INTRODUCTION

The use of negative-pressure wound therapy for open abdomen (NPWTOA) enables the temporary closure of the abdominal cavity. The indications of NPWTOA are well defined for abdominal trauma: it reduces the risk of abdominal compartment syndrome in the case of “damage control” or “packing” surgery and aggressive resuscitation.1-3 Other indications for NPWTOA may include complications after surgery including oncologic resection, and especially during the management of peritonitis, severe pancreatitis, or vascular complications.1

With NPWTOA, the abdominal cavity is covered with foam and a drape to help isolate and protect the abdominal viscera. A negative pressure is delivered through the foam to remove peritoneal fluid, reduce edema, and minimize fascial retraction and loss of tissue. Thus, NPWTOA reduces the risk of intra-abdominal hypertension and permits a delayed wall closure after an additional surgical exploration associated with intestinal resection or delayed intestinal anastomosis.

Use of NPWTOA induces two actions. First, a macro-deformation induces wound shrinkage caused by the collapse of the foam onto the wound surface. This brings the wound edges together and eliminates exudate and infectious elements. Second, a microscopic deformation reduces edema, increases perfusion and cell proliferation and migration, promotes angiogenesis, and produces granulation tissue.4-8 Because of this microscopic deformation, the use of NPWTOA in cases of malignant wounds is controversial. Some authors claim that NPWTOA may increase the risk of tumor proliferation or dissemination.4,6,7 However, for patients presenting a life-threatening postoperative complication such as peritonitis, NPWTOA could be considered in a risk/benefit analysis, especially after potentially curative oncologic surgery.

In this study, the researchers evaluated the effect of NPWTOA on overall survival (OS) and disease-free survival (DFS) in patients who underwent surgical reintervention for life-threatening postoperative complications after curative surgery for peritoneal malignancy (PM).

METHODS Patient Population

The authors searched their institution’s prospectively managed PM database to identify patients who underwent surgical reintervention after cytoreductive surgery for PM between January 2011 and January 2017. All patients who underwent NPWTOA during a surgical reintervention after cytoreductive surgery for PM were considered. This study was performed in accordance with the precepts established by the Helsinki Declaration. The authors used a prospectively collected database, and all patients signed an informed consent to share their anonymous data.

For all patients considered, the following data were extracted from the prospectively collected database of peritoneal carcinomatosis: sex, age at time of surgery, weight, height, American Society of Anesthesiologists score, origin of PM, history of neoadjuvant chemotherapy, value of carcinoembryonic antigen and CA-19-9 markers at time of cytoreductive surgery, extent of PM (determined according to the Peritoneal Cancer Index),9 realization of hyperthermic intraperitoneal chemotherapy (HIPEC), duration of surgery without HIPEC, chemotherapy agent used for the HIPEC, and completeness of cytoreduction score (CC score).9,10

Postoperative complications were evaluated by a research nurse within 90 days after surgery and classified as medical or surgical.11 The National Cancer Institute’s Common Terminology Criteria for Adverse Events version 4.0 was used to grade complications.11,12 Grades 3 (severe adverse event), 4 (life-threatening consequences), and 5 (death) were recorded.

Surgical Management

Cytoreductive surgery was performed by a member of the surgical team, combining organ resection and peritonectomy procedures10 with the goal of achieving complete macroscopic resection (CC0 or CC1) for potentially curative resection. Following macroscopically complete cytoreductive surgery, HIPEC was considered based on the primary disease site and on clinical trials ongoing in the department. A closed HIPEC technique was used. The cytotoxic agents used were cisplatin, mitomycin C, oxaliplatin, and irinotecan, alone or in combination. The duration of HIPEC similarly depended on the site of the primary disease.13,14

For patients who presented a life-threatening postoperative complication requiring surgical reintervention, NPWTOA was considered in the case of hemorrhage requiring massive transfusion or questionable bowel vitality requiring a “second look” procedure. The decision to use NPWTOA was based on a surgical, anesthetic, and ICU team determination. The system used was ABThera (KCI/3 M).15 After NPWTOA, a second-look laparotomy was performed 48 to 72 hours after the first laparotomy, and the abdomen was closed when feasible.

Statistical Analysis

Descriptive results were expressed numerically (percentage) for qualitative variables and by median (minimum-maximum) for quantitative variables. The researchers compared the experimental population who underwent NPWTOA to a paired population of patients who underwent surgical reintervention for any life-threatening complication. A 1:3 pairing was made according to the Peritoneal Cancer Index by allowing a difference of ±5 to the maximum, strictly on complete cytoreduction, PM origin, and the presence of survival data. Data were compared with conditional logistic regression. The researchers calculated OS and DFS from the date of HIPEC to the last known date of follow-up. They estimated the OS curve and DFS curve using the Kaplan-Meier method and performed survival time comparisons between groups using the log-rank test. P < .05 was considered statistically significant. The statistical analyses were performed with SAS 9.4 (SAS Institute Inc).

