or caused by the concordant HPV type. RESULTS: Of 193 HIV-positive MSM, 50 (26%) were diagnosed with anal HSIL. HrHPV persistence in anal swabs was common, varying by hrHPV type between 3-21%. Anal HPV persistence was the only determinant independently associated with anal HSIL, both in general and by concordant, causative HPV type. CONCLUSIONS: Persistent HPV infections were strongly associated with anal HSIL, in general as well as for the concordant HPV type.

Detection Rate of High-Grade Squamous Intraepithelial Lesions as a Quality Assurance Metric for High-Resolution Anoscopy in HIV-Positive Men.

BACKGROUND: High-resolution anoscopy-guided biopsies are the gold standard for identifying anal intraepithelial neoplasia, but diagnosing high-grade squamous intraepithelial lesions depends on the skills of the anoscopist. OBJECTIVE: This study aims to validate the high-grade squamous intraepithelial lesion detection rate as a quality assurance metric for high-resolution anoscopy in HIV-positive men. DESIGN: This is a retrospective study. SETTING: This study was conducted at 3 HIV outpatient clinics in Amsterdam, The Netherlands. PATIENTS: HIV-positive men who have sex with men were selected for this study. MAIN OUTCOME MEASURES: We analyzed the high-grade squamous intraepithelial lesion detection rate per high-resolution anoscopy, the mean number of biopsies taken, and the mean high-grade squamous intraepithelial lesion rate per biopsy in time-subsequent groups for 7 anoscopists performing high-resolution anoscopy. RESULTS: Seven anoscopists performed high-resolution anoscopy in 1340 HIV-positive men who have sex with men. The overall high-grade squamous intraepithelial lesion detection rate for all 7 anoscopists combined increased significantly over time, from 27% to 40% (p < 0.001; OR, 1.15; 95% CI, 1.08-1.23 per 50 high-resolution anoscopies). The mean number of biopsies increased significantly from 1.4 (22% high-grade squamous intraepithelial lesions per biopsy) to 2.0 biopsies per patient (29% high-grade squamous intraepithelial lesions per biopsy) (p < 0.001). Three anoscopists showed a significant increase in proportion of high-grade squamous intraepithelial lesions per biopsy with increasing experience. LIMITATIONS: There were statistically significant differences, with limited clinical significance, in the characteristics of patient populations between anoscopists and clinics. CONCLUSIONS: We found significant variations in the high-grade squamous intraepithelial lesion detection rate among anoscopists performing high-resolution anoscopy in HIV-positive men who have sex with men. The high-grade squamous intraepithelial lesion detection rate and mean high-grade squamous intraepithelial lesion rate per biopsy can be used as a quality assurance metric to follow up the learning curve of high-resolution anoscopists. See Video Abstract at http://links.lww.com/DCR/A555.

Anal HPV 16 and 18 viral load: A comparison between HIV-negative and -positive MSM and association with persistence.

Does anal HPV viral load explain the difference in anal HPV persistence between HIV-negative and -positive men who have sex with men (MSM)? MSM ≥18 years were recruited in Amsterdam, the Netherlands, in 2010-2011. Anal self-swabs were collected every 6 months and genotyped (SPF10 -PCR-DEIA-LIPA25 -system). HPV16 and HPV18 load was determined with a type specific quantitative (q)PCR, and compared between HIV-negative and -positive men using ranksum test. Persistence was defined as ≥3 positive samples for the same HPV-type. Determinants of persistent HPV16/18 infection and its association with HPV16/18 load were assessed with logistic regression. Of 777 recruited MSM, 54 and 22 HIV negative men were HPV16 and HPV18 positive at baseline, and 64 and 39 HIV-positive MSM. The geometric mean titer (GMT) of HPV16 was 19.6 (95%CI 10.1-38.0) and of HPV18 8.6 (95%CI 2.7-27.5) DNA copies/human cell. HPV16 and HPV18 load did not differ significantly between HIV-negative and -positive MSM (P = 0.7; P = 0.8, respectively). In multivariable analyses HPV16 load was an independent determinant of HPV16 persistence (OR 1.8, 95%CI 1.3-2.4). No difference in anal HPV viral load was found between HIV-positive and HIV-negative MSM. HPV 16/18 viral load is an independent determinant of type-specific persistence.

