For many patients with a primary visceral or peritoneal malignancy, the discovery of evidence of spread to the peritoneal surfaces represents a critical decision point in care. In well-selected patients with acceptable disease burden, multimodality treatment of cytoreductive surgery and heated intraperitoneal chemotherapy (CS/HIPEC) may offer extended survival compared with standard systemic chemotherapy or no treatment. CS/HIPEC for peritoneal disease has been available since the mid 1990s, and its efficacy in various primary malignancies has been demonstrated.1–7 However, given the perceived and real morbidities, its widespread acceptance, adoption, and accessibility remains a challenge by even recent inquiry.8,9

A continued area of focus among surgeons practicing CS/HIPEC procedures is refinement of patient selection and optimization prior to surgery. A recent systematic review suggested that morbidity and mortality rates are comparable to other major gastrointestinal surgical procedures in appropriate patients, with particular reference to outcomes of high-volume centers.10 There is a significant learning curve, and lack of homogeneity in protocols among centers has been a criticism levied at the procedure.11–13 Standardization in one country has led to improved patient selection, decreased morbidity, and better completeness of cytoreduction.14 Thus, teams undertaking this treatment modality may benefit from dissemination of information within the CS/HIPEC surgical community, participating in a “global learning curve.”.15,16

The American Society of Peritoneal Surface Malignancies (ASPSM) was created to develop guidelines regarding patient selection and standardization of therapies, with an aim to optimize benefit and minimize morbidity and overtreatment of this group of patients.17 In 2014, the ASPSM published recommendations to standardize CS/HIPEC delivery for colorectal cancer in the United States.18 Although based on consensus through a Delphi process rather than level I evidence, these recommendations demonstrated an interest by CS/HIPEC surgeons to standardize practices to facilitate comparisons of outcomes between practitioners and improve patient care.

The Enhanced Recovery After Surgery (ERAS®) Society guidelines have been shown to improve recovery and outcomes for many complex surgical procedures, including gastrectomy, pancreaticoduodenectomy, and colorectal and pelvic surgery.19 While the extent of cytoreduction is variable and individualized, CS/HIPEC patients may benefit from a streamlined protocol-driven approach as evidenced by the Dutch experience.14 Furthermore, as outlined in the recent American Society of Clinical Oncology Policy Statement on Clinical Pathways in Oncology, oncology pathways are detailed, evidence-based treatment protocols and should address the full spectrum of cancer care; pathways offer significant potential to improve the quality of patient care and to promote value.20

This study was designed to determine, in this complex, heterogeneous patient population with unique technical and physiological challenges of the procedure, which ERAS-based principles CS/HIPEC surgeons are currently embracing, and in what areas opportunities for improvement exist.

Methods

Study Population

Current members of the ASPSM who self-identified as a surgeon performing CS/HIPEC at a high-volume center (defined as >10 procedures performed/year) were invited to participate. High-volume centers were chosen with the intent to capture practices of established programs most likely to have streamlined or standardized care pathways. At present, there is lacking an accepted or published definition of “high-volume center” and the above metric was chosen by consensus of the authors.

Survey Construction

An English-language survey was developed by the authors and made available for anonymous submission online using a web-based survey service (SurveyMonkey Inc., Palo Alto, CA). The full survey is available in Appendix 1.

Survey Administration

Surgeons were requested by email to complete the survey within a 4-week period, with reminder emails sent at 2 and 3 weeks.21 Paper copies were available by request. The survey was not incentivized. Approval was obtained from the primary site Institutional Review Board.

Data Analysis

Data analysis was undertaken following survey closure. Data were summarized using descriptive statistics. Only surveys that were 80% complete were analyzed.

Results

Email invitations were sent to 177 ASPSM members; 97 self-identified as high-volume surgeons and completed the survey, a response rate of 55%. Response rates to individual questions averaged 87% (range 76–100%).

Demographics and Practice Details

Demographic and practice details of respondents are listed in Table 1. A wide geographic representation was secured from at least four continents. Most surgeons were younger than 49 years (68%). While the majority was in practice for longer than 10 years (68%), most had been performing CS/HIPEC for only the previous 5 (28%) or 10 years (34%). Approximately half the surgeons practiced in an academic setting associated with a cancer center (52%). Most had a foundation in general surgery (66%) with additional formal fellowship training in surgical oncology (68%), whereas 30% described experiences of shorter duration, in the form of apprenticeship/mentorship models with established CS/HIPEC surgeons.

Table 1 Demographics and practice details
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With regard to current practice patterns, most surgeons worked within a group of 3 other CS/HIPEC surgeons (37%), whereas 22% of surgeons were the sole practitioners performing CS/HIPEC at their center. Respondents reported performing a median 25 procedures per year in their own practice (range 1–150). Surgeons endorsed most experience in performing CS/HIPEC for appendiceal mucinous neoplasm and adenocarcinoma (99 and 93%, respectively), colorectal adenocarcinoma (96%), and primary peritoneal and ovarian malignancy (88 and 73%, respectively).

