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AIM The aim of this study is to report changes in health-related quality of life attributable to lateral internal sphincterotomy for treatment of anal fissure. There is very little evidence on whether the overall health-related quality of life of patients is detrimentally affected by the condition, or which aspects of self-perceived health status improve after lateral internal sphincterotomy. This study will articulate which aspects of health tend to improve and guide postoperative expectations appropriately. Knowledge gained from this study may also identify gaps in an individual patient's episode of care. METHOD Patients were prospectively identified when they consented to surgical treatment of their anal fissure and were contacted by phone to participate. Participants completed a number of patient-reported outcomes preoperatively and 6 months postoperatively. Faecal incontinence-related quality of life, pain and depression were measured at both time points. The severity of faecal incontinence was measured at both times. RESULTS Participants reported high levels of pain preoperatively. Postoperatively, improvement in pain exceeded the threshold of clinical relevance (P

To determine the impact of surgical technique on the incidence of perineal hernia after abdominoperineal resection (APR). A retrospective analysis was performed on patients who underwent APR between May 2007 and March 2018 at our institution using our prospectively maintained Colorectal Cancer Database. Demographic and clinical parameters were compared between the open APR (OAPR) and laparoscopic APR (LAPR) groups using Student’s t test, chi-squared, or Fisher’s exact test. Putative risk factors were then analyzed using a Cox proportional hazard model with perineal hernia as the outcome. The study included 261 patients (191 OAPR and 70 LAPR). Intraoperative blood loss (596.0 ± 633.4 vs. 307.0 ± 307.2 mL, p

Summary Surgical resection followed by adjuvant chemotherapy is the standard of care for patients with stage III colon cancer. To shorten the time interval between surgery and chemotherapy in patients with colon cancer, we instituted a standardized referral pathway. Evaluation of the intervention demonstrated that referring our patients with colon cancer to a medical oncologist earlier in the treatment process increased the number of patients in whom chemotherapy was initiated within 8 weeks compared with historical controls. These results support early medical oncology referral at institutions where delays in adjuvant chemotherapy initiation exist.

Transanal endoscopic microsurgery (TEM) is the treatment of choice for benign rectal tumors and select early rectal cancers. This surgical approach has become ubiquitous and surgeons are seeing recurrent lesions after TEM resection. This study aims to outline the safety and outcomes of repeat TEM when compared to primary TEM procedures. At St. Paul’s Hospital, demographic, surgical, pathologic, and follow-up data for patients treated by TEM are maintained in a prospectively populated database. Two groups were established for comparison: patients undergoing first TEM procedure (TEM-P) and patients undergoing repeat TEM procedure (TEM-R). Between 2007 and 2017, 669 patients had their first TEM procedure. Over this time frame, 57 of these patients required repeat TEM procedures, including 15 of these patients treated by 3 or more TEMs. Indications for repeat TEM included recurrence (78%), positive margins (15%), and metachronous lesions (7%). There were no differences between the groups in patient age, gender, or tumor histology. Compared to TEM-P, TEM-R had shorter operative times (38 vs. 52 min, p

Aim Perianal sepsis in Crohn's disease (CD) fistulas is managed with antibiotics and surgical drainage; a noncutting seton is used for an identified transsphincteric fistula tract. The optimal management following seton placement for initial control of perianal sepsis remains to be determined. Our main aim was to assess the success rates of curative surgery, seton removal or long-term indwelling seton in patients with and without CD. Method This was a retrospective cohort of consecutive patients with a perianal fistula treated with a noncutting seton between 2010 and 2019, including 83 CD patients and 94 patients without CD. Initial control of symptomatic perianal infection with a seton and subsequent healing and reintervention rates were compared between the three postseton management strategies. Results A total of 177 patients, 61% male and 83.1% with complex fistulas, were followed for a median of 23 months (interquartile range 11-40 months). Immunomodulatory treatment was used in 90.4% of CD patients after seton placement. Good initial control of perianal infection was achieved with a seton in CD and non-CD patients, at 92.9% and 96.7%, respectively (p = 0.11). Overall fistula healing or control for CD and non-CD patients was, respectively, 64% and 86% (p = 0.1) after curative surgery, 49% and 71% after seton removal (p = 0.21) and 58% and 50% with long-term seton placement (p = 0.72). Overall reintervention for recurrence was 83% in CD versus 53.1% in non-CD patients during the follow-up period (p = 0.002). Conclusion Definitive surgery was possible in only a minority of CD patients. Long-term seton management was an effective option in patients with CD with acceptable improvement and recurrence rates.

