Quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a narrative review

Introduction

The treatment of peritoneal metastases from intra-abdominal cancers has improved significantly over the past three decades due to the advent of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Without treatment, peritoneal carcinomatosis is a universally fatal diagnosis with a median survival of approximately 6 months (1). This dismal prognosis is improved by treatment with systemic chemotherapy, but with limited effectiveness possibly due in part to limited uptake across the peritoneum (2). HIPEC has gained popularity as a regional therapy allowing for direct application of chemotherapy to peritoneal disease intra-operatively; combined with the removal of all macroscopic tumor deposits, termed a complete cytoreduction, HIPEC can significantly improve long-term outcomes. Increases in survival after CRS/HIPEC have been observed in patients with peritoneal carcinomatosis from a wide variety of primary neoplasms including appendiceal neoplasms causing pseudomyxoma peritonei (PMP), colorectal cancer, ovarian cancer, mesothelioma, and gastric cancer (3-7).

Despite these survival benefits in well-selected patient populations, initial experiences with CRS/HIPEC were marred by high rates of peri-operative morbidity and mortality. Complete cytoreduction may involve a complete peritonectomy as well as the removal of involved segments of bowel or other intra-abdominal organs; this extensive resection can lead to prolonged operative times and elevated intra-operative risk (8). Early peri-operative mortality rates were observed to be as high as 5%, while the rates of significant morbidity in initial reports ranged from 25–45% (9-11). Toxicity from the HIPEC portion of the operation was similarly frequent with rates as high as 55–65% (12,13). Since these early studies were reported, there have been substantial improvements with increased experience at specialized centers, however, there has been a persistent misperception that CRS/HIPEC is an unusually morbid procedure. As shown by Foster et al. in a recent study of NSQIP data, CRS/HIPEC is a safe procedure with comparable morbidity rates to similarly high-risk intra-abdominal procedures such as an esophagectomy or Whipple procedure (14). Multiple other studies have similarly demonstrated the safety of CRS/HIPEC with acceptable morbidity and mortality rates, even at moderate volume centers (15-18).

Despite this improvement in overall morbidity and mortality, there remains significant concern that these major operations will adversely impact patients’ quality of life (QOL) post-operatively. A key factor in improving the patient experience with CRS/HIPEC has been careful patient selection. A patient’s disease burden is thoroughly assessed with diagnostic laparoscopy to determine the likelihood of a complete cytoreduction at the time of CRS/HIPEC (19). This prognostication is critically important as the completeness of cytoreduction is a leading factor in post-operative patient outcomes (20,21). As with other high-risk operations, overall patient health and performance status are also predictive of post-operative outcomes and should be weighed thoughtfully before offering surgery (22). Patients are evaluated by a multi-disciplinary team, and it is estimated that less than half of those referred for CRS/HIPEC ultimately undergo cytoreduction (23,24). By following this rigorous selection process, optimizing outcomes can be achieved across all age groups (25).

With CRS/HIPEC now recognized as a safe and effective procedure in well-selected populations, there has been an increasing focus on patients’ post-operative QOL. Short-term impairment of QOL is to be expected following CRS/HIPEC, as with any other major operation; however, the wide distribution of life expectancy across histologies illustrates the importance of optimizing QOL at varying time points. This recovery of QOL is multifactorial and depends on improvement in a patient’s symptoms as well as physical, functional, emotional, and social well-being. Evaluation of these factors begins in the pre-operative clinic, where it has been noted that depression, low emotional well-being, poor nutrition, and decreased overall QOL are all associated with worsened post-operative outcomes (26-28). Following surgery, each dimension of QOL requires specific attention from the multidisciplinary team. To design post-operative protocols and programs that address QOL, it is essential to understand how CRS/HIPEC affects each domain of QOL. In this narrative review, we explore the growing body of literature on post-operative QOL in CRS/HIPEC patients and identify where gaps in our knowledge remain. We present the following article in accordance with the narrative review checklist (available at http://dx.doi.org/10.21037/dmr-20-153).

Methods

Inclusion criteria

Published studies included in this review were required to meet a set of criteria pertaining to both patient populations and study design. Reviewed studies were required to include adult patients (≥18 years of age) undergoing CRS/HIPEC for peritoneal carcinomatosis from any intra-abdominal primary pathology. Only original randomized controlled, prospective cohort, or cross-sectional studies were eligible for inclusion. Lastly, only studies employing validated instruments for the measurement of healthcare-related QOL were included. Studies published in the English language at any time prior to our literature review in October 2020 were eligible for inclusion.