Preoperative Preparation

Most surgeons (68%) used a formalized preoperative pathway to prepare their patients for CS/HIPEC surgery, most commonly including provision of written material (Table 2). Fewer surgeons directed patients to web-based information (32%) or social media platforms.

Table 2 Preoperative preparation
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A majority of surgeons routinely administered mechanical bowel preparation, such as enemas or oral solutions (81%). Most did not routinely order nutritional supplements (59%).

Intraoperative Strategies, Techniques, Preferences

More than half of surgeons described performing CS/HIPEC with a closed system (59%; Table 3). A goal perfusion temperature of 42 °C was the most consistent choice (range 37–45 °C). While protocols varied, the most common agent selected was mitomycin C for a 90-min perfusion period (51% of respondents).

Table 3 Intraoperative practices
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In regard to the technical aspects of cytoreduction, distinct preferences were noted. Approximately two-thirds of surgeons favored stapled bowel anastomoses, whereas the rest preferred to hand-sew. Approximately half the surgeons routinely performed proximal diversion (ileostomy) in patients undergoing left-sided or multiple anastomoses. Lesser omentectomy was not a universal practice; only 53% of surgeons routinely performed it. Most surgeons reported regularly leaving a nasogastric tube (83%).

Considering anaesthetic management, the most common means of monitoring intraoperative volume status included central venous line (71%), urine output (95%), and heart rate and blood pressure parameters (86%). Fewer surgeons used devices such as esophageal Doppler (17%) or FloTrac/Vigileo™ (32%). A majority of surgeons used epidural anaesthesia/analgesia (89%), and there was some adoption of regional peripheral blocks (25%), such as transversus abdominis plane (TAP) blocks or commercially available catheter pumps.

Postoperative Strategies

A majority of surgeons admitted CS/HIPEC patients to the intensive care unit postoperatively (72%; Table 4).

Table 4 Postoperative care preferences
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Preferred means of fluid status and hemodynamic management in the early postoperative period varied among respondents. Most surgeons did not have a standardized protocol in place for management of hypotension (72%). Routine use of nonpacked red blood cell colloids (e.g., albumin, fresh frozen plasma, hydroxyethyl starch) was not widespread; only 39% administered these as part of postoperative volume replacement. Blood transfusion triggers were variable; 28% of respondents stated that their practice depended on the clinical picture. Whereas 36% of surgeons looked for evidence of end-organ hypoperfusion (e.g., cardiac symptoms, renal failure) as triggers for adding vasopressor/inotropic support to fluid resuscitation, 30% relied on information from continual pulse-wave analysis monitoring (FloTrac/Vigileo™).

Although 74% of respondents reported using ERAS principles with their CS/HIPEC patients, there was mixed adoption of features of this program. Most surgeons embraced early ambulation, with a majority encouraging patients to be out of bed by postoperative days 1 or 2 (74%). There was no consensus on triggers for nasogastric tube removal; when asked to select any/all parameters that must be met, 54% of surgeons reported waiting for return of bowel function (flatus or bowel movement), 43% used a cue of decreasing output volume, and 24% looked for a change in output character (bilious vs. clear). Sixteen percent routinely removed the tube on a prespecified postoperative day.

In the postoperative period, just over half of respondents used prophylactic antibiotics (51%), and a majority administered proton pump inhibitors (85%). Analgesia was accomplished using a combination of regional and parenteral approaches: epidural/spinal analgesia (78%), intravenous opioids (64%), nonsteroidal anti-inflammatory medications (40%), and acetaminophen (33%). Fewer surgeons routinely used peripheral blocks such as TAP blocks (14%), and only 5% employed ice packs for local pain relief.

Most surgeons ordered daily routine lab work in the initial postoperative period; some continued it during the admission (56%) and others discontinued once stabilization had occurred (38%). Some respondents offered specific schedules on the basis of an anticipated chemotherapy-related leucocyte/thrombocyte nadir.

Nutritional support was routinely supplemented postoperatively by 59% of surgeons, most commonly with TPN (78%), commercially available oral products (36%), or multivitamins (22%).

Many surgeons discharged patients with resources, including home nursing care (57%), home physiotherapy (43%), dietician follow-up (45%), and nutritional supports (49%). Prescribing a limited postoperative course (<30 day) of venous thromboembolism prophylaxis was a common though not a universal practice (62%).