RESULTS

Among 719 cytoreductive surgeries for PM, 13 patients underwent NPWTOA during surgical reintervention after oncologic surgery for PM. Among them, the origin of the PM was the colon (5/13), gastric (4/13), ovarian (2/13), or pseudomyxoma peritonei (2/13). The indications for reintervention varied: two patients presented with mesenteric ischemia, three had an anastomotic fistula, two had an iatrogenic small bowel fistula, three presented with a life-threatening hemodynamic instability, and three had a vascular lesion with massive transfusion. Clinicopathologic data are presented in Table 1.

Table 1 - CLINICOPATHOLOGIC AND PREOPERATIVE DATA FOR PATIENTS WITH AND WITHOUT NPWTOA Variable Overall (N = 36), n (%) NPWTOA (n = 9), n (%) No NPWTOA (n = 27), n (%) P Baseline characteristics Sex  Female 18 (51.4) 3 (37.5) 15 (55.6)  Male 17 (48.6) 5 (62.5) 12 (44.4) Age at time of surgery, y,
median (min-max) 61.15 (36.8–71.39) 65.32 (38.78–69.01) 60.83 (36.8–71.39) .807 ASA score  1 4 (13.8) 1 (16.7) 3 (13)  2 23 (79.3) 5 (83.3) 18 (78.3)  3 2 (6.9) 2 (8.7) Oncologic characteristics CEA, median (min-max) 3 .1 (0.6–50.0) 1.7 (0.8–6.0) 3.9 (0.6–50.0) .272 CA-19-9, median (min-max) 23 (6–214) 24 (13–145) 19 (6–214) .363 PCI, median (min-max) 14.5 (0–32) 15 (0–31) 14 (1–32) 1.0 Completeness of cytoreduction  0 mm (CC0) 28 (77.8) 7 (77.8) 21 (77.8) 1.0  <2 mm (CC1) 8 (22.2) 2 (22.2) 6 (22.2) HIPEC performed 34 (94.6) 7 (77.8) 27 (100) .996

Abbreviations: ASA, American Society of Anesthesiologists; CC, completeness of cytoreduction score; CEA, carcinoembryonic antigen; HIPEC, hyperthermic intraperitoneal chemotherapy; NPWTOA, negative-pressure wound therapy for open abdomen, PCI, Peritoneal Cancer Index.

Missing data: sex: n = 1; age: n = 16; CEA: n = 12; CA-19-9: n = 14; ASA score: n = 7.

Nine patients were matched to three controls each (n = 27). Four patients were excluded because they could not be matched to any patient according to the matching criteria: Two did not present peritoneal metastasis initially and underwent a prophylactic HIPEC according to phase 3 study; one underwent debulking surgery with a CC score of 3 without HIPEC, and one had 1 day of “open abdomen” because he was hemodynamically unstable, thus transferred to intensive care, and had HIPEC and parietal closure the next day.

There was no difference between the NPWTOA group and the matched cohort regarding clinicopathologic criteria. Table 2 reports postoperative complications.

Table 2 - POSTOPERATIVE MORBIDITY AND COMPLICATIONS IN PATIENTS WITH AND WITHOUT NPWTOA Complication Type Overall, N = 36, n (%) NPWTOA, n = 9, n (%) No NPWTOA n = 27 (%) P Major complications 34 (97.1) 7 (87.5) 27 (100) .995 Hematologic 17 (50) 3 (42.9) 14 (51.9) .842 Cardiovascular 14 (41.2) 6 (85.7) 8 (29.6) .998 Surgical 30 (88.2) 5 (71.4) 25 (92.6) .240 Gastrointestinal 21 (61.8) 7 (100) 14 (51.9) .996 Respiratory 21 (61.8) 5 (71.4) 16 (59.3) .671 Nephrologic 9 (26.5) 2 (28.6) 7 (25.9) .740 Urologic 5 (14.7) 1 (14.3) 4 (14.8) .740

Abbreviation: NPWTOA, negative-pressure wound therapy for open abdomen.

Missing data: major complication: n = 1; all other categories: n = 2.