Risk factors for anal high-grade squamous intraepithelial lesions in HIV-positive MSM: is targeted screening possible?

OBJECTIVE: HIV-positive MSM are at increased risk for developing anal squamous cell carcinoma. Detection of precursor lesions of anal cancer [anal high-grade squamous intraepithelial lesions (HSIL)] is cumbersome and expensive. Our objective was to identify potential risk factors for anal HSIL in HIV-positive MSM to develop more stringent screening criteria. DESIGN: We studied a cohort of MSM screened by high-resolution anoscopy at three HIV clinics in Amsterdam, the Netherlands. METHODS: For every first high-resolution anoscopy performed in a patient, we analyzed five demographic and seven HIV-related potential risk factors for four different outcome measures: histologically proven anal HSIL vs. no squamous intraepithelial lesions (SIL), HSIL-anal intraepithelial neoplasia 2 vs. no SIL, HSIL-anal intraepithelial neoplasia 3 vs. no SIL, and HSIL vs. no HSIL. We used univariable and multilevel, multivariable logistic regression. RESULTS: From 2008 through 2015, 497 out of 1678 (30%) screened HIV-positive MSM had anal HSIL. The mean age was 49 years (SD 9.6), 96% used combination antiretroviral therapy, and median duration of combination antiretroviral therapy use was 7.8 years (interquartile range 4.0-12.4). Increasing age [adjusted odds ratio (aOR) 0.82, 95% confidence interval (CI) 0.70-0.94, P = 0.006] and years living with suppressed viral load [1-5 years suppressed aOR 0.52 (95% CI 0.34-0.80), 5.01-10 years aOR 0.47 (95% CI 0.29-0.74), >10 years aOR 0.54 [0.34-0.87], all compared to less than 1 year suppressed, P = 0.009] were found to be protective for HSIL vs. no SIL. CONCLUSION: Young HIV-positive MSM without viral suppression are statistically at highest risk for anal HSIL, but given the high prevalence among all virally suppressed men, we advise that all HIV-positive MSM should be screened for HSIL.

Determinants of Human Papillomavirus Vaccination Intention Among Female Sex Workers in Amsterdam, the Netherlands.

INTRODUCTION: Female sex workers (FSWs) are at risk for human papillomavirus (HPV)-induced diseases but are currently not targeted by the HPV vaccination program in the Netherlands. We explored determinants of their intention to get vaccinated against HPV in case vaccination would be offered to them. METHODS: In 2016, FSWs 18 years and older having a sexually transmitted infection consultation with the Prostitution & Health Center (P&G292) in Amsterdam, either at the clinic or at their working location, were invited to complete a questionnaire assessing sociopsychological determinants of HPV vaccination intention (scale ranging from -3 to +3). Determinants of HPV vaccination intention were assessed with univariable and multivariable linear regression. In addition, we explored the effect of out-of-pocket payment on intention. RESULTS: Between May and September 2016, 294 FSWs participated. The median age was 29 years (interquartile range, 25-37 years). Human papillomavirus vaccination intention was high (mean, 2.0; 95% confidence interval [CI], 1.8-2.2). In multivariable analysis, attitude (ß = 0.6; 95% CI, 0.5-0.7), descriptive norm (ß = 0.2; 95% CI, 0.1-0.3), self-efficacy (ß = 0.2; 95% CI, 0.1-0.3), beliefs (ß = 0.1; 95% CI, 0.0-0.2), and subjective norm (ß = 0.1; 95% CI, 0.0-0.2) seemed to be the strongest predictors of HPV vaccination intention (R = 0.54). Human papillomavirus vaccination intention decreased significantly to a mean of 0.2 when vaccination would require out-of-pocket payment of &OV0556;350. CONCLUSIONS: The HPV vaccination intention among FSWs seems relatively high and is most strongly constituted in attitudinal, normative, and self-efficacy beliefs. Out-of-pocket payment will probably have a negative impact on their HPV vaccination acceptability.