Background Transanal total mesorectal excision (TaTME) is an innovative technique for distal rectal cancer dissection. It has been shown to have similar short-term outcomes to conventional open and laparoscopic total mesorectal excision (cTME), but recent studies have raised concern about increased morbidity and local recurrence rates. The aim of this study was to assess outcomes after TaTME versus cTME for rectal cancer. Methods TaTME was implemented in 2014 using IDEAL principles in a single institution. The institution maintains databases for all patients undergoing rectal cancer surgery. This retrospective review compared data collected from all patients who had TaTME with those from a propensity-matched cohort of patients who underwent cTME. The primary outcome was a composite pathological measure combining margin status and quality of total mesorectal excision (TME). Short-term clinical and survival outcomes were also measured. Results Propensity matching created 109 matched pairs for analysis. Nine patients (8.3 per cent) undergoing TaTME had positive margins and/or incomplete TME, compared with 11 (10.5 per cent) undergoing cTME (P = 0.65). There were no significant differences in morbidity between the TaTME and cTME groups, including number of anastomotic leaks (13.8 versus 18.3 per cent; P = 0.37). The estimated 3-year local recurrence-free survival rate was 96.3 per cent in both groups (P = 0.39). Estimated 3-year overall (93.6 per cent for TaTME versus 94.5 per cent for cTME; P = 0.09) and disease-free (88.1 versus 76.1 per cent; P = 0.90) survival rates were similar. Conclusion TaTME provided similar outcomes to cTME for rectal cancer with the application of IDEAL principles., This study assessed the outcomes of a single-institution prospectively collected cohort of patients undergoing transanal total mesorectal excision (TaTME) for rectal cancer, compared with a propensity-matched cohort of patients undergoing conventional surgery. Methods from the IDEAL framework were used to institute TaTME. There were no significant differences in histopathological, clinical or survival outcomes between the two groups.

BACKGROUND The role of MRI-detected EMVI (mrEMVI) as a reliable prognostic factor in rectal cancer has been emphasized in recent years but this finding remains underreported by many institutions. OBJECTIVE This review aimed to demonstrate the importance of pre- and post-treatment MRI-detected EMVI as independent prognostic factors of adverse oncologic outcomes in patients undergoing neoadjuvant therapy followed by total mesorectal excision. METHODS This review was designed using the PRISMA guidelines. The following electronic databases were searched from January 2002 to January 2020: CENTRAL, Ovid MEDLINE, PubMed and Ovid Embase. Main outcomes included disease-free survival (DFS) and overall survival (OS). Other outcomes of interest comprised positive resection margin and synchronous metastases. RESULTS Seventeen studies involving a total of 3821 patients were included for data synthesis. For pre-neoadjuvant treatment mrEMVI, pooled hazard ratio (HR) estimate for DFS was 2.30 (95%CI 1.54-3.44) for higher recurrence in mrEMVI-positive patients. mrEMVI-positive patients were found to have a lower OS with a pooled HR of 1.68 (95%CI 1.27-2.22). Pooled risk ratio (RR) for synchronous metastasis was 4.11 (95%CI 2.80-6.02) for mrEMVI-positivity. For post-neoadjuvant treatment EMVI (ymrEMVI), positive status showed a lower DFS with a pooled HR of 2.04 (95%CI 1.55-2.69). RR of having a positive resection margin status was 2.95 (95%CI 1.75-4.98) for ymrEMVI-positive patients. CONCLUSION This review showed that oncologic outcomes are significantly worse for both pre- and post-neoadjuvant treatment mrEMVI-positive patients. MRI-detected EMVI should be consistently reported in rectal cancer staging and may provide guidance for the targeted use of additional systemic therapy.

Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

In patients treated by transanal endoscopic microsurgery (TEM), breach of the peritoneal cavity is a feared intraoperative challenge. Our aim is to analyze predictors and short-term outcomes of patients with peritoneal perforation (TEM-P) when compared to similar patients with no peritoneal compromise (TEM-N). At St. Paul’s Hospital, demographic, surgical, pathologic, and follow-up data for all patients treated by TEM is maintained in a prospectively populated database. A retrospective review was performed and two groups were established for comparison: TEM-P and TEM-N. Statistical analysis was performed using student’s t or chi-squared test, where appropriate. Of 619 patients treated by TEM between 2007 and 2016, 39 (6%) patients were in the TEM-P group and 580 (94%) in the TEM-N group. There were no differences between the groups in patient age, gender, histology, or tumor size. Patients who had peritoneal perforations had more proximal lesions (11 vs. 7 cm, p

ERUS and MRI are used for preoperative imaging of rectal cancer. Here, we compare ERUS and MRI for accuracy of CRM prediction at mid- and distal rectal locations. In retrospective review, 20 rectal cancer patients having TME surgery had both ERUS and MRI preoperatively: 8 mid rectum and 12 in distal rectum. Predicted CRM by ERUS and MRI were compared to TME pathology. Overall, predicted CRM was 6.5 ± 3.6 mm by ERUS, 7.7 ± 5.0 mm by MRI, and 6.0 ± 4.6 mm by pathology. Overall, correlation coefficients to pathology were 0.77 (p = 0.0004) for ERUS and 0.64 (p = 0.008) for MRI. In distal rectum, correlation coefficients were 0.71 (p = 0.02) for ERUS and −0.10 (p = 0.79) for MRI. In mid rectum, correlation coefficients were 0.92 (p = 0.01) for ERUS and 0.44 (p = 0.38) for MRI. While MRI is used routinely for preoperative rectal cancer imaging, ERUS can provide additional assessment of CRM for mid or distal rectal lesions. Further investigation is needed to support these preliminary ERUS CRM findings in mid and distal rectum.