Study identification

The studies included in this review were initially identified by querying PubMed (MEDLINE) using search terms including “Cytoreductive Surgery”, “Heated Intraperitoneal Chemotherapy”, “Peritoneal Carcinomatosis”, “Post-Operative”, “Quality of Life”, “Well-Being”, and “Functional Status”. Potentially relevant studies from this search were included if they met the above-described criteria. The references from these studies and previous review articles in this initial search were reviewed as well; ultimately, 27 original articles were identified that met our criteria for review.

Narrative review

Results and conclusions from each of the 27 articles included in this review were examined and summarized. Study design, year of publication, number of patients, primary pathologies, QOL instruments used, and the timing of post-operative assessments were collected in order to characterize each study. Whether or not a baseline, pre-operative assessment was performed was recorded as well. For cross-sectional studies, the median or mean time to follow-up was reported based on available published data. The main conclusions from each article were recorded and summarized as well.

Discussion

Assessment of QOL

Multiple factors can impact patients’ QOL following CRS/HIPEC. Patients are often hampered by symptoms from either their disease or the operation, the most frequent of which are pain, diarrhea, constipation, dyspnea, and insomnia (29,30). Anorexia is a common symptom as well, and some patients may even require parenteral nutrition temporarily (31). Beyond somatic symptoms, patients may experience mood dysregulation with many suffering from persistent depression (32). Patients’ return to their home life can be complicated by decreases in their social well-being as well, and many experience temporary impairments in their functional well-being or performance status. Taken together, all of these factors lead to limitations in patients’ QOL immediately following CRS/HIPEC.

Efforts to mitigate this decrease in QOL depend on accurate measurement and evaluation in each separate domain of well-being. To this end, there are several validated instruments to measure QOL in cancer patients. The most commonly used general QOL questionnaires include the Short Form 36 (SF-36), the Functional Assessment of Cancer Therapy scale (FACT), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ) (33-37). The SF-36 is a 36-item questionnaire that assesses eight health domains and can be divided into broader physical and mental components; it is an effective tool for measuring general health perception as well as limitations due to physical, social, emotional, or functional issues (33). The FACT scale similarly measures physical, functional, social, and emotional well-being; the FACT-General (FACT-G) scale contains 28 items to assess QOL broadly, while the FACT-Colorectal (FACT-C) contains an additional colorectal cancer subscale with disease-specific items (34,35). The EORTC-QLQ similarly measures physical, role, emotional, cognitive, and social functioning over a 30-item general scale (EORTC-QLQ C30); as with the FACT-C scale, an additional eight-item colorectal cancer-specific subscale may be added (EORTC-QLQ CR38) (36,37). Overall functional and performance status is also assessed with the Eastern Cooperative Oncology Group (ECOG) scale in many CRS/HIPEC patients (38).

Many studies on QOL following CRS/HIPEC also employ more focused or disease-specific questionnaires. Pain is often evaluated using the Brief Pain Inventory (BPI), designed to assess both the intensity of pain and the interference pain creates in the patient’s life (39). Assessment of depression is validated using the Center for Epidemiological Studies Depression scale (CES-D), and sleep quality was assessed in one study on CRS/HIPEC patients using the Pittsburgh Sleep Quality Index (40,41). Less frequently used questionnaires include the Gastro-Intestinal Quality of Life Index, the Psychosocial Concerns questionnaire, and the Life Appreciation scale (42,43). While the SF-36, FACT-G, and EORTC-QLQ C30 were the most commonly encountered instruments in this review, each of these questionnaires has been used in the evaluation of post-operative CRS/HIPEC patients.

QOL studies in CRS/HIPEC patients (2001–2020)

There have been two previous systematic reviews of QOL after CRS/HIPEC that we were able to identify, both published in 2014 (44,45). Shan et al., in a review and meta-analysis of 15 studies, concluded that healthcare-related QOL declined post-operatively at the 3- to 4-month timepoint, but then improved to pre-operative levels at 12 months. Benefits beyond 12 months were less clear, but likely continued for multiple years in surviving patients (44). Seretis et al., reviewing 20 studies, likewise found that QOL decreases significantly in the acute post-operative period with improvement to approximately baseline levels between 6 and 12 months. Furthermore, this group concluded that QOL actually improved from baseline in long-term survivors beyond 12 months (45). Multiple additional studies have been published since the publication of these reviews, including several with larger sample sizes than any study from prior to 2014, prompting this updated review.

