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A clinical pathway for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for advanced ovarian and primary peritoneal cancers
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Gynecologic Oncology 108 (2008) 282 – 286 www.elsevier.com/locate/ygyno
A clinical pathway for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for advanced ovarian and primary peritoneal cancers Melissa A. Gerardi a , Antonio Santillan a , Benjamin Meisner a , Marianna L. Zahurak b , Teresa P. Diaz Montes a , Robert L. Giuntoli II a , Robert E. Bristow a,c,⁎ a
The Kelly Gynecologic Oncology Service, Department of Obstetrics and Gynecology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA b Department of Biostatistics, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA c Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Received 10 July 2007 Available online 19 November 2007
Abstract Objectives. To evaluate the safety, feasibility, and economic impact of a clinical pathway, including rapid diet advancement, for patients undergoing rectosigmoid colectomy as part of cytoreductive surgery for advanced ovarian and primary peritoneal cancers. Methods. Between 8/1/98 and 6/30/06, 64 consecutive patients met study inclusion criteria. Using case–control methodology, post-operative management was dictated by a prescribed clinical pathway in 19 patients (Group A) and directed by individual surgeon preference in 45 patients (Group B). Critical elements of the clinical pathway included: rapid diet advancement, early discontinuance of nasogastric suction, criteria-based utilization of parenteral nutrition, selective laboratory testing, and deferring initiation of chemotherapy until after discharge. Results. Stage IIIC/IV disease was present in 94% of all patients. The median time to flatus was 6 days for both groups ( p = 0.95); however, the median time to tolerance of diet was 3 days for Group A and 6 days for Group B ( p = 0.013). Compared to Group B, patients in Group A had a significantly shorter median length of hospital stay (7 days vs 10 days, p = 0.014) and lower median 30-day post-operative hospital cost ($19,700 vs $25,110, p = 0.028), with no significant difference in 30-day readmission rate (21% vs 33%, p = 0.379). Clinical pathway-directed management was associated with a median reduction in hospital cost of $5410 per patient. Conclusions. A critical pathway incorporating rapid diet advancement for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for ovarian and primary peritoneal cancers is feasible, safe, and associated with a significant reduction in length of hospital stay and hospital-related costs. © 2007 Elsevier Inc. All rights reserved. Keywords: Ovarian cancer; Rectosigmoid colectomy; Clinical pathway
Introduction Clinical pathways, also known as critical pathways, are management plans that delineate specific clinical care goals for patients and provide the sequence and timing of actions necessary to achieve these goals with optimal efficiency. While the ⁎ Corresponding author. The Kelly Gynecologic Oncology Service, Department of Obstetrics and Gynecology, 600 North Wolfe Street, Phipps #281, Baltimore, MD 21287, USA. Fax: +1 410 614 8718. E-mail address: [email protected] (R.E. Bristow). 0090-8258/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2007.10.014
physician must remain alert to deviations from the expected course of events, the use of the clinical pathway can bring greater predictability to the entire treatment process. In addition to reducing the overutilization of resources and decreased length of hospital stay, prescribed pathways have been shown to improve the quality of care [1]. Post-operative clinical pathways in colorectal surgery have been associated with a decreased length of hospital stay and hospital charges, without compromising patient satisfaction or care [2]. This is largely attributable to early oral feeding, which has demonstrated overall safety and tolerability in patients undergoing bowel resections
M.A. Gerardi et al. / Gynecologic Oncology 108 (2008) 282–286
[3]. In a recent systematic review of the literature, Ng and Neill concluded that there was no obvious benefit for keeping patients “nil per mouth” after gastrointestinal surgery [4]. The role of early post-operative feeding in gynecologic oncology patients undergoing gastrointestinal surgery has not been fully established. Ghosh et al. demonstrated that critical pathways including early feeding in gynecologic oncology patients undergoing hysterectomy could be implemented in order to maintain high quality of care and reduce hospital costs, while providing positive patient outcomes [5]. However, the potential impact of rapid diet advancement on patients undergoing primary cytoreductive surgery with rectosigmoid colectomy (radical oophorectomy) for advanced ovarian or primary peritoneal cancer is unknown. For the purposes of this study, rectosigmoid colectomy was defined as an en bloc resection of the internal gynecologic viscera (ovaries, fallopian tubes, and uterus, if present) and rectosigmoid colon with pan-pelvic peritonectomy [6]. The goal of this case–control study was to evaluate the overall safety, feasibility, and economic impact of a clinical pathway that included rapid diet advancement in this patient population. Methods The study methodology was that of a case–control investigation. Between August 1, 1998 and June 30, 2006, all patients with International Federation of Gynecology and Obstetrics (FIGO) Stages II–IV epithelial ovarian or primary peritoneal cancer undergoing primary cytoreductive surgery at the Johns Hopkins Medical Institutions (JHMI) were identified from the institutional tumor registry database and screened retrospectively for patient demographics at the time of primary surgical treatment. Following initial eligibility screening, the following inclusion criteria were applied: (1) a diagnosis of epithelial ovarian or primary peritoneal cancer rendered by an attending gynecologic pathologist; (2) radical oophorectomy with primary colorectal anastomosis as part of the initial maximal cytoreductive surgical effort; (3) a minimum of 30 days postoperative course follow-up information. Cases were defined as all consecutive patients meeting inclusion criteria that were prospectively identified as having their post-operative management dictated according to a clinical pathway for early oral feeding that was implemented on our service July 1, 2005 (Group A). The essential elements of clinical management dictated by the clinical pathway included: (1) rapid diet advancement to clear liquids prior to passage of flatus and no later than post-operative day 3, as permitted by mechanical ventilation status, (2) rapid discontinuance of nasogastric tube (NGT) suction prior to passage of flatus and no later than post-operative day 3, as permitted by mechanical ventilation status, (3) initiation of total parenteral nutrition (TPN) only if the pre-operative serum albumin level was ≤2.0 g/dl and/or resumption of oral intake was anticipated to be delayed for ≥7 days postoperatively, and (4) selective use of post-operative laboratory testing based on documented electrolyte, chemistry, or hematologic abnormalities. Controls were identified as consecutive patients meeting all inclusion criteria that were treated between August 1, 1998 and June 30, 2005, prior to instituting the rapid diet advancement clinical pathway (Group B). For control patients, post-operative management was dictated exclusively by the preferences of the attending surgeon. During the entire study period, anti-emetic regimens were similar for patients in both Group A and Group B and consisted of select serotonin receptor antagonists (5-HT3), phenothiazines, and dopamine antagonists to control postoperative nausea and vomiting. Pain control regimens were also similar for both groups and consisted of narcotic epidural and/or intravenous patient controlled analgesia (PCA). The narcotics utilized in the PCA pumps were morphine sulfate, fentanyl or hydromorphone solutions. Clinical data were abstracted retrospectively from the in-patient medical record and included information on: demographic characteristics, intraoperative parameters, post-operative course (intensive care unit admission days, days to passage of flatus, days to initiation of diet, utilization of NGT, administration of post-operative chemotherapy, days to tolerance of diet, post-operative compli-
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cations, length of hospital stay, and hospital readmission rate), and total direct and indirect hospital costs for a 30-day window beginning with the date of primary cytoreductive surgery. Post-operative complications occurring within 30 days of surgery and meeting Gynecologic Oncology Group criteria for grade 2–4 severity were also recorded. The primary outcome measures were the presence or absence of statistically significant differences between Group A and Group B along the following parameters: age at surgery, FIGO stage distribution, estimated operative blood loss, the proportion of patients undergoing bowel resection in addition to rectosigmoid colectomy, time to tolerance of oral (PO) intake (in days), time to passage of flatus (in days), length of intensive care unit (ICU) stay (in days), incidence of Gynecologic Oncology Group grade 2–4 post-operative morbidity, chemotherapy administration prior to hospital discharge, total duration of hospital stay (LOS, in days), 30-day hospital readmission rate, and total hospital costs (in US dollars). Hospital costs included the total direct and indirect costs of post-operative care per patient (less the cost of chemotherapy, when indicated) and were calculated for both their primary hospital stay and readmission occurring within 30 days of initial surgery. The cost of post-operative intravenous chemotherapy was omitted since this is thought to be an inevitable cost as it is considered a standard in the treatment of the patients included in this study. All hospital costs were adjusted to 2006 US dollars using the consumer price index. Power analysis indicated that at least 15 subjects in group would be necessary to have 80% power to detect a 20% difference in total post-operative hospital costs. For statistical analysis, two tailed unpaired Student's t-test and the Mann– Whitney test were used to compare parametric data, and chi-square test was used to evaluate for proportional differences between Group A and Group B. In addition to the univariate analyses described above, multivariate linear regression analyses were performed for the main clinical and economic parameters of total length of hospital stay and total hospital costs in order to identify statistically significant and independent predictors of these clinical outcomes. All p values reported are two-sided. Statistical significance was defined as p values less than 0.05. Computations were performed using Statistical Analysis System (SAS Institute, Cary, North Carolina) or EGRET software [7,8].
Results Sixty-four patients satisfied inclusion criteria. Nineteen patients were enrolled during the clinical pathway implementation period (Group A), and 45 patients were identified as being treated prior to the implementation of the clinical pathway (Group B). Ninety-four percent of patients had FIGO stage IIIC/ IV disease. Clinical and economic parameters for patients in Group A and Group B are shown in Table 1. All patients in Group A had indwelling NGTs placed that were removed a median of 2.0 days (mean = 3.1 days) post-operatively, with the exception of one patient, who had prolonged NGT intubation secondary to an extended ICU stay and requirement for airway intubation with mechanical ventilation. Eighteen of nineteen patients (94.7%) in Group A tolerated clear liquids when initially advanced. One patient could not tolerate her diet secondary to adynamic ileus and had a NGT replaced on post-operative day number nine. However, this patient was able to tolerate regular diet upon discharge (post-operative day 18). In Group B, 41 patients (91%) had indwelling NGTs after surgery, which were discontinued a median of 3.0 days (mean = 4.1 days) postoperatively. Diet advancement was started only when patients had passage of flatus. Five patients (11.1%) were not able to tolerate clear liquids upon diet advancement and one patient (2.2%) was never advanced secondary to prolonged adynamic ileus and was discharged home on TPN. There were no statistically significant differences between Group A and Group B with respect to age at surgery, FIGO
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Table 1 Comparison of clinical and economic parameters between implementation group (A) (n = 19) and control group (B) (n = 45) Group A
Group B