Background The relationship between hospital volume and patient outcomes remains controversial for rectal cancer. Methods This is a population-based database study. Patients treated with surgery for a stage I to III rectal adenocarcinoma from 2003 to 2009 were identified. High-volume hospitals (HVH) were those centers performing 20 surgeries or more per year. Primary outcomes were operative and perioperative factors that have proven influence on patient outcomes. Results In all, 2,081 patients had surgery for rectal cancer. Of these, 1,690 patients had surgery in an HVH and 391 had surgery in a low-volume hospital. On multivariate analysis, patients who had surgery in an HVH were more likely to have sphincter-preserving surgery, 12 or more lymph nodes removed with the tumor, neoadjuvant radiation therapy, and receive pre-operative or postoperative chemotherapy. Conclusions For rectal cancer patients in British Columbia, Canada, being treated at an HVH is associated with several quality indicators linked to better patient outcomes.

Objective: The aim of this study was to determine the incidence of, and preoperative risk factors for, positive circumferential resection margin (CRM) after transanal total mesorectal excision (TaTME). Background: TaTME has the potential to further reduce the rate of positive CRM for patients with low rectal cancer, thereby improving oncological outcome. Methods: A prospective registry-based study including all cases recorded on the international TaTME registry between July 2014 and January 2018 was performed. Endpoints were the incidence of, and predictive factors for, positive CRM. Univariate and multivariate logistic regressions were performed, and factors for positive CRM were then assessed by formulating a predictive model. Results: In total, 2653 patients undergoing TaTME for rectal cancer were included. The incidence of positive CRM was 107 (4.0%). In multivariate logistic regression analysis, a positive CRM after TaTME was significantly associated with tumors located up to 1 cm from the anorectal junction, anterior tumors, cT4 tumors, extra-mural venous invasion (EMVI), and threatened or involved CRM on baseline MRI (odds ratios 2.09, 1.66, 1.93, 1.94, and 1.72, respectively). The predictive model showed adequate discrimination (area under the receiver-operating characteristic curve >0.70), and predicted a 28% risk of positive CRM if all risk factors were present. Conclusion: Five preoperative tumor-related characteristics had an adverse effect on CRM involvement after TaTME. The predicted risk of positive CRM after TaTME for a specific patient can be calculated preoperatively with the proposed model and may help guide patient selection for optimal treatment and enhance a tailored treatment approach to further optimize oncological outcomes.

Transanal endoscopic surgery is the treatment of choice in patients with rectal adenomas that cannot be removed by endoscopy. However, the risk of adenoma recurrence and optimal surveillance is not well defined. The objective of this study was to characterize the timing and frequency of rectal adenoma recurrence after removal by transanal endoscopic surgery and identify recurrence risk factors. This was a retrospective cohort study of a large, single-center academic institution in Vancouver, BC, Canada. Consecutive patients between May 1, 2007 and September 30, 2016 with pathology-confirmed rectal adenoma treated by primary excision with transanal endoscopic surgery and at least 1 year of confirmed endoscopic follow-up were included. Main outcome measures were recurrence rates following TEM as well as risk factors for recurrence. 297 patients met inclusion criteria. The mean age of patients was 66.5 ± 11.5 years and 57.9% were male. Median follow-up was 623 (range 56–3841) days. A total of 62 recurrences occurred in 41 patients (13.8% of study population). Recurrences were managed with repeat transanal endoscopic surgery or endoscopic resection 67.7% and 25.8% of the time, respectively. Radical resection was required for adenocarcinoma in 4 patients. Recurrence-free survival rates were 93.4% at 1 year, 86.2% at 2 years, and 73.1% at 5 years. After adjusting for individual surgeons, adenoma height, size > 3 cm, high-grade dysplasia, positive margins, and management of the rectal defect, patients who underwent surgery in the latter 5 years of the study had lower odds of recurrence (OR 0.42, 95% CI 0.19, 0.93, p = 0.03). Rectal adenomas managed by transanal endoscopic surgery are lesions at high risk for recurrence; surveillance should be performed within the first 2 years and continued for a total of at least 5 years. Most recurrences can be successfully treated with repeat TEM or endoscopic resection.