In our review of the literature published prior to October 2020, we were able to identify 27 studies on QOL after CRS/HIPEC (Table 1). Seventeen of these manuscripts were generated from prospective cohort studies, with one other paper using a retrospective review of prospectively collected QOL data; these papers using prospectively collected data had the advantage of measuring baseline QOL prior to surgery (29,30,32,42,46-59). One of these studies, and an additional eight papers, employed cross-sectional surveys of post-operative patients that tended to capture longer-term survivors from CRS/HIPEC (30,38,41,43,60-64). Lastly, one paper utilized QOL data collected during a clinical trial (65).

Given the low overall volume of CRS/HIPEC patients even at specialized centers, most studies included patients with multiple different primary histologies. For those that focused on a single histology, PMP was the most common diagnosis (30,50,53,63). The majority of studies had less than 100 patients enrolled, though samples sizes ranged from 5 to 598 patients. Follow-up intervals were variable, with 3 months being the most common timing of the initial post-operative QOL assessment. Eight studies included data from earlier than 3 months post-operatively, with the shortest interval being 2 weeks post-operatively in two separate studies (42,46,53,55,57-59,65). Follow-up in prospective studies typically continued for 12–24 months at regular intervals, with two studies continuing follow-up to 36 or 48 months (30,55). Attrition due to survival and patient response rates substantially impacted sample sizes at later timepoints in all studies, potentially limiting the utility of data from longer-term surveys in prospective cohorts. Cross-sectional studies, conversely, had mean or median follow-up intervals ranging from 10 months to 5 years.

Global QOL

Each study included in this review used metrics that allow us to examine post-operative QOL either globally or broken down into multiple domains. In aggregate, there was broad agreement that there is an acute worsening of QOL immediately following CRS/HIPEC. There were discrepancies, however, in the duration of this decline in QOL before returning to baseline. The most optimistic timing for a return to baseline came from the earliest study, by McQuellon et al. in 2001, suggesting that QOL improves by 3 months post-operatively (46). Importantly, the patients in this study were evaluated at 2 weeks post-operatively, allowing for relative improvements to be observed at the 3-month timepoint. Ford et al., in a cross-sectional study, similarly concluded that acceptable QOL can be achieved by 3 months, though pre-operative baseline QOL was not measured in this study (38).

The majority of studies, however, found that patients required between 6–12 months to recover to baseline QOL (Table 2). This group included the three largest studies by Dodson et al., Passot et al., and Stearns et al., accounting for 851 patients between them with a broad range of pathologies (30,42,56). Each of these three studies employed different instruments to measure QOL as well, potentially strengthening the broader consensus that QOL returns to baseline at 6–12 months.

Cross-sectional studies suggest that this improved overall QOL at 6–12 months is sustained in long-term survivors. These studies are limited by the lack of a baseline measurement of QOL prior to CRS/HIPEC, but they each independently conclude that patients achieve acceptable long-term QOL after surgery. Kirby et al. found similar results even in patients undergoing re-do CRS/HIPEC for PMP (63). Comparisons to control populations were not uniformly made, though Tan et al. and Chia et al. separately found that long-term QOL is similar to reference populations of cancer patients not undergoing CRS/HIPEC (62,64). Despite this adequate recovery, specific functional deficits remained in several studies, necessitating closer inspection of recovery in each domain of QOL.

Physical QOL

Trends in physical well-being mirrored those in global QOL in most studies. While a handful of studies stated that physical QOL improved to baseline levels by 3 to 4 months, the vast majority of prospective studies found that patients required at least 6–12 months to return to baseline levels. Thirteen separate studies independently identified somewhere between 6–12 months as the timepoint for recovery of baseline physical QOL (29,32,42,48-54,56-58). Three of these studies further stated that physical well-being on FACT-G can improve to above baseline levels at 12 months or later; however, results in survivors past 1 year are mixed (32,51,57). A recent paper by Stearns et al. suggested that 18 months is needed to return to baseline physical status (30). The 90 patients included in a study by Tsilimparis et al. experienced an even more prolonged recovery, with decreased physical functioning scores on EORTC QLQ-C30 persisting for 24 months post-operatively; a return to baseline was only observed in the six patients who survived and responded to follow-up at 36 months (55).