Age at surgery (years) Median 67 58 Mean 62 58 Range 36–83 22–85 FIGO stage of disease Stage II 5.3% 2.2% Stage III 73.7% 66.7% Stage IV 21.0% 31.1% Estimated blood loss (cubic centimeters) Median 1400 900 Mean 1536 1205 Range 500–4250 200–5250 Bowel resection in addition to rectosigmoid colectomy Yes 42.1% 42.2% No 57.9% 57.8% Administration of post-operative TPN Yes 26.3% 68.9% No 73.7% 31.1% Tolerance of PO intake (days) Median 3.0 6.0 Mean 4.5 6.1 Range 1–20 1–14 Flatus-post-op (days) Median 6.0 6.0 Mean 6.8 6.9 Range 4–20 2–15 ICU stay (days) Median 2.0 2.0 Mean 2.8 3.2 Range 0–16 0–24 Grade 2–4 post-operative complications Yes 57.9% 62.2% No 42.1% 37.8% Chemotherapy prior to discharge Yes 5.3% 31.1% No 94.7% 68.9% Length of Stay (days) Median 7.0 10.0 Mean 8.7 11.4 Range 3–27 5–30 Readmission within 30 days of discharge Yes 21.1% 33.3% No 78.9% 66.7% Hospital cost (2006 US dollars) Median 19,700 25,110 Mean 23,912 30,205 Range 11,010–84,170 11,980–78,150
Significance (p-value) 0.248⁎
0.615⁎
0.072⁎
0.993⁎ 0.017⁎ 0.013⁎
0.630⁎
0.702⁎
0.746⁎ 0.026⁎ 0.010†
(5.3%) life-threatening post-operative complication in Group A, requiring multiple surgical interventions for abdominal compartment syndrome. There were no anastomotic breakdowns or fistulas associated with this group. The most common complications in Group B were wound infections, adynamic ileus, pelvic abscess, fever, and pelvic hematoma. Two patients (4.4%) in Group B required repeat operative intervention. One patient required re-exploration on post-operative day 13 for a pelvic abscess. The other patient had a superficial abdominal wound separation, requiring secondary closure on post-operative day 11. There was one entero-vaginal fistula, which was managed conservatively and healed spontaneously. One patient in Group B was readmitted on post-operative day 29 secondary to neutropenic fever and sepsis following chemotherapy. The patient subsequently expired on day 17. This was the only postoperative mortality in either group. As shown in Table 1, patients in Group A were statistically significantly less likely to have received post-operative TPN and systemic chemotherapy prior to discharge. Patients in Group A tolerated oral intake a median of 3 days post-operatively, compared to a median of 6 days for patients in Group B, which was a statistically significant difference ( p = 0.013). Similarly, patients in Group A had a median total hospital LOS of 7.0 days, compared to a median LOS of 10.0 days for patients in Group B. This difference was statistically significant on both univariate and multivariate analysis. The median total hospital cost of postoperative care for patients in Group A was $19,700, compared to a median total cost of $25,110 for patients in Group B. Again, this difference was statistically significant on both univariate and multivariate analysis. The cost of intravenous chemotherapy administered prior to discharge was analyzed and demonstrated a median cost of $340 per patient treated. This did not change the statistical significance of the overall hospital costs. Overall, clinical pathway-directed management was associated with a median reduction in total direct and indirect hospital cost of postoperative care of $5410 per patient. Discussion
0.326⁎ 0.043†
FIGO: International Federation of Gynecology and Obstetrics. NGT: nasogastric tube. TPN: total parenteral nutrition. ⁎ univariate analysis. † multivariate analysis.
stage of disease, estimated operative blood loss, the proportion of patients undergoing bowel resection in addition to rectosigmoid colectomy, duration of NGT suction, time to first flatus, duration of ICU stay, incidence of grade 2–4 complications, and 30-day hospital readmission rate. The most common postoperative morbidities in Group A were fever, abscess, adynamic ileus, and Clostridium difficile colitis. There was only one
The American Cancer Society has estimated that 22,430 new cases of ovarian cancer will be diagnosed in the United States in 2007 with 15,280 disease-related deaths [9]. Most patients will present with FIGO Stage III or IV disease. The most powerful predictor of overall survival for these patients is optimal primary cytoreductive surgery followed by platinum and taxane based chemotherapy [10–13]. In order to achieve minimal residual disease, a significant proportion of patients will require extensive resection of pelvic viscera, including resection of the rectosigmoid with primary anastomosis. This procedure has been previously described as having acceptable associated morbidity [14–17]. A challenge that is encountered by the gynecologic oncologist caring for this select group of patients is the appropriate time to reintroduce oral intake. There has not been an established standard of care for early post-operative feeding in the gynecologic oncology population. Randomized controlled trials in gynecologic and gynecologic oncology patients undergoing major surgery have demonstrated that early feeding is
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feasible, well tolerated, and promotes a more rapid recovery compared to those treated conservatively [18,19]. A study by Marx et al. evaluated the effect of fast-track, multimodal rehabilitation in patients with ovarian malignancies and demonstrated an overall benefit with regard to hospital stay as well as medical morbidity [20]. However, there were only ten patients that were evaluated, and different types of colonic resections were performed. To date, there has not been an investigation specifically evaluating the safety and feasibility of rapid diet advancement in patients with advanced ovarian and primary peritoneal cancers undergoing optimal surgery with rectosigmoid resection. The practice of prolonged nasogastric intubation and withholding feeding until bowel function has resumed has been long established in many surgical practices. However, a number of studies have now demonstrated that this practice offers no overall benefit to patient care. Cutillo et al. reported that nasogastric decompression can actually delay the return to normal gastrointestinal function [21]. Post-operatively, gastric emptying function usually returns within 24 h, and colonic activity recovers within 48–72 h of abdominal surgery. Therefore, initiating a diet on post-operative day one or two should be safe and efficacious with regard to overall recovery. Initiating patients who have undergone abdominal or gynecologic procedures on a regular diet as opposed to a clear liquid diet has not been associated with an increase in gastrointestinal complaints [22,23]. Specifically from the colorectal cancer literature, Reismann et al. performed a prospective randomized trial and found that early feeding did not affect the duration of adynamic ileus, which was similar in both study groups [24]. In addition, Behrns et al. demonstrated that patients undergoing various intestinal procedures who were given a clear liquid diet by postoperative day number two