Establishment of genetically diverse patient-derived xenografts of colorectal cancer.

Preclinical compounds tested in animal models often show limited efficacy when transitioned into human clinical trials. As a result, many patients are stratified into treatment regimens that have little impact on their disease. In order to create preclinical models that can more accurately predict tumor responses, we established patient-derived xenograft (PDX) models of colorectal cancer (CRC). Surgically resected tumor specimens from colorectal cancer patients were implanted subcutaneously into athymic nude mice. Following successful establishment, fourteen models underwent further evaluation to determine whether these models exhibit heterogeneity, both at the cellular and genetic level. Histological review revealed properties not found in CRC cell lines, most notably in overall architecture (predominantly columnar epithelium with evidence of gland formation) and the presence of mucin-producing cells. Custom CRC gene panels identified somatic driver mutations in each model, and therapeutic efficacy studies in tumor-bearing mice were designed to determine how models with known mutations respond to PI3K, mTOR, or MAPK inhibitors. Interestingly, MAPK pathway inhibition drove tumor responses across most models tested. Noteworthy, the MAPK inhibitor PD0325901 alone did not significantly mediate tumor response in the context of a KRAS(G12D) model, and improved tumor responses resulted when combined with mTOR inhibition. As a result, these genetically diverse models represent a valuable resource for preclinical efficacy and drug discovery studies.

Minimally invasive colorectal resection for benign pathology is associated with persistent proangiogenic plasma compositional changes.

BACKGROUND: Minimally invasive colorectal resection for cancer is associated with increased plasma levels of numerous proangiogenic proteins for 3 to 4 weeks postoperatively, and plasma from postoperative weeks 2 and 3 stimulates proangiogenic endothelial cell behavior in vitro. It is unknown if similar plasma changes occur after minimally invasive colorectal resection for benign pathology. OBJECTIVE: The aim of this study is to assess 1) plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 after minimally invasive colorectal resection for benign pathology and 2) postoperative plasma's effects on in vitro endothelial cell proliferation (branch point formation), migration, and invasion. DESIGN: Prospectively gathered plasma samples taken from patients undergoing colorectal resection who consented to participate in an institutional review board-approved plasma and data bank were used for ELISAs and in vitro endothelial cell studies. SETTINGS: The plasma and clinical data used were collected at 3 hospitals. PATIENTS: Patients undergoing minimally invasive colorectal resection for benign indications who were enrolled in a plasma/data bank and for whom adequate samples and volumes of plasma were available were included in the study. MAIN OUTCOME MEASURES: Perioperative plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 were the primary outcomes measured. In vitro rates of endothelial cell branch point formation, migration, and invasion were determined after the addition of preoperative and postoperative plasma samples to endothelial cell cultures. RESULTS: Plasma from 86 patients undergoing minimally invasive colorectal resection for benign indications was assessed (diverticulitis, 30; benign polyps, 56). Plasma levels of angiopoetin-2, placental growth factor, and soluble vascular cell adhesion molecule-1 were significantly increased for 3 to 4 weeks postoperatively compared with preoperative levels. In regard to the endothelial cell culture assays, significantly increased endothelial cell branch point formation, invasion, and migration results were noted with plasma from the second and third weeks postoperatively in comparison with preoperative culture results. LIMITATIONS: The weaknesses of this study are the limited numbers of late postoperative plasma samples and the need to bundle late samples into 7- to 12-day time blocks. CONCLUSIONS: Minimally invasive colorectal resection for benign pathology is associated with persistent proangiogenic plasma alterations similar to those found in patients who have cancer. Surgical trauma and not the indication is the likely cause.

Bioabsorbable staple line reinforcement in restorative proctectomy and anterior resection: a randomized study.