After a median follow-up of 47 months, across the entire paired population (N = 36), 21 patients presented a recurrence: 11 were uniquely peritoneal, 4 were uniquely extraperitoneal, and 6 were in both sites. A uniquely peritoneal recurrence occurred in 3 (60%) and 8 (50%) patients in the NPWTOA and non-NPWTOA groups, respectively.

Among the patients who underwent NPWTOA, the median OS and DFS were 4.8 and 4.0 months, respectively. Among the non-NPWTOA group, the median OS and DFS were 35 and 13.9 months, respectively. There was no significant difference between the NPWTOA and non-NPWTOA groups regarding OS (Figure 1; P = .391), but there was a significant between-group difference for DFS (Figure 2; P = .022).

Figure 1:

KAPLAN-MEIER ESTIMATES OVERALL SURVIVAL AFTER SURGICAL RE-INTERVENTION AFTER CRS/HIPEC WITH VERSUS WITHOUT NPWTOAAbbreviations: CRS, cytoreductive surgery; HIPEC, hyperthermic intraperitoneal chemotherapy; NPWTOA, negative-pressure wound therapy for open abdomen.

Figure 2:

KAPLAN-MEIER ESTIMATES DISEASE-FREE SURVIVAL AFTER SURGICAL REINTERVENTION AFTER CRS/HIPEC WITH VERSUS WITHOUT NPWTOAAbbreviations: CRS, cytoreductive surgery; HIPEC, hyperthermic intraperitoneal chemotherapy; NPWTOA, negative-pressure wound therapy for open abdomen.

DISCUSSION

The present study suggests, despite a limited population, that NPWTOA negatively impacts the long-term prognosis of patients with life-threatening postoperative complications following cytoreductive surgery for PM, probably by increasing tumor growth. Thus, providers should avoid NPWTOA in these patients. To the authors’ knowledge, this study is the first to evaluate the use of NPWTOA in patients with PM. The length of DFS was significantly shorter in the NPWTOA group compared with the control group, and there was a similar trend in median OS (4.8 vs 35 months; P = .391).

Given the complexity of the mechanical environment generated at the wound, the pathophysiology of increased cancer proliferation is not well defined.4 The cell strain deformation induced by NPWT results in an alteration of cell proliferation, migration, and differentiation by altering the cell matrix and influencing growth factor4,8,15 and could increase cancer proliferation. Angiogenesis at the wound site may also be involved; it is initiated by microdeformation and increased by vascular endothelial growth factor.4-6 Although the risk of proliferation or tumor migration is not formally determined, 3M (a supplier of vacuum-assisted closure devices)7 and the Haute Autorité de Santé16 already contraindicate the use of NPWT on neoplastic wounds, where it is reserved for palliative support.17,18

The placement of NPWTOA is beneficial in some indications;1 however, no definitive data exist regarding the management of severe peritonitis with the open abdomen.1,19,20 Given the findings of the present research, it seems necessary to find an alternative for patients with PM. Interesting alternative abdominal closure techniques exist without negative-pressure systems, such as the “Bogota bag,” the exclusive skin closure over a resorbable mesh (Vicryl) or a Velcro-type sheath as advocated by Wittmann et al.21 In 2013, Kaushik et al22 reported their experience performing an open abdomen procedure on 14 patients with gynecologic cancers without PM. No NPWTOA was performed. The closure method was variable, but the sterile saline bag (Bogota bag) was the most commonly used.

Among several surgeons in the authors’ team, decision-making criteria for NPWTOA were nonstandardized for surgery in patients in hemorrhagic or septic shock, but NPWTOA was the preferred approach in life-threatening postoperative complications when doubts regarding control of peritoneal sepsis or digestive ischemia occurred. Based on the retrospective aspect of matching and analysis, NPWTOA could have prevented more serious complications than non-NPWTOA. Further, intraoperative hemorrhage or repeated transfusions, especially during gastric cancer surgery,23 increase the risk of peritoneal recurrence.23-25 However, the matching limited this bias.

The indications of NPWTOA are uncommon, and its evaluation in larger or randomized studies would be difficult because of the infrequency of the procedure. Between January 2011 and January 2017, 105 NPWTOA procedures were performed in the authors’ institution for emergency or trauma surgery, and only 13 NPWTOA procedures (12.4%) were performed during surgical reintervention following cytoreductive surgery for PM. Despite this small patient population, exacerbated by the inability to match all patients treated with NPWTOA, the present study provides strong evidence for avoiding this technique because of its prognostic influence.

CONCLUSIONS

This study highlights the increased risk of disease progression after the use of NPWTOA post curative surgery of a PM. Although the limited sample size precludes definite conclusions, these results support the contraindication of using NPWTOA following curative treatment of PM.

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