were discharged from the hospital sooner than those managed conservatively [25]. The introduction of a clinical, or critical, pathway streamlines the post-operative care of surgical patients and places emphasis on improving cost reduction within a hospital system, presumably without increasing complication rate or readmission rate. One large study conducted by Melbert et al. looked at a specific critical pathway for 385 patients that underwent colorectal resections and concluded that the use of this pathway was statistically significant with regard to shortened lengths of hospital stay, earlier resumption to regular diet, and diminished hospital charges, with no diminution of patients' perceptions of satisfaction with the hospital experience [26]. These outcomes, along with the results of the current case–control study, support the application of a clinical pathway to patients undergoing rectosigmoid colectomy as part of primary cytoreductive surgery for advanced ovarian and peritoneal cancers. Although patients in Group A were older and their surgeries were associated with a higher estimated blood loss, there were no statistically significant differences in the rate of complications or incidence of hospital readmission with 30 days of initial surgery compared to Group B. Notably, patients in Group A tolerated a regular diet a median of 3.0 days earlier than patients in Group B. This finding, coupled with a statistically significant reduction in the proportion of patients receiving chemotherapy during the index admission, yielded a median reduction in the hospital
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LOS of 3.0 days compared to patients in Group B. Overall, management according the prescribed clinical pathway was the only statistically significant and independent predictor of postoperative hospital cost, with a median reduction of $5410 per patient in Group A. Although the administration of chemotherapy did impact on the overall length of stay, omitting the cost of chemotherapy during the primary admission did not demonstrate statistical significance with regard to hospital cost. There are two important limitations of the current study that must be considered in interpreting the results presented. First, the number of subjects in the experimental group (Group A) was relatively modest; however, the study was powered to detect a meaningful difference (20%) in hospital costs associated with management according to the clinical pathway. It is possible that with a larger number of subjects the magnitude of the observed differences in clinical and economic parameters could be less compelling. Second, the case–control study methodology was selected to evaluate the feasibility, safety, and potential economic impact of the prescribed clinical pathway among a homogenous group of patients over a relatively brief period of time. This methodology, however, may not have accounted for all potential factors that may have influenced the observed findings for the clinical and economic outcomes under study. Case–control studies may also be prone to recall bias; however, this risk was minimized by the prospective collection of data for patients in Group A and limiting the outcomes of interest to those parameters that could be objectively determined from the medical record. Despite these limitations, the results of the current study indicate that a critical pathway incorporating rapid diet advancement for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for advanced ovarian and primary peritoneal cancers appears feasible, safe, and is associated with a statistically significant reduction in the length of hospital stay and hospital-related costs. Ideally, this study will provide the basis for a larger, prospective, randomized, multi-institutional collaborative investigation to confirm or refute these initial observations. Acknowledgment This work supported by the Elizabeth Frost Ovarian Cancer Research Fund. References [1] Panella M, Marchisio S, Di Stanislao F. Reducing clinical variations with clinical pathways: do pathways work? Int J Qual Health Care 2003;6: 509–21. [2] Stephen AE, Berger DL. Shortened length of stay and hospital cost reduction with implementation of an accelerated clinical care pathway after elective colon resection. Surgery 2003;133(2):77–82. [3] Pritts TA, Nussbaum MS, Flesch LV, Fegelman EJ, Parikh AA, Fischer JE. Implementation of a clinical pathway decreases length of stay and cost for bowel resection. Ann Surg 1999;230:728–33. [4] Ng WQ, Neill J. Evidence for early oral feeding of patients after elective open colorectal surgery: a literature review. J Clin Nurs 2006;15(6):696–709. [5] Ghosh K, Downs LS, Padilla LA, Murray KP, Twiggs LB, Letourneau CM, et al. The implementation of critical pathways in gynecologic oncology in a managed care setting: a cost analysis. Gynecol Oncol 2001;83(2):378–82.
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[6] Bristow RE, del Carmen MG, Kaufman HS, Montz FJ. Radical oophorectomy with primary stapled colorectal anastomosis for resection of locally advanced epithelial ovarian cancer. J Am Coll Surg 2003;197: 565–774. [7] SAS Institute Inc. SAS User's Guide: Statistics, Version 5. Cary, NC: SAS Institute Inc; 1985. [8] Statistics and Epidemiology Research Corporation. EGRET User's Manual. Seattle, WA: Statistics and Epidemiology Research Corporation; 1988. [9] Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43–66. [10] Hoskins WJ, McGuire WP, Brady MF, et al. The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet Gynecol 1994;170:974–9. [11] Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 2002;20: 1248–59. [12] Chi DS, Eisenhauer EL, Lang J, Huh J, Haddad L, Abu-Rustum NR, et al. What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)? Gynecol Oncol 2006;103:559–64. [13] Aletti GD, Dowdy SC, Gostout BS, Jones MB, Stanhope CR, Wilson TO, et al. Aggressive surgical effort and improved survival in advanced-stage ovarian cancer. Obstet Gynecol 2006;107:77–85. [14] Eisenkop SM, Nalick RH, Teng NN. Modified posterior exenteration for ovarian cancer. Obstet Gynecol 1991;78:879–85. [15] Obermair A, Hagenauer S, Tamandl D, et al. Safety and efficacy of low anterior en bloc resection as part of cytoreductive surgery for patients with ovarian cancer. Gynecol Oncol 2001;83:115–20. [16] Mourton SM, Temple LK, Abu-Rustum NR, Gemignani ML, Sonoda Y, Bochner BH, et al. Morbidity of rectosigmoid resection and primary anastomosis in patients undergoing primary cytoreductive surgery for advanced epithelial ovarian cancer. Gynecol Oncol 2005;99:608–14.