BACKGROUND: Anastomotic complications, including leaks, strictures/stenoses, and bleeding, cause considerable mortality and morbidity after colorectal surgery. OBJECTIVE: The aim of this study was to assess whether the use of a synthetic, bioabsorbable staple line reinforcement material with circular staplers would reduce postoperative anastomotic leakage in patients with a colorectal, coloanal, or ileoanal anastomosis. DESIGN: This was a randomized study that compared outcomes in patients in whom the reinforcement material was used with those in patients who were not given the material. SETTINGS: This study was conducted at several centers in the United States. PATIENTS: The 258 patients (123 in the reinforcement group and 135 control subjects) underwent surgery for a variety of conditions, but most (n = 200) were treated for rectal cancer. MAIN OUTCOME MEASURES: The main outcome measures were occurrence of anastomotic leaks and other complications according to the study protocol. RESULTS: There were no significant differences in the 2 study groups with respect to age, BMI, ASA physical status, operating time, diagnosis, previous chemoradiotherapy, surgical technique, or 30-day complications, except for a higher rate of small-bowel obstruction (p = 0.03) and anastomotic stricture (p = 0.006) in the control group. The overall anastomotic leak rate was 12% (bioabsorbable staple line reinforcement, 11.4%; no bioabsorbable staple line reinforcement, 12.6%). LIMITATIONS: The study was nonblinded and was terminated at the first planned interim analysis because of insufficient power to detect an intergroup difference in anastomotic leak rate in the time allotted for the investigation. CONCLUSIONS: Reinforcing the circular staple line in colorectal anastomoses with bioabsorbable material did not significantly affect the anastomotic leak rate but may have reduced anastomotic strictures. Most strictures did not require an anastomotic revision or delay in stoma closure. The bioabsorbable material may positively affect some aspects of the healing of circular stapled colorectal anastomoses; however, additional research on factors associated with anastomotic leakage is needed.

Anastomotic leaks: technique and timing of detection.

BACKGROUND: Despite the proven benefits of laparoscopic colorectal surgery, the rate of anastomotic leaks has not changed. This study looks at the time of presentation of anastomotic leaks between laparoscopic and open colectomies. METHODS: Retrospective chart review was performed between July 2008 and 2012. Two groups were created, laparoscopic and open. The time of presentation of significant leaks requiring reoperation were compared between the groups by index colectomies. Statistical analysis is presented as paired t test and chi-square test (P < .05). RESULTS: From 1,424 segmental colectomies, the anastomotic leak rate between the two groups was not statically significant (P = .69). No difference in the time of leak detection was evident (P = .67). Mortality rate was equal between the groups. The overall complication rate of the entire cohort was statically significant (P ≤ .001). CONCLUSION: The timing of anastomotic leak detection does not differ between laparoscopy and open colorectal resections.

Outcomes of ileocolic resection and right hemicolectomies for Crohn's patients in comparison with non-Crohn's patients and the impact of perioperative immunosuppressive therapy with biologics and steroids on inpatient complications.

BACKGROUND: The purpose of this study was to compare medication use and complication rates between Crohn's disease (CD) and non-CD patients undergoing ileocolic resections and right hemicolectomies. METHODS: A review of patients who underwent ileocolic resections and right hemicolectomies from January 1, 2003, through December 31, 2010, was performed. Data collected included demographics and clinical information, biologics use (eg, infliximab, adalimumab), other medication use (eg, steroids), complications, and mortality. RESULTS: There were 791 records reviewed, with 93 CD patients. There was no significant difference in major or minor complications, anastomotic leaks, operating room time, or postoperative ileus occurrence between the CD and non-CD groups (P > .05). Use of biologics and steroids were significantly higher among the CD patients. Mortality, age, and American Society of Anesthesiologists score were significantly higher in the non-CD group. CONCLUSIONS: Ileocolic resections and right hemicolectomies in CD patients are not associated with an increase in complication rates even when the patients use steroids and biologics in the preoperative period.

Plasma from the second and third weeks after open colorectal resection for cancer stimulates in vitro endothelial cell growth, migration, and invasion.

INTRODUCTION: Angiogenesis is central to wound healing and tumor growth. Postoperative (postop) plasma from weeks 2 and 3 after minimally invasive colorectal resection (MICR) stimulates endothelial cell (EC) migration (MIG), invasion (INV), and proliferation (all vital to angiogenesis) compared with preoperative (preop) plasma results and may promote postop tumor growth. The purpose of this study was to determine whether plasma from open colorectal resection (OCR) patients has similar proangiogenic EC effects in vitro. METHODS: OCR cancer patient plasma from institutional review board-approved banks was used; patients with preop and one postop sample from postoperative days (POD) 7-33 were eligible. Samples were bundled into 7- to 13-day periods and considered as single time points. In vitro cultures of human umbilical venous ECs were used for the EC proliferation (BPF, Branch Point Formation), INV, and MIG assays performed with preop, POD 7-13, POD 14-20, and POD 21-33 plasma. Data were analyzed by paired t test and were reported as mean ± standard deviation (significance, P < 0.05). RESULTS: Plasma from 53 cancer patients (25 rectal and 28 colon) was used. Because of limited postop samples, the number for each time point varies: POD 7-13, n = 30; POD 14-20, n = 26; and POD 21-33, n = 17. In vitro EC BPF was significantly greater at the POD 7-13 (P < 0.0001) and POD 14-20 (P < 0.0001) time points versus preop results. Significantly greater EC INV and MIG were noted on POD 7-13 and POD 14-20 versus the preop plasma results (P < 0.0001). In regards to POD 21-33, a significantly greater result was noted only for the INV assay versus preop. CONCLUSIONS: Plasma from weeks 2 and 3 after OCR stimulates in vitro EC BPF, INV, and MIG. A significant difference from preop baseline was noted only for the INV assay in week 4. The OCR and previous MICR results were largely similar. Tumor angiogenesis may be stimulated after OCR and MICR for 3 weeks. Further studies are warranted.