Discussion

Although CS/HIPEC has been performed since the 1970s, there has been an increase in the number of these procedures during the past 5–10 years; most surgeons adopted the technique in that time period. Despite becoming widespread in practice, CS/HIPEC continues to be perceived by a sizable proportion of the surgical community as experimental, possibly related to lack of inclusion in clinical practice guidelines.22,23 Interestingly, recent evaluation of CS/HIPEC patient series suggest that morbidity, such as major complications or prolonged ICU stay, do not impinge on quality of life at 6 months postprocedure, or long-term survival.24,25 However, one of the persistent challenges to the acceptance of CS/HIPEC is the lack of consensus on appropriate indications and the inconsistency in technical practices, both of which serve to raise doubt as to its true efficacy.

In our survey, we characterized existing practices both within and outside the operating room to establish a baseline from which standardization of perioperative care can proceed. While we identified wide variability in practice in some aspects of the care process, others were more homogeneous across participants. Interestingly, components of intraoperative care in particular appeared fairly consistent in our sample, especially among U.S.-based surgeons. It is possible that the availability of the ASPSM recommendations have contributed to this consistency.

The existing framework in which most CS/HIPEC surgeons practice lends itself to regulation and quality improvement. Most surgeons in our sample operated in an academic setting or in affiliation with a cancer center, which implies an environment of institutional and cultural support for standards of acceptable practice. At this time, there is a lack of accepted regulation of either individuals or institutions for providing this type of procedure and care of CS/HIPEC patients, and there is a significant learning curve for optimization of both operative and oncologic outcomes.26 In this context, the establishment of universally accepted standard protocols for patient selection, preparation and prehabilitation, safe and effective intraoperative practice, and perioperative management is especially critical.

Most surgeons reported use of a formalized preoperative pathway at their site, most commonly in the form of provision of printed educational material or direction to websites. There remains a significant opportunity to educate and support patients as they make decisions about their care and prepare for complex surgery and to explore alternative routes of information delivery and patient connection such as social media. Recent review has suggested that psychological interventions or prehabilitation have potential to improve patient-reported outcome measures, such as quality of life, somatic symptoms, and psychological outcomes.27

Considerable variation existed in those surveyed with regard to practices of nutritional optimization and intraoperative decisions that may have implications for postoperative recovery. For example, although data suggest that the practice of feeding tube placement at time of CS/HIPEC is associated with increased readmission rates and longer length of stay, consensus was not clear in our sample.28 Also, surgeons were selective in choosing to perform diverting ileostomy or lesser omentectomy; both practices have potential impact on postoperative recovery with regard to delayed gastric emptying, resumption of enteral nutrition, fluid status, and need for a subsequent reversal procedure in the former. This suggests that there may be a need and interest for randomized studies of these practices.

Creating a consensus-based postoperative pathway for CS/HIPEC patients is possible with inclusion of evidence-based practices. Surgeons varied considerably in their approach to intraoperative fluid status monitoring and management, postoperative analgesia, and resources on discharge. Some practices, such as the routine use of postoperative antibiotics, proton pump inhibitors, and mechanical bowel preparation, do not have clear support in the literature, and their role in CS/HIPEC patients has not been specifically investigated. On the other hand, there is reasonable and accumulating support for interventions, such as extended thromboembolic prophylaxis.29 Even in the absence of level I evidence to support any particular practice, achieving consensus on perioperative care pathways can help surgeons to deliver care to their patients.

This study represents the first characterization of a large sample of high-volume CS/HIPEC surgeons’ perioperative and intraoperative practices. Strengths include an excellent response rate and completion rate achieved among motivated members who self-identify as high-volume surgeons. As such, the results are representative of current practices and beliefs as applicable to the majority of patients undergoing the procedure at this time.

Limitations of this study include the potential for self-report bias, and the fact that the ASPSM survey does not capture all CS/HIPEC sites across the world as the survey was not distributed to nonmembers. Due to survey design limitations, data were collected with regard to practice patterns without the benefit of rationale from the responding surgeon. Furthermore, resource availability (e.g., access to a step-down unit) and regional variation in the involvement of collaborating physicians (e.g., anaesthetists) may underlie the choice of various practices and represents a practical challenge to standardization of care for these patients.

We have identified key gaps in standardization of patient selection and preparation, intraoperative practices, and postoperative care patterns. This provides the foundation for development of standardized pathways. Moving forward in the field, these results may provide some basis for quality measures and benchmarking between programs (such as high and lower-volume centers) to assess alignment with common or accepted practices. As more patients are treated with CS/HIPEC, by more surgeons and more centers for broadening indications, it is appropriate timing to ensure that delivery of this care is guided by the cumulative experiences and evidence available in a streamlined approach for best surgical and oncologic outcomes.

Conclusions

Peri- and intraoperative care practices for patients undergoing CS/HIPEC by high-volume surgeons are widely variable. Standardization of such practices offers an opportunity to incorporate evidence-based interventions and may enhance patient outcomes and improve care standards across all centers that offer this procedure.