[17] Berek JS, Hacker NF, Lagasse LD. Rectosigmoid colectomy and reanastomosis to facilitate resection of primary and recurrent gynecologic cancer. Obstet Gynecol Nov 1984;64(5):715–20. [18] Pearl ML, Valea FA, Fischer M, Mahler L, Chalas E. A randomized controlled trial of early postoperative feeding in gynecologic oncology patients undergoing intra-abdominal surgery. Obstet Gynecol 1998;92: 94–7. [19] Schilder JM, Hurteau JA, Look KY, Moore DH, Raff G, Stehman FB, et al. A prospective controlled trial of early postoperative oral intake following major abdominal gynecologic surgery. Gynecol Oncol 1997;67:235–40. [20] Marx C, Rasmussen T, Jakobsen DH, Ottosen C, Lundvall L, Ottesen B, et al. The effect of accelerated rehabilitation on recovery after surgery for ovarian malignancy. Acta Obstet Gynecol Scand 2006;85:488–92. [21] Cutillo G, Maneschi F, Franchi M, Giannice R, Scambia G, BenedettiPanici P. Early feeding compared with nasogastric decompression after major oncologic gynecologic surgery: a randomized study. Obstet Gynecol 1999;93:41–5. [22] MacMillan SL, Kammerer-Doak D, Rogers RG, Parker KM. Early feeding and the incidence of gastrointestinal symptoms after major gynecologic surgery. Obstet Gynecol 2000;96:604–8. [23] Steed HL, Capstick V, Flood C, Schepansky A, Schulz J, Mayes DC. A randomized controlled trial of early versus “ traditional” postoperative oral intake after major abdominal gynecologic surgery. Am J Obstect Gynecol 2002;186:861–5. [24] Reissman P, Teoh TA, Cohen SM, Weiss EG, Nogueras JJ, Wexner SD. Is early oral feeding safe after elective colorectal surgery? A prospective randomized trial. Ann Surg 1995;222:73–7. [25] Behrns KE, Kircher AP, Galanko JA, Brownstein MR, Koruda MJ. Prospective randomized trial of early initiation and hospital discharge on a liquid diet following elective intestinal surgery. J Gastrointest Surg 2000;4: 217–21. [26] Melbert RB, Kimmins MH, Isler JT, Billingham RP, Lawton D, Salvadalena G, et al. Use of a critical pathway for colon resections. J Gastrointest Surg 2002;6(5):745–52.
Gynecologic Oncology 108 (2008) 282 – 286 www.elsevier.com/locate/ygyno
A clinical pathway for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for advanced ovarian and primary peritoneal cancers Melissa A. Gerardi a , Antonio Santillan a , Benjamin Meisner a , Marianna L. Zahurak b , Teresa P. Diaz Montes a , Robert L. Giuntoli II a , Robert E. Bristow a,c,⁎ a
The Kelly Gynecologic Oncology Service, Department of Obstetrics and Gynecology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA b Department of Biostatistics, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA c Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA Received 10 July 2007 Available online 19 November 2007
Abstract Objectives. To evaluate the safety, feasibility, and economic impact of a clinical pathway, including rapid diet advancement, for patients undergoing rectosigmoid colectomy as part of cytoreductive surgery for advanced ovarian and primary peritoneal cancers. Methods. Between 8/1/98 and 6/30/06, 64 consecutive patients met study inclusion criteria. Using case–control methodology, post-operative management was dictated by a prescribed clinical pathway in 19 patients (Group A) and directed by individual surgeon preference in 45 patients (Group B). Critical elements of the clinical pathway included: rapid diet advancement, early discontinuance of nasogastric suction, criteria-based utilization of parenteral nutrition, selective laboratory testing, and deferring initiation of chemotherapy until after discharge. Results. Stage IIIC/IV disease was present in 94% of all patients. The median time to flatus was 6 days for both groups ( p = 0.95); however, the median time to tolerance of diet was 3 days for Group A and 6 days for Group B ( p = 0.013). Compared to Group B, patients in Group A had a significantly shorter median length of hospital stay (7 days vs 10 days, p = 0.014) and lower median 30-day post-operative hospital cost ($19,700 vs $25,110, p = 0.028), with no significant difference in 30-day readmission rate (21% vs 33%, p = 0.379). Clinical pathway-directed management was associated with a median reduction in hospital cost of $5410 per patient. Conclusions. A critical pathway incorporating rapid diet advancement for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for ovarian and primary peritoneal cancers is feasible, safe, and associated with a significant reduction in length of hospital stay and hospital-related costs. © 2007 Elsevier Inc. All rights reserved. Keywords: Ovarian cancer; Rectosigmoid colectomy; Clinical pathway
Introduction Clinical pathways, also known as critical pathways, are management plans that delineate specific clinical care goals for patients and provide the sequence and timing of actions necessary to achieve these goals with optimal efficiency. While the ⁎ Corresponding author. The Kelly Gynecologic Oncology Service, Department of Obstetrics and Gynecology, 600 North Wolfe Street, Phipps #281, Baltimore, MD 21287, USA. Fax: +1 410 614 8718. E-mail address: [email protected] (R.E. Bristow). 0090-8258/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2007.10.014
physician must remain alert to deviations from the expected course of events, the use of the clinical pathway can bring greater predictability to the entire treatment process. In addition to reducing the overutilization of resources and decreased length of hospital stay, prescribed pathways have been shown to improve the quality of care [1]. Post-operative clinical pathways in colorectal surgery have been associated with a decreased length of hospital stay and hospital charges, without compromising patient satisfaction or care [2]. This is largely attributable to early oral feeding, which has demonstrated overall safety and tolerability in patients undergoing bowel resections