Citrulline: a potential immunomodulator in sepsis.

BACKGROUND: Sepsis leads to a complex systemic response of cytokines (both pro- and anti-inflammatory) and more recently recognized adipokine mediators. Endothelial nitric oxide (NO) may be a key component in regulating this response, but the pharmacologic manipulation of endothelial NO via L-arginine supplementation or inhibitors has provided inconsistent clinical data related to outcomes. These failures are related to the metabolism of L-arginine in the liver, toxicity of L-arginine, and asymmetric dimethylarginine inhibition, all of which may explain the "arginine paradox." L-citrulline (CIT) offers a potentially valuable means of supplementing arginine and therefore impacting favorably NO availability. The goal of this study was to determine whether CIT supplementation altered the systemic response of mediators and cytokines in a rat model of sepsis with varying degrees of severity. METHODS: Sepsis was induced with 2 models of cecal ligation and puncture (CLP) of varying severity in Wistar rats. CIT supplementation was provided to half the animals as 8% CIT-supplemented feed for 3 weeks. Baseline mediator levels were assessed in the Wistar rats followed by comparison of the following groups at days 0, 1, and 3: sham-operated; CLP 8-mm (localized); and CLP 12-mm (extensive). The following analyses were performed in the groups: interleukin-6 (IL-6), IL-8, IL-10, resistin, and adiponectin levels (enzyme-linked immunosorbent assay performed in duplicate). L-arginine and CIT were measured with high-performance liquid chromatography combined with mass spectrometry. RESULTS: Ninety-eight Wistar rats were evaluated, and survival was similar in both sepsis models with and without CIT. Serum IL-6 levels were lower in the CIT/CLP 8-mm group compared to the standard rat chow (STD)/CLP 8-mm group (41 vs 117 pg/mL; P = .011) on postoperative day 3. Serum IL-8 and IL-10 responses were similar across all groups. Serum resistin levels were lower in the CIT/CLP 12-mm group compared to the STD/CLP 12-mm group in the more severe sepsis model on day 3 (19 vs 38 ng/mL; P < .0001). The levels of serum L-arginine were greater in the CIT-supplemented animals compared to STD rodent diet animals before surgical insult (86.3 vs 294.0 µM; P = .004). Adiponectin was not affected by CIT supplementation. CONCLUSION: CIT may decrease the proinflammatory mediator response (IL-6 and resistin) without impairing the secretion of anti-inflammatory mediators (IL-10 and adiponectin) and thereby provide a safe means of immunomodulation that preserves the anti-inflammatory mediator response.

Serum adiponectin, resistin, and circulating soluble receptor for advanced glycation end products in colectomy patients.

AIM: Surgical trauma and associated complications are frequently related to physiological stress during colectomy. This study evaluated the response of adiponectin, resistin, and circulating soluble receptor for advanced glycation end products (sRAGE) in colectomy patients with or without an enhanced recovery protocol. METHOD: Serum samples were collected from 44 colectomy patients at 3 timframes. The surgical procedures were laparoscopic (LAP), hand-assisted laparoscopic (HALS), or open colectomy (OPEN). Adiponectin, resistin, and sRAGE levels were determined by ELISA. Repeated measures ANOVA was applied and P values < 0.05 were considered significant. RESULTS: A total of 132 (44 × 3) sera were used for analysis. Levels of adiponectin was significantly decreased between PREOP and POD3 (P < 0.001). Conversely, concentrations of resistin significantly increased from PREOP to POD1 and returned to baseline value by POD3 (P < 0.001). Serum sRAGE levels were significantly higher in LAP in comparison with HALS (P = 0.004) and OPEN (P < 0.001). sRAGE levels were significantly higher in sera of patients that underwent ERP (P < 0.001). CONCLUSIONS: Serum adiponectin, resistin, and sRAGE have the potential to develop into a panel of stress markers. Higher sRAGE levels in sera of LAP and ERP patients may be indicative of a protective and syngeristic role for colectomy recovery.

