In this retrospective analysis, encompassing a substantial cohort of 38,365 HCC patients, a notable 12.2% presented with constipation as a secondary diagnosis. The multifaceted approach to the study, employing multivariate regression analysis to account for confounding variables, provided a nuanced understanding of the diverse outcomes associated with constipation in this population.
Surprisingly, the study revealed a seemingly paradoxical association between constipation and reduced mortality, along with decreased total hospitalization charges. The nuanced exploration of secondary outcomes elucidates the complex interplay between constipation and various health events, including a decreased likelihood of obesity and acute respiratory failure but an increased risk of weight loss, nausea/vomiting, fatigue, palliative care involvement, malnutrition, and opioid use disorder.
Honda, et al. [8] conducted a study of 12,217 participants who were undergoing hemodialysis and experienced concurrent constipation. The participants were enrolled in the Japan-Dialysis Outcomes and Practice Patterns study. The primary endpoint of the study focused on mortality, while cause-specific death was considered as the secondary endpoint. The findings concluded that patients undergoing hemodialysis with concurrent constipation exhibited higher mortality rates compared to those without constipation [8].
In a retrospective analysis of a cohort of 3,359,653 US Veterans, Sumida, et al. [9] investigated the relationship between constipation and mortality. Their findings revealed that patients with constipation had a significantly higher all-cause mortality rate (hazard ratio [HR], 1.12; 95% CI, 1.11-1.13), indicating a potential connection between gastrointestinal health and overall longevity within this population.
However, in a study by Yoshida, et al. [10], it was found that mortality did not show an association with increased odds of mortality. The authors carried out a retrospective cohort study involving 1933 ICU patients from 2011-2018. The univariate analysis revealed that constipation was linked to decreased mortality in this patient population; however, the multivariate regression analysis indicated no association between constipation and increased mortality [10].
It is widely acknowledged that obesity is linked to a higher incidence of acute respiratory failures, which in turn can lead to increased mortality. Interestingly, lower rates of obesity and acute respiratory failures may have a protective effect on mortality. These findings warrant further exploration through prospective studies. Additionally, our analysis has revealed the need for more in-depth research into the impact of obesity on mortality in HCC patients. Several studies have reported associations between obesity and both acute respiratory failure as well as increased mortality. Our conclusions align with Flegal KM, et al. [11] systematic review and meta-analysis which highlighted the association between obesity and higher all-cause mortalit.
Several studies have shown the significant impact of chronic constipation on healthcare resource utilization. In 2010, Cai Q, et al. [12] conducted a retrospective analysis using the HealthCore Integrated Research Database to identify patients with chronic constipation, concluding that it poses a substantial burden on healthcare costs. Similarly, Fine PG, et al. [13] retrospective analysis from 2006-2014, utilizing the same database and focusing on cancer patients aged >18, revealed that opioid-induced constipation was associated with heightened healthcare resource utilization and economic burden among this cohort. Notably, our own study yielded different findings; however, there are several complex factors specific to our patient cohort that require careful consideration.
This calls for further investigation into the admission of patients with HCC cancers who are undergoing complex chemotherapeutic regimens that result in side effects such as constipation. Our study also indicates that these hospitalized patients experience increased nausea and vomiting, which could potentially be attributed to the side effects of chemotherapy medications. The adverse events leading to hospitalization may have necessitated the suspension of anticancer medications, possibly contributing to decreased hospitalization costs. However, NIS does not provide data on the treatment of medical conditions, highlighting the need for prospective studies to address this information gap and gain a better understanding of the reasons behind reduced hospitalization costs.
Our study revealed a significant correlation between constipation and opioid medication use among HCC patients. Additionally, the cohort with constipation exhibited a higher likelihood of experiencing malnutrition, fatigue, palliative care involvement, and a decreased incidence of obesity. While obesity is often associated with constipation, further exploration is necessary to elucidate how constipation impacts the odds of obesity. These studies may be more complex, as there are myriad factors that contribute to constipation to begin with such as diets low in fiber, inadequate fluid intake, different physical activity levels, opioid-use, pregnancy, stress and mental health. Other factors include comorbidities such as irritable bowel syndrome, hypothyroidism, diabetes, neurological disorders, or colon or rectal issues [14]. A review of literature yielded varying findings on the association between constipation and both malnutrition as well as overweight/obesity.
A cross-sectional analysis conducted by Yurtdaş Depboylu, et al. [15] encompassing 883 adults aged over 65 from nursing homes and community centers in Turkey concluded that there is an association between malnutrition and an increased risk of developing constipation. Larkin and colleagues conducted a comprehensive study to thoroughly investigate the relationship between palliative care and constipation. Their methodology involved meticulous scrutiny of existing literature and the development of evidence-based recommendations. The thorough analysis led to the significant finding that patients in palliative care settings face a heightened risk of experiencing constipation [16].
Dzierżanowski T, et al. [17] conducted an in-depth epidemiology study that involved 51 hospice and 49 nursing home patients. The predominant diagnosis among both sets of patients was cancer. Their research revealed a strong association between palliative care and constipation, highlighting the vulnerability of cancer patients under palliative care in both nursing homes and hospices to developing constipation. The results underline the need for a holistic understanding of constipation’s impact, considering both positive and negative aspects. While the reduced mortality and hospitalization costs are promising, the elevated risks of adverse health events emphasize the need for vigilance in managing constipation in HCC patients. The study also hints at the potential role of opioid use in shaping these outcomes, calling attention to the elaborate balance required in pain management strategies.
This study not only presents significant strengths but also notable weaknesses that merit thorough consideration. Being an administrative database, the NIS is susceptible to sampling bias due to potential inaccuracies in data entry, incomplete information, and coding discrepancies. While it offers extensive patient data, the absence of specific clinical details, laboratory findings, and post-discharge patient outcomes, could potentially influence the conclusions drawn from this study. The failure to consider outpatient care and readmissions following surgery makes it challenging to comprehensively assess long-term complications and fatalities using NIS data alone. Furthermore, the inpatient data does not provide insights into major events during surgery or complications that may impact length of stay and hospital costs with a level of depth necessary for comprehensive analysis. However, the study based on NIS has several advantages. One of its key strengths is the ability to evaluate a nationally representative study population derived from the largest publicly available inpatient database. This allows for the generation of comprehensive regional and national statistics and estimates on patient outcomes, inpatient utilization, healthcare costs, and various other related factors.