Long-term survivors assessed in cross-sectional studies also had mixed results for physical QOL, though they generally did not compare favorably with reference populations. Schmidt et al. and Duckworth et al. both found that physical QOL was below that of a general control population at a mean of 4 and 4.2 years, respectively (41,60). Tan et al. found no difference from a reference population of cancer patients, with Chia et al. finding similar results when comparing CRS/HIPEC patients to patients undergoing outpatient cancer treatment (62,64). The latter study compared CRS/HIPEC patients to metastatic or recurrent cancer patients as well, and in this instance CRS/HIPEC patients did have significantly higher physical functioning scores on EORTC QLQ-C30.

When viewed independently of a reference population, however, long-term survivors from CRS/HIPEC demonstrated adequate physical well-being. Zenasni et al. found that 95.7% of patients had high scores for physical functioning on EORTC QLQ-CR38 at a median of 2.4 years (61). McQuellon et al., in a 2003 study, similarly found high physical well-being scores in 17 patients at a mean of 5.3 years after surgery. Of these 17 patients, 10 had baseline QOL surveys completed at 6 months post-operatively, and over time they had shown significant improvement in physical QOL (43). While this is a small sample size, it is representative of a larger trend in the literature that physical QOL decreases in the first year after surgery before improvement to patients’ approximate baseline.

Emotional QOL and mental health

Relative to overall QOL, emotional QOL and mental health consistently took less time to recover to baseline levels or better. While overall QOL declines acutely post-operatively, there is no consensus across prospective studies that emotional health declines at all. Three separate studies found that emotional QOL did not change post-operatively, with Jess et al. showing a non-significant trend towards higher emotional functioning (29,50,52). Seven other studies did identify a significant increase in emotional QOL post-operatively; Stearns et al., Dodson et al., Hill et al., and McQuellon et al. in a 2008 paper all independently observed this improvement in emotional health beginning at the first post-operative assessment, occurring at 3 months post-operatively in each study (30,42,51,53,54,56,57). This timing of the first post-operative survey may mask a transient decrease in emotional health prior to 3 months, as Kopanakis et al. showed that emotional well-being decreased at 1 month prior to improving to above baseline levels at 3 months (57). Any decrease from baseline does not appear to be sustained, however, and the longest recovery time for emotional QOL in any study was 6 months.

This rapid recovery of baseline emotional QOL may be related to a relatively low baseline as many patients experience depressive symptoms both before and after surgery. Multiple studies included in this review from Wake Forest have used the CES-D to evaluate levels of clinically significant depression in post-operative CRS/HIPEC patients. The most recent paper from this group, by Ali et al., found that 31% of patients had scores on CES-D consistent with depression at baseline; this rate decreased initially post-operatively before increasing again to 37% of patients at 24 months (32). Even if rates of depression decrease in survivors post-operatively, they are persistently measured at 24–33% at 12 months (46,49,51,56).

Whether these seemingly high rates of depression are significantly different than the general population is not clear. Schmidt et al., Duckworth et al., and Tan et al. all showed that emotional well-being in CRS/HIPEC patients is similar to a control general population; these studies utilized combinations of the EORTC QLQ-C30, FACT-C, and SF-36 scales without CES-D, however, limiting our ability for comparison (41,60,62). Chia et al. showed that CRS/HIPEC long-term survivors do have higher emotional functioning scores on EORTC QLQ-C30 than both outpatient cancer patients and those with metastatic disease, arguing against long-term emotional health issues relative to similar patients (64). In aggregate, the evidence suggests that CRS/HIPEC patients experience a fairly quick recovery of emotional QOL while still experiencing persistent depression.

Social QOL

Various QOL instruments measure social well-being or QOL within the context of how patients’ illness and treatment affect their relationships with friends and family. Changes in social QOL tended to be subtle, with several papers identifying no significant change from baseline at any point post-operatively (48-52). Of these, two papers from McQuellon et al. did show a non-significant trend towards decreased social functioning on SF-36 at 12 months post-operatively (49,51).

Notably, each of these papers finding no change in social well-being were among the earliest studies on QOL after CRS/HIPEC. More recent, and often larger, studies consistently showed decreases in social QOL. For papers that did find a significant decrease in social QOL, recovery times were generally 12 months or longer, with larger cohorts from Stearns et al. and Tsilimparis et al. only achieving baseline levels at 18 or 24 months, respectively (30,42,53-55). Only one study found that patients never regained baseline social QOL, albeit the largest in this review; Dodson et al. showed that social well-being on FACT-C decreased at 3 months post-operatively and did not fully recover by 24 months (56). Ali et al. conversely found that social well-being increased post-operatively beginning at 3 months, though this finding was an outlier among all studies reviewed (32).