Minimally invasive colorectal resection is associated with a rapid and sustained decrease in plasma levels of epidermal growth factor (EGF) in the colon cancer setting.

BACKGROUND: Epidermal growth factor (EGF) stimulates tumor growth directly via tumor cell EGF receptors or indirectly via its proangiogenic effects. This study's purpose was to determine the impact of minimally invasive colorectal resection (MICR) on postoperative (postop) plasma EGF levels in the colorectal cancer (CRC) and benign disease settings and to see if preoperative (PreOp) EGF levels are altered in cancer patients. METHODS: MICR patients with benign pathology (n = 40) and CRC (n = 48) had blood samples taken PreOp and on postoperative days (POD) 1 and 3. In some patients, late samples were taken between POD7 and POD60; these were bundled into 7-day blocks and considered as single time points. EGF levels were determined by enzyme-linked immunosorbent assay (ELISA) and results were reported as mean ± SD after logarithmic transformation. The Student t test was used (p < 0.008 after Bonferroni correction). RESULTS: The cancer and benign groups were comparable except for age. The mean PreOp CRC plasma EGF level (122.9 ± 75.9 pg/ml) was significantly higher than that of the benign group (85.3 ± 38.5 pg/ml) (p = 0.015). The cancer group's EGF levels were significantly decreased on POD1 and POD3 and for the POD31-55 time point (mean EGF level = 63.1 ± 42.2 (n = 10). The benign group's POD3 and POD7-14 EGF levels were significantly lower than the PreOp level; later levels returned toward baseline. Small late sample size limited analysis. CONCLUSION: Plasma EGF levels are significantly higher in cancer patients. MICR is associated with a significant decrease in EGF levels early postop in both cancer and benign settings. Unlike the benign group, EGF blood levels in cancer patients remain low during the second postop month. A larger study with more late samples is needed to verify these results. EGF may have value as a tumor marker.

Colorectal resection is associated with persistent proangiogenic plasma protein changes: postoperative plasma stimulates in vitro endothelial cell growth, migration, and invasion.

INTRODUCTION: Plasma vascular endothelial growth factor (VEGF) levels are elevated for weeks after minimally invasive colorectal resection (MICR). Decreased plasma angiopoietin-(Ang) 1 and increased Ang-2 levels have been noted on postoperative days (POD) 1 and 3. These proangiogenic changes may stimulate tumor growth postoperatively (postop). This study's purpose was to track plasma VEGF, Ang-1, and Ang-2 levels for 4 to 8 weeks after MICR for cancer and to assess the impact of preoperative (preop) and postop plasma on in vitro endothelial cell (EC) behavior. METHODS: Blood samples from 105 MICR patients were taken preop, on POD 5 and at varying time points for 2 months. Samples from 7 day time blocks after POD 5 were bundled to permit statistical analysis. Plasma protein levels were measured via enzyme-linked immunosorbent assay. In vitro EC branch point formation, EC invasion, and EC migration assays were carried out with preop, POD 7 to 13 and 14 to 20 plasma. The t test and Bonferonni correction was used. RESULTS: VEGF levels were significantly elevated on POD 5 and 7 to 13; lesser increases were noted on POD 14 to 20 and 21 to 27. Ang-2 levels were significantly increased at all time points postop. No significant Ang-1 changes were noted. When compared to preop EC culture results, there was significantly more EC branch point formation, EC invasion, and EC migration assays noted with POD 7 to 13 and POD 14 to 20 plasma. CONCLUSIONS: MICR is associated with proangiogenic plasma changes for 2 to 4 weeks and plasma from POD 7 to 13 and 14 to 20 stimulated EC growth, invasion, and migration. Postop plasma may stimulate the growth of residual tumor.

Preoperative considerations and creation of normal ostomies.