To determine whether closure of the defect created during full thickness excision of a rectal lesion with transanal endoscopic microsurgery (TEM) leads to fewer complications when compared to leaving the defect unsutured. This is a single-center cohort study using a prospectively maintained database. All patients ≥18 years old treated with full thickness TEM with no compromise of the peritoneal cavity were included. Two cohorts were established: patients with the defect sutured and patients with the defect left open. Demographic, operative, and pathologic data were compared. The main outcome analyzed was early (

Background High urinary infection (UTI) rate (12%) for our rectal surgery prompted practice change to early catheter removal (postoperative day 2) and prophylactic tamsulosin. Here we report urinary retention (UR) and UTI after this change. Methods Retrospective cohort study in male patients 50+ years undergoing elective colorectal surgery from July 2015 to July 2017. Multivariate regression was used to determine risk factors for urinary retention. Results 157 patients, 57 without and 100 with tamsulosin had UR 11.46% and UTI 5.13%. Of all potential risk factors, ileus (OR 5.50, 95% CI: 1.86–16.24) was an independent risk factor for urinary retention. Conclusions Urinary retention of 11% after colorectal resection is within literature range and associated with post-operative ileus. Tamsulosin did not affect UR in our small study sample. Early catheter removal was associated with decreased UTI rate.

Background Cyclo-oxygenase-2 (COX-2), an inducible enzyme expressed in areas of inflammation, is a target of interest for colorectal cancer therapy. Currently, the predictive significance of COX-2 in colorectal cancer remains unclear. Methods Tissue microarrays were constructed using 118 colon cancer and 85 rectal cancer specimens; 44 synchronous metastatic colon cancer and 22 rectal cancer lymph nodes were also evaluated. COX-2 expression was assessed by immunohistochemistry. Univariate analysis was used to determine the predictive significance of clinicopathologic variables. Overall survival, disease-specific survival, and disease-free survival were the main outcomes examined. Results COX-2 was found to be expressed in 93% of colon cancers and 87% of rectal cancers. Decreased COX-2 expression was related to decreased disease-specific survival ( P = .016) and decreased disease-free survival ( P = .019) in the rectal cancer cohort but not in the colon cancer cohort. Conclusions COX-2 expression has predictive utility for management of rectal but not colon cancer.

Background A diverting stoma is an accepted adjunct to low anterior resection (LAR) for rectal cancer. However, some patients do not undergo a subsequent procedure to have the stoma reversed. We aim to determine incidence and risk factors for nonclosure of the diverting stoma. Methods This is a retrospective study of stage I to III rectal cancer patients at a single institution having LAR with curative intent and a diverting stoma. Results We studied 162 patients. Prevalence of nonclosure of the temporary stoma was 14.5% within 13 months of the index surgery. On a multivariate linear regression model, nonclosure was associated with anastomotic leak (odds ratio 9.89, 2.31 to 43.93, P P Conclusions Prevalence of nonclosure of a diverting stoma after LAR for rectal cancer is substantial (14.5%). Patients should be counselled regarding this risk with particular attention to potential risk factors.

BACKGROUND Stage for stage, rectal cancer has historically been associated with inferior survival compared with colon cancer. Randomized trials of rectal cancer have generally demonstrated improvements in locoregional relapse but not survival. OBJECTIVE We compared therapy and outcomes of colon versus rectal cancer in 2 time cohorts to determine if relative improvements have occurred. PATIENTS AND METHODS Patients with resected stage II/III colorectal cancer referred to the British Columbia Cancer Agency in 1989/1990 and 2001/2002 were identified. The higher of clinical or pathologic stage was used for patients receiving preoperative chemoradiation. Disease-specific survival (DSS) and overall survival (OS) were compared for rectal and colon cancer between the 2 cohorts. Kaplan-Meier method was used for survival analysis. RESULTS A total of 1427 patients were included, with 375 from 1989/1990 and 1052 from 2001/2002. Between 1989/1990 and 2001/2002 there were significant increases in the use of perioperative chemotherapy for both rectal and colon cancer (P

The American Society of Colon and Rectal Surgeons is dedicated to assuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Standards Committee is composed of Society members who are chosen because they have demonstrated expertise in the specialty of colon and rectal surgery. This Committee was created to lead international efforts in defining quality care for conditions related to the colon, rectum, and anus. This is accompanied by developing Clinical Practice Guidelines based on the best available evidence. These guidelines are inclusive, and not prescriptive. Their purpose is to provide information on which decisions can be made, rather than dictate a specific form of treatment. These guidelines are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these guidelines. It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.

Crohn’s disease (CD) is a complex disorder with important incidence in North America. Perianal fistulas occur in about 20% of patients with CD and are almost always classified as complex fistulas. Conventional treatment options have shown different success rates, yet there are data indicating that these approaches cannot achieve total cure and may not improve quality of life of these