Results from cross-sectional studies were largely consistent with those from prospective studies. Zenasni et al. found that 88.4% of patients had high social functioning scores on EORTC QLQ-C30 at a median follow-up of 2.4 years, but other published data was more neutral with regard to social QOL in long-term survivors (61). Duckworth et al. found no difference between CRS/HIPEC patients and a general control population using multiple instruments, while Schmidt et al. found decreased scores on EORTC QLQ-C30 at a mean of 4 years when compared to a general population (41,60). Results were slightly more positive when comparing to populations of cancer patients; Tan et al. found no significant difference at a mean of 10 months post-operatively, whereas Chia et al. concluded that CRS/HIPEC patients had higher social functioning than other cancer patients on EORTC QLQ-C30 at a mean of 1.3 years post-operatively (62,64).

Functional and performance status

Assessment of a patient’s functional status following surgery overlaps somewhat with physical QOL and is treated differently by various instruments. For example, the SF-36 questionnaire assesses limitations in common activities and includes these in the score for patients’ physical functioning. The FACT scale instead separates functional well-being into a category distinct from physical well-being, focusing on a patient’s ability and satisfaction in their return to normal activities. Studies employing FACT or ECOG tended to report functional QOL separately from physical QOL, though with similar findings.

Using FACT-C, multiple groups showed that patients were able to regain baseline functional well-being by 6–12 months post-operatively (51,52,57,58). They each showed decreases in functional well-being on initial post-operative evaluations with McQuellon et al., in a 2001 paper, notably showing severe limitations in functional well-being at 2 weeks after surgery (46). For survivors at 1 year post-operatively, there was evidence from both Tuttle et al. and McQuellon et al., in a 2007 paper, that functional well-being increases above baseline levels (48,49).

Long-term survivors are not uniformly able to return to their normal activities, even up to several years after their operation. By example, Hill et al. found that only 47% of patients were able to return to normal activities at 12 months (54). Longer term cross-sectional analyses were slightly more positive; McQuellon et al., in a 2003 paper including 17 patients, showed that 88% had a score of 0 on the ECOG scale, with functional well-being improved at a mean of 5.3 years post-operatively compared to baseline surveys at 6 months (43). Despite this high functional status based on ECOG and FACT, the same study found that only 47% of patients had returned to work with another 24% on disability. Kirby et al. showed a considerably higher percentage of patients returning to work with 90% returned at a median follow-up of 31 months, though this study only included patients with PMP (63). Studies including more aggressive pathologies suggested higher rates of long-term disability. Duckworth et al. notably found that 45% and 84% of patients were limited in moderate or vigorous activity, respectively, at a mean of 4.2 years post-operatively (41). While many patients recover to pre-operative performance status within a year after surgery, there is ample evidence that others experience enduring functional limitations.

Pain and other somatic symptoms

Post-operative CRS/HIPEC patients experience a constellation of frequent symptoms both prior to and after surgery. Abdominal pain and gastrointestinal symptoms such as anorexia, nausea, constipation, and diarrhea are frequent, as are constitutional symptoms like fatigue and insomnia. The impact that surgery has on these symptoms is variable. Multiple prospective studies have shown that pain, typically assessed using the BPI, improves post-operatively after an initial worsening. Hill et al. and Tsilimparis et al. both found that pain increased initially after surgery before returning to baseline levels. McQuellon et al. concluded in 2007 that pain actually improves from baseline levels at 12 months, with only 8% of patients reporting intense pain compared to 17% pre-operatively (49,54,55). This improvement may be dependent on the success of the operation, as Alves et al. showed that only patients with a complete cytoreduction experienced improvement in pain; those undergoing debulking only experienced no relief (53).

Other somatic symptoms appeared to be more persistent in long-term survivors. Despite finding that pain improves to baseline levels, Tsilimparis et al. showed that fatigue, dyspnea, insomnia, and diarrhea all remain frequent in long-term survivors (55). This mirrors the findings of Schmidt et al. that patients have high rates of constipation and diarrhea relative to the general population despite having comparable pain levels (60). Fatigue and insomnia were particularly common in survivors. Tan et al. showed that CRS/HIPEC patients at a mean of 10 months post-operatively experience higher rates of fatigue than a reference population of cancer patients, and Kirby et al. estimate that 27% of CRS/HIPEC patients with PMP experience significant fatigue at a median of 31 months following surgery (62,63). This may be related to insomnia, as Duckworth et al. found that 56% of patients with multiple pathologies continue to experience insomnia at a mean follow-up of 4.2 years (41). Lastly, sexual dysfunction was infrequently evaluated but may be prevalent in long-term patients; Zenasni et al. found that 77% of patients reported issues with sexual function at a median follow-up of 2.4 years after surgery (61). Altogether, these findings show that multiple symptoms may decrease in the first year after surgery but remain prevalent in long-term survivors.