Stomas provide fecal diversion in emergent and elective settings. Preoperative planning and counseling are extremely important to the creation of an acceptable and functional ostomy for the surgeon and patient. Proper site selection will help decrease the incidence of postoperative complications. Ileostomy, colostomy, and cecostomy indications and techniques are discussed.

Laparoscopic vs. hand-assisted laparoscopic sigmoidectomy for diverticulitis.

INTRODUCTION: Sigmoid colectomy for diverticulitis can be technically challenging because of severe inflammation in the left-lower quadrant and pelvis. We hypothesized that hand-assisted laparoscopic technique may facilitate laparoscopic completion of this surgery while retaining the short-term benefits associated with "pure" laparoscopic surgery, in which an incision is made only for extracting the specimen. This study was designed to compare the outcomes of patients who underwent totally laparoscopic or hand-assisted laparoscopic sigmoidectomy for diverticulitis. METHODS: We reviewed our prospectively collected patient database from July 2001 to June 2004 and compared the intraoperative data and postoperative outcomes of patients who underwent elective laparoscopic or hand-assisted laparoscopic sigmoidectomies for diverticulitis. Complicated patients (with abscess or fistulas) also were separately analyzed. RESULTS: The hand-assisted laparoscopic (mode age, 57 years; 48 percent male) and laparoscopic sigmoidectomy (mode age, 56 years; 90 percent male) groups were similar with regard to age and gender. Overall, patients who underwent laparoscopic (n = 21) vs. hand-assisted laparoscopic (n = 21) sigmoidectomies had a significantly longer operative time (197 +/- 42 vs. 171 +/- 34 minutes, P = 0.04) and shorter incision length (5 +/- 2.1 vs. 9.3 +/- 4.1 cm, P = 0.0001). Patients with complicated diverticulitis (n = 14; abscess, colovesical fistula, enterocolic fistula) who underwent laparoscopic sigmoidectomies (n=4) had a significantly longer operative time compared with hand-assisted laparoscopic sigmoidectomy (n = 10) group (255 +/- 18 vs. 177 +/- 34 minutes, P = 0.001). Conversion rate for the laparoscopic group was significantly higher (3/4 vs. 1/10, P = 0.04, Fisher exact) when complicated diverticulitis was present. There were no differences in postoperative outcomes or incision lengths in the complicated group. CONCLUSIONS: Outcomes after hand-assisted laparoscopic sigmoidectomy for diverticulitis are similar to those seen in the pure laparoscopic method, with lower conversion rates and shorter operative times. Hand-assisted laparoscopic sigmoid resection for diverticulitis is an attractive alternative to a "pure" laparoscopic method in complicated cases.

Effects of a laparoscopic course on student interest in surgical residency.

BACKGROUND: The number of surgical residency applicants has been declining. Early introduction of the discipline of surgery is thought to stimulate early interest in surgical residency. This study investigated the hypothesis that a laparoscopic skills course introduced in preclinical years would stimulate student interest in entering surgical residency. METHODS: Preclinical medical students participated in a laparoscopic skills training course. All students underwent an animate laboratory at the beginning and at the end of the course. Students were divided into 4 separate groups: virtual reality, box trainer, both trainers, and control group. Before and after the course, students were asked their residency interest. First- and second-year medical students participated in the course. RESULTS: Before the course, 56% of the students desired to go into general surgery or a surgical subspecialty. After the course, 49% of the students expressed interest in entering general surgery or a surgical subspecialty. A decrease occurred in students who desired to go into surgical subspecialty residency from 31% to 15% (P = NS), and an increase occurred in students who desired to go into general surgery residency from 25% to 34% (P = NS). No statistically significant difference was seen in the 4 individual training subgroup analyses. CONCLUSIONS: Participation in a laparoscopic skills course does not affect medical student interest in entering surgical residency. A trend was noted in students choosing general surgery over surgical subspecialty training after this course. Surgical educators need to investigate methods to encourage preclinical medical student interest in surgical residencies.

Anorectal anatomy and embryology.

The anal canal is complex in its anatomy and its embryologic origin. The intricate and changing histology of the anal canal explains the different types of anal cancer. In addition, an understanding of the venous and the lymphatic drainage of the anal canal helps to explain its methods of dissemination. Finally, the basis for the treatment of anal cancer is derived from the cancer's anatomic origins.

IFN-gamma production is specifically regulated by IL-10 in mice made tolerant with anti-CD40 ligand antibody and intact active bone.