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[3]. In a recent systematic review of the literature, Ng and Neill concluded that there was no obvious benefit for keeping patients “nil per mouth” after gastrointestinal surgery [4]. The role of early post-operative feeding in gynecologic oncology patients undergoing gastrointestinal surgery has not been fully established. Ghosh et al. demonstrated that critical pathways including early feeding in gynecologic oncology patients undergoing hysterectomy could be implemented in order to maintain high quality of care and reduce hospital costs, while providing positive patient outcomes [5]. However, the potential impact of rapid diet advancement on patients undergoing primary cytoreductive surgery with rectosigmoid colectomy (radical oophorectomy) for advanced ovarian or primary peritoneal cancer is unknown. For the purposes of this study, rectosigmoid colectomy was defined as an en bloc resection of the internal gynecologic viscera (ovaries, fallopian tubes, and uterus, if present) and rectosigmoid colon with pan-pelvic peritonectomy [6]. The goal of this case–control study was to evaluate the overall safety, feasibility, and economic impact of a clinical pathway that included rapid diet advancement in this patient population. Methods The study methodology was that of a case–control investigation. Between August 1, 1998 and June 30, 2006, all patients with International Federation of Gynecology and Obstetrics (FIGO) Stages II–IV epithelial ovarian or primary peritoneal cancer undergoing primary cytoreductive surgery at the Johns Hopkins Medical Institutions (JHMI) were identified from the institutional tumor registry database and screened retrospectively for patient demographics at the time of primary surgical treatment. Following initial eligibility screening, the following inclusion criteria were applied: (1) a diagnosis of epithelial ovarian or primary peritoneal cancer rendered by an attending gynecologic pathologist; (2) radical oophorectomy with primary colorectal anastomosis as part of the initial maximal cytoreductive surgical effort; (3) a minimum of 30 days postoperative course follow-up information. Cases were defined as all consecutive patients meeting inclusion criteria that were prospectively identified as having their post-operative management dictated according to a clinical pathway for early oral feeding that was implemented on our service July 1, 2005 (Group A). The essential elements of clinical management dictated by the clinical pathway included: (1) rapid diet advancement to clear liquids prior to passage of flatus and no later than post-operative day 3, as permitted by mechanical ventilation status, (2) rapid discontinuance of nasogastric tube (NGT) suction prior to passage of flatus and no later than post-operative day 3, as permitted by mechanical ventilation status, (3) initiation of total parenteral nutrition (TPN) only if the pre-operative serum albumin level was ≤2.0 g/dl and/or resumption of oral intake was anticipated to be delayed for ≥7 days postoperatively, and (4) selective use of post-operative laboratory testing based on documented electrolyte, chemistry, or hematologic abnormalities. Controls were identified as consecutive patients meeting all inclusion criteria that were treated between August 1, 1998 and June 30, 2005, prior to instituting the rapid diet advancement clinical pathway (Group B). For control patients, post-operative management was dictated exclusively by the preferences of the attending surgeon. During the entire study period, anti-emetic regimens were similar for patients in both Group A and Group B and consisted of select serotonin receptor antagonists (5-HT3), phenothiazines, and dopamine antagonists to control postoperative nausea and vomiting. Pain control regimens were also similar for both groups and consisted of narcotic epidural and/or intravenous patient controlled analgesia (PCA). The narcotics utilized in the PCA pumps were morphine sulfate, fentanyl or hydromorphone solutions. Clinical data were abstracted retrospectively from the in-patient medical record and included information on: demographic characteristics, intraoperative parameters, post-operative course (intensive care unit admission days, days to passage of flatus, days to initiation of diet, utilization of NGT, administration of post-operative chemotherapy, days to tolerance of diet, post-operative compli-
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cations, length of hospital stay, and hospital readmission rate), and total direct and indirect hospital costs for a 30-day window beginning with the date of primary cytoreductive surgery. Post-operative complications occurring within 30 days of surgery and meeting Gynecologic Oncology Group criteria for grade 2–4 severity were also recorded. The primary outcome measures were the presence or absence of statistically significant differences between Group A and Group B along the following parameters: age at surgery, FIGO stage distribution, estimated operative blood loss, the proportion of patients undergoing bowel resection in addition to rectosigmoid colectomy, time to tolerance of oral (PO) intake (in days), time to passage of flatus (in days), length of intensive care unit (ICU) stay (in days), incidence of Gynecologic Oncology Group grade 2–4 post-operative morbidity, chemotherapy administration prior to hospital discharge, total duration of hospital stay (LOS, in days), 30-day hospital readmission rate, and total hospital costs (in US dollars). Hospital costs included the total direct and indirect costs of post-operative care per patient (less the cost of chemotherapy, when indicated) and were calculated for both their primary hospital stay and readmission occurring within 30 days of initial surgery. The cost of post-operative intravenous chemotherapy was omitted since this is thought to be an inevitable cost as it is considered a standard in the treatment of the patients included in this study. All hospital costs were adjusted to 2006 US dollars using the consumer price index. Power analysis indicated that at least 15 subjects in group would be necessary to have 80% power to detect a 20% difference in total post-operative hospital costs. For statistical analysis, two tailed unpaired Student's t-test and the Mann– Whitney test were used to compare parametric data, and chi-square test was used to evaluate for proportional differences between Group A and Group B. In addition to the univariate analyses described above, multivariate linear regression analyses were performed for the main clinical and economic parameters of total length of hospital stay and total hospital costs in order to identify statistically significant and independent predictors of these clinical outcomes. All p values reported are two-sided. Statistical significance was defined as p values less than 0.05. Computations were performed using Statistical Analysis System (SAS Institute, Cary, North Carolina) or EGRET software [7,8].
