Obstructive Sleep Apnea and Pathological Characteristics of Resected Pancreatic Ductal Adenocarcinoma

Abstract

BackgroundProspective studies have identified obstructive sleep apnea (OSA) as a risk factor for increased overall cancer incidence and mortality. The potential role of OSA in the risk or progression of specific cancers is not well known. We hypothesized that pathological differences in pancreatic cancers from OSA cases compared to non-OSA cases would implicate OSA in pancreatic cancer progression.MethodsWe reviewed the medical records of 1031 patients who underwent surgical resection without neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2003 and 2014 and compared the TNM classification of their cancer and their overall survival by patient OSA status.ResultsOSA cases were significantly more likely than non-OSA cases to have lymph node-negative tumors (37.7% vs. 21.8%, p = 0.004). Differences in the prevalence of nodal involvement of OSA vs. non-OSA cases were not associated with differences in other pathological characteristics such as tumor size, tumor location, resection margin status, vascular or perineural invasion, or other comorbidities more common to OSA cases (BMI, smoking, diabetes). A logistic regression model found that a diagnosis of OSA was an independent predictor of lymph node status (hazard ratio, 0.051, p = 0.038). Patients with OSA had similar overall survival compared to those without OSA (HR, 0.89, (0.65–1.24), p = 0.41).ConclusionThe observed pathological differences between OSA-associated and non-OSA-associated pancreatic cancers supports the hypothesis that OSA can influence the pathologic features of pancreatic ductal adenocarcinoma.

The Association of Sleep Apnea and Cancer in Veterans

“…Indeed, previous work has shown potential associations between OSA and increased incidence of several specific cancers. 24,[31][32][33][34][35][36] Given that differential associations with specific cancer sites are likely to be obscured in analyses of all cancers combined, it will be important to assess if these associations exist, and to what extent they exist, in this cohort of veteran patients. Additionally, future analyses will include several potential proxies for CPAP usage and compliance, such as the frequency of CPAP supply refills.…”

“…[16][17][18][19][20][21][22][23] Several epidemiologic studies have further explored this association with mixed results. [24][25][26][27][28][29][30][31][32][33][34][35][36] A recent large-scale study of 5.6 million patients identified through a national health insurance database showed no increased cancer incidence overall, but did show positive associations between OSA and increased incidence of specific cancer types (kidney, pancreatic, and melanoma). 24 Two small studies showed a positive association between OSA severity and increased overall cancer incidence while another similar study showed no association.…”

“…[25][26][27] A handful of studies have also shown positive associations between OSA and increased incidence and aggressiveness of specific cancer types. [31][32][33][34][35][36] While several studies have evaluated the association between OSA and cancer, the results from these studies are not concordant and their study methodologies have differed. Furthermore, many of these studies have either been limited by small sample sizes, relatively short patient follow-up, and/or limited confounder adjustment.…”

“…An emerging body of evidence has suggested that OSA is also associated with cancer. 14-36 Studies have suggested that OSA may mechanistically promote the development of cancer through intermittent hypoxia and sleep fragmentation, leading to chronic oxidative stress and activation of factors that may support tumor angiogenesis, cell survival, metastasis, and aggressive cancer behavior. 14-21 Epidemiologic studies have tested this association with mixed results.…”

Obstructive sleep apnea and comorbidities: a dangerous liaison

“…Cancer mortality during follow up was increased in OSA patients compared to controls in general population samples [155, 156], cohorts of OSA patients [157], and cohorts of cancer patients [158], in association with OSA severity and duration of nocturnal hypoxemia. Some studies however did not show increased mortality associated with occurrence of OSA in the general population [159] or cohorts of cancer patients [160, 161].…”