We have developed a strategy to induce tolerance to allografts, involving cotransplantation of allogeneic intact active bone and transient anti-CD40 ligand mAb therapy. Tolerance induced by this approach in C57BL/6 mice receiving BALB/c hearts is not mediated by deletional mechanisms, but by peripheral regulatory mechanisms. Tolerance is associated with diminished ex vivo IFN-gamma production that is donor specific, and a reduction in the frequency of IFN-gamma-producing cells. Splenocytes from mice tolerant to BALB/c grafts, but sensitized to third-party C3H skin grafts, demonstrated normally primed ex vivo IFN-gamma responses to C3H stimulators. Neutralizing anti-IL-10 and anti-IL-10R, but not anti-TGF-beta, anti-IL-4, or anti-CTLA-4, Abs restored the ex vivo IFN-gamma response to BALB/c stimulators. There was no significant difference in IL-2 or IL-4 production between tolerant and rejecting mice, and anti-IL-10 mAbs had no effect on IL-2 or IL-4 production. The Cincinnati cytokine capture assay was used to test whether suppression of IFN-gamma production in vivo was also a marker of tolerance. In naive mice, we observed a dramatic increase in serum IFN-gamma levels following challenge with allogeneic BALB/c splenocytes or hearts. Tolerant mice challenged with allogeneic BALB/c splenocytes or hearts made significantly less or undetectable amounts of IFN-gamma. No IL-4 or IL-10 production was detected in tolerant or rejecting mice. Collectively, our studies suggest that active suppression of IFN-gamma production by IL-10 is correlated with, and may contribute to, tolerance induced with intact active bone and anti-CD40 ligand mAbs.

Acute xenograft rejection mediated by antibodies produced independently of TH1/TH2 cytokine profiles.

There is substantial support for the hypothesis that T(H)1 cytokine responses are critical for the normal elaboration of allograft rejection. Recent studies by Wang et al. (1) underscore the importance of T(H)2 responses in xenograft rejection and revealed that T(H)1 cytokines, IL-12 and interferon-gamma (IFN-gamma), can negatively regulate the development of humoral responses necessary for xenograft rejection. Their exceptional studies prompted us to test whether the ability of allografts to elicit cellular rejection and xenografts to induce humoral rejection also result from the differential ability to induce T(H)1 and T(H)2 responses. We compared the kinetics of antibody and cytokine (IFN-gamma and IL-4) production in C57BL/6 mice following allograft transplantation with BALB/c hearts and in C57BL/6 and BALB/c mice following transplantation with Lewis rat hearts. We also compared the ability of BALB/c mice, deficient in the ability to produce IL-4 or IFN-gamma, to reject xenografts and produce xenoantibodies. We observed that T(H)1/T(H)2 cytokine production minimally affected the kinetics of graft rejection but regulated the magnitude of IgG subclass production. Anti-graft IgM played a critical role in initiating acute antibody-mediated xenograft rejection, and the production antigraft IgM was unaffected by IL-4 or IFN-gamma deficiency. In contrast to the report by Wang et al. (1), we conclude that antibody-mediated xenograft rejection in the concordant Lewis rat heart-to-C57BL/6 mouse xenotransplantation model is dependent on anti-IgM production but independent of T(H) cytokine profiles.

A pilot study comparing percutaneous decompression with decompressive laparotomy for acute abdominal compartment syndrome in thermal injury.

Abdominal Compartment Syndrome (ACS) has multiple causes, and decompressive laparotomy has been the most frequent modality to prevent worsening cardiovascular, respiratory, and renal function. This pilot study evaluated the utility of percutaneous drainage (PD) of peritoneal fluid compared with decompressive laparotomy in burn patients. A 26-month review was conducted. Nine of 13 (69%) study patients developed intra-abdominal hypertension (IAH) that progressed to abdominal compartment syndrome in 4 (31%). All were treated with PD using a diagnostic peritoneal lavage catheter. Peritoneal fluid analysis revealed a sterile plasma ultrafiltrate with electrolyte and other chemistries reflecting patient serum levels. Five patients underwent PD successfully, and their IAH did not progress to ACS. Four patients with greater than 80% TBSA and severe inhalation injury did not respond to PD and required decompressive laparotomy. There was no evidence of bowel edema, ischemia, or necrosis. All patients requiring decompressive laparotomies died either from sepsis or respiratory failure. Percutaneous decompression is a safe and effective method of decreasing IAH and preventing ACS in patients with less than 80% TBSA thermal injury.