Results Sixty-four patients satisfied inclusion criteria. Nineteen patients were enrolled during the clinical pathway implementation period (Group A), and 45 patients were identified as being treated prior to the implementation of the clinical pathway (Group B). Ninety-four percent of patients had FIGO stage IIIC/ IV disease. Clinical and economic parameters for patients in Group A and Group B are shown in Table 1. All patients in Group A had indwelling NGTs placed that were removed a median of 2.0 days (mean = 3.1 days) post-operatively, with the exception of one patient, who had prolonged NGT intubation secondary to an extended ICU stay and requirement for airway intubation with mechanical ventilation. Eighteen of nineteen patients (94.7%) in Group A tolerated clear liquids when initially advanced. One patient could not tolerate her diet secondary to adynamic ileus and had a NGT replaced on post-operative day number nine. However, this patient was able to tolerate regular diet upon discharge (post-operative day 18). In Group B, 41 patients (91%) had indwelling NGTs after surgery, which were discontinued a median of 3.0 days (mean = 4.1 days) postoperatively. Diet advancement was started only when patients had passage of flatus. Five patients (11.1%) were not able to tolerate clear liquids upon diet advancement and one patient (2.2%) was never advanced secondary to prolonged adynamic ileus and was discharged home on TPN. There were no statistically significant differences between Group A and Group B with respect to age at surgery, FIGO
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Table 1 Comparison of clinical and economic parameters between implementation group (A) (n = 19) and control group (B) (n = 45) Group A
Group B
Age at surgery (years) Median 67 58 Mean 62 58 Range 36–83 22–85 FIGO stage of disease Stage II 5.3% 2.2% Stage III 73.7% 66.7% Stage IV 21.0% 31.1% Estimated blood loss (cubic centimeters) Median 1400 900 Mean 1536 1205 Range 500–4250 200–5250 Bowel resection in addition to rectosigmoid colectomy Yes 42.1% 42.2% No 57.9% 57.8% Administration of post-operative TPN Yes 26.3% 68.9% No 73.7% 31.1% Tolerance of PO intake (days) Median 3.0 6.0 Mean 4.5 6.1 Range 1–20 1–14 Flatus-post-op (days) Median 6.0 6.0 Mean 6.8 6.9 Range 4–20 2–15 ICU stay (days) Median 2.0 2.0 Mean 2.8 3.2 Range 0–16 0–24 Grade 2–4 post-operative complications Yes 57.9% 62.2% No 42.1% 37.8% Chemotherapy prior to discharge Yes 5.3% 31.1% No 94.7% 68.9% Length of Stay (days) Median 7.0 10.0 Mean 8.7 11.4 Range 3–27 5–30 Readmission within 30 days of discharge Yes 21.1% 33.3% No 78.9% 66.7% Hospital cost (2006 US dollars) Median 19,700 25,110 Mean 23,912 30,205 Range 11,010–84,170 11,980–78,150
Significance (p-value) 0.248⁎
0.615⁎
0.072⁎
0.993⁎ 0.017⁎ 0.013⁎
0.630⁎
0.702⁎
0.746⁎ 0.026⁎ 0.010†
(5.3%) life-threatening post-operative complication in Group A, requiring multiple surgical interventions for abdominal compartment syndrome. There were no anastomotic breakdowns or fistulas associated with this group. The most common complications in Group B were wound infections, adynamic ileus, pelvic abscess, fever, and pelvic hematoma. Two patients (4.4%) in Group B required repeat operative intervention. One patient required re-exploration on post-operative day 13 for a pelvic abscess. The other patient had a superficial abdominal wound separation, requiring secondary closure on post-operative day 11. There was one entero-vaginal fistula, which was managed conservatively and healed spontaneously. One patient in Group B was readmitted on post-operative day 29 secondary to neutropenic fever and sepsis following chemotherapy. The patient subsequently expired on day 17. This was the only postoperative mortality in either group. As shown in Table 1, patients in Group A were statistically significantly less likely to have received post-operative TPN and systemic chemotherapy prior to discharge. Patients in Group A tolerated oral intake a median of 3 days post-operatively, compared to a median of 6 days for patients in Group B, which was a statistically significant difference ( p = 0.013). Similarly, patients in Group A had a median total hospital LOS of 7.0 days, compared to a median LOS of 10.0 days for patients in Group B. This difference was statistically significant on both univariate and multivariate analysis. The median total hospital cost of postoperative care for patients in Group A was $19,700, compared to a median total cost of $25,110 for patients in Group B. Again, this difference was statistically significant on both univariate and multivariate analysis. The cost of intravenous chemotherapy administered prior to discharge was analyzed and demonstrated a median cost of $340 per patient treated. This did not change the statistical significance of the overall hospital costs. Overall, clinical pathway-directed management was associated with a median reduction in total direct and indirect hospital cost of postoperative care of $5410 per patient. Discussion
0.326⁎ 0.043†
FIGO: International Federation of Gynecology and Obstetrics. NGT: nasogastric tube. TPN: total parenteral nutrition. ⁎ univariate analysis. † multivariate analysis.