Summary

In this review of 27 published articles on QOL after CRS/HIPEC, several trends in the literature became clear. In the majority of studies, global QOL decreases acutely post-operatively with an eventual return to baseline at approximately 6–12 months. This improvement appears to be sustained in long-term survivors. When examining the domains of QOL individually, both physical and functional QOL mirrored this trend in global QOL with an acute decline post-operatively followed by recovery to baseline levels at 6–12 months. Some functional limitations persist, but many long-term survivors are able to return to normal activities. Social QOL was often diminished post-operatively as well, though less dramatically, and the time interval to regain baseline social QOL tended to be 12 months or longer. Emotional QOL was the least affected of all domains with many studies actually showing improvements from baseline emotional QOL post-operatively; persistent depression was an issue in long-term survivors, however. Regarding somatic symptoms, patients were generally observed to have less pain post-operatively, but other gastrointestinal and constitutional symptoms remained prevalent.

As utilization of CRS/HIPEC continues to increase across various histologies, the emphasis on post-operative QOL at different timepoints will only grow in importance. Early cohorts of CRS/HIPEC patients suffered from limited life expectancy, as evidenced by the significant attrition in the earliest studies reviewed here. However, there have been major improvements for several subsets of patients. By example, those with PMP secondary to low-grade appendiceal mucinous neoplasms (LAMNs) can expect a median survival of approximately 20 years after a successful cytoreduction (66). Survival benefits are more limited in the treatment of more aggressive, high-grade neoplasms; despite also arising from the appendix, appendiceal adenocarcinoma has a median overall survival of 91 months, decreasing to only 32 months with the presence of high-risk signet ring cells (67). Aggressive neoplasms from other sites in the abdomen have similar or shorter expected survival, but the overall trend in survival after CRS/HIPEC has been incremental improvement. Cross-sectional studies of long-term survivors offer some insight on longitudinal QOL concerns, but overall the existing literature on QOL after CRS/HIPEC is heavily weighted towards the first 12 months after surgery. As the number of long-term survivors following CRS/HIPEC continues to grow, further studies will be necessary to better characterize this population’s QOL and identify their needs. Improved understanding of this population will be essential for the successful implementation of survivorship programs and resources at CRS/HIPEC centers.

To maintain improvements in QOL, these programs should focus on interventions that have been shown to improve QOL in post-operative cancer patients. Patient education, psychological counseling, exercise programs, and cognitive therapy have all been shown to be effective in improving post-operative QOL in various cancer populations (68-70). Some somatic symptoms such as fatigue and insomnia may be improved by these programs, while others would likely benefit from pharmacologic interventions, Gastrointestinal symptoms are particularly prevalent and can be addressed with patient-tailored regimens of laxatives, pro-motility agents, and anti-diarrheal agents. Depression, a similarly prevalent symptom in post-operative patients, is often treated by a combination of anti-depressant therapy, neurostimulation, and psychiatric counseling (71). Pre-operative psychiatric “prehabilitation” programs may also play an important role in decreasing rates of depression in future patients (72).

Benefits from the development of these programs and resources would not be limited to long-term survivors. An equally important area for improvement is the first several months post-operatively, which remain less well understood despite significant fluctuations in QOL (73). This was the period associated with the most dramatic decrease in QOL across nearly all studies, yet it is the least well-studied. Of the 27 papers reviewed here, only eight assessed QOL prior to 3 months post-operatively. This lack of published data focusing on QOL in the immediate post-operative period potentially limits the ability of physicians to design protocols that treat and preempt frequent issues. It is not clear why there is a lack of data in the first 3 months after surgery, but to better address the symptoms that patients face following surgery, this critical period requires further attention. Continued study of the patient experience both in this acute post-operative period and in the period following 1 to 2 years post-operatively will ensure that increases in longevity are matched by improvements in QOL.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at http://dx.doi.org/10.21037/dmr-20-153

Peer Review File: Available at http://dx.doi.org/10.21037/dmr-20-153

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/dmr-20-153). OSE serves as an unpaid editorial board member of Digestive Medicine Research from Aug 2020 to Jul 2022. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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