stage of disease, estimated operative blood loss, the proportion of patients undergoing bowel resection in addition to rectosigmoid colectomy, duration of NGT suction, time to first flatus, duration of ICU stay, incidence of grade 2–4 complications, and 30-day hospital readmission rate. The most common postoperative morbidities in Group A were fever, abscess, adynamic ileus, and Clostridium difficile colitis. There was only one
The American Cancer Society has estimated that 22,430 new cases of ovarian cancer will be diagnosed in the United States in 2007 with 15,280 disease-related deaths [9]. Most patients will present with FIGO Stage III or IV disease. The most powerful predictor of overall survival for these patients is optimal primary cytoreductive surgery followed by platinum and taxane based chemotherapy [10–13]. In order to achieve minimal residual disease, a significant proportion of patients will require extensive resection of pelvic viscera, including resection of the rectosigmoid with primary anastomosis. This procedure has been previously described as having acceptable associated morbidity [14–17]. A challenge that is encountered by the gynecologic oncologist caring for this select group of patients is the appropriate time to reintroduce oral intake. There has not been an established standard of care for early post-operative feeding in the gynecologic oncology population. Randomized controlled trials in gynecologic and gynecologic oncology patients undergoing major surgery have demonstrated that early feeding is
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feasible, well tolerated, and promotes a more rapid recovery compared to those treated conservatively [18,19]. A study by Marx et al. evaluated the effect of fast-track, multimodal rehabilitation in patients with ovarian malignancies and demonstrated an overall benefit with regard to hospital stay as well as medical morbidity [20]. However, there were only ten patients that were evaluated, and different types of colonic resections were performed. To date, there has not been an investigation specifically evaluating the safety and feasibility of rapid diet advancement in patients with advanced ovarian and primary peritoneal cancers undergoing optimal surgery with rectosigmoid resection. The practice of prolonged nasogastric intubation and withholding feeding until bowel function has resumed has been long established in many surgical practices. However, a number of studies have now demonstrated that this practice offers no overall benefit to patient care. Cutillo et al. reported that nasogastric decompression can actually delay the return to normal gastrointestinal function [21]. Post-operatively, gastric emptying function usually returns within 24 h, and colonic activity recovers within 48–72 h of abdominal surgery. Therefore, initiating a diet on post-operative day one or two should be safe and efficacious with regard to overall recovery. Initiating patients who have undergone abdominal or gynecologic procedures on a regular diet as opposed to a clear liquid diet has not been associated with an increase in gastrointestinal complaints [22,23]. Specifically from the colorectal cancer literature, Reismann et al. performed a prospective randomized trial and found that early feeding did not affect the duration of adynamic ileus, which was similar in both study groups [24]. In addition, Behrns et al. demonstrated that patients undergoing various intestinal procedures who were given a clear liquid diet by postoperative day number two were discharged from the hospital sooner than those managed conservatively [25]. The introduction of a clinical, or critical, pathway streamlines the post-operative care of surgical patients and places emphasis on improving cost reduction within a hospital system, presumably without increasing complication rate or readmission rate. One large study conducted by Melbert et al. looked at a specific critical pathway for 385 patients that underwent colorectal resections and concluded that the use of this pathway was statistically significant with regard to shortened lengths of hospital stay, earlier resumption to regular diet, and diminished hospital charges, with no diminution of patients' perceptions of satisfaction with the hospital experience [26]. These outcomes, along with the results of the current case–control study, support the application of a clinical pathway to patients undergoing rectosigmoid colectomy as part of primary cytoreductive surgery for advanced ovarian and peritoneal cancers. Although patients in Group A were older and their surgeries were associated with a higher estimated blood loss, there were no statistically significant differences in the rate of complications or incidence of hospital readmission with 30 days of initial surgery compared to Group B. Notably, patients in Group A tolerated a regular diet a median of 3.0 days earlier than patients in Group B. This finding, coupled with a statistically significant reduction in the proportion of patients receiving chemotherapy during the index admission, yielded a median reduction in the hospital
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LOS of 3.0 days compared to patients in Group B. Overall, management according the prescribed clinical pathway was the only statistically significant and independent predictor of postoperative hospital cost, with a median reduction of $5410 per patient in Group A. Although the administration of chemotherapy did impact on the overall length of stay, omitting the cost of chemotherapy during the primary admission did not demonstrate statistical significance with regard to hospital cost. There are two important limitations of the current study that must be considered in interpreting the results presented. First, the number of subjects in the experimental group (Group A) was relatively modest; however, the study was powered to detect a meaningful difference (20%) in hospital costs associated with management according to the clinical pathway. It is possible that with a larger number of subjects the magnitude of the observed differences in clinical and economic parameters could be less compelling. Second, the case–control study methodology was selected to evaluate the feasibility, safety, and potential economic impact of the prescribed clinical pathway among a homogenous group of patients over a relatively brief period of time. This methodology, however, may not have accounted for all potential factors that may have influenced the observed findings for the clinical and economic outcomes under study. Case–control studies may also be prone to recall bias; however, this risk was minimized by the prospective collection of data for patients in Group A and limiting the outcomes of interest to those parameters that could be objectively determined from the medical record. Despite these limitations, the results of the current study indicate that a critical pathway incorporating rapid diet advancement for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for advanced ovarian and primary peritoneal cancers appears feasible, safe, and is associated with a statistically significant reduction in the length of hospital stay and hospital-related costs. Ideally, this study will provide the basis for a larger, prospective, randomized, multi-institutional collaborative investigation to confirm or refute these initial observations. Acknowledgment This work supported by the Elizabeth Frost Ovarian Cancer Research Fund. References [1] Panella M, Marchisio S, Di Stanislao F. Reducing clinical variations with clinical pathways: do pathways work? Int J Qual Health Care 2003;6: 509–21. [2] Stephen AE, Berger DL. Shortened length of stay and hospital cost reduction with implementation of an accelerated clinical care pathway after elective colon resection. Surgery 2003;133(2):77–82. [3] Pritts TA, Nussbaum MS, Flesch LV, Fegelman EJ, Parikh AA, Fischer JE. Implementation of a clinical pathway decreases length of stay and cost for bowel resection. Ann Surg 1999;230:728–33. [4] Ng WQ, Neill J. Evidence for early oral feeding of patients after elective open colorectal surgery: a literature review. J Clin Nurs 2006;15(6):696–709. [5] Ghosh K, Downs LS, Padilla LA, Murray KP, Twiggs LB, Letourneau CM, et al. The implementation of critical pathways in gynecologic oncology in a managed care setting: a cost analysis. Gynecol Oncol 2001;83(2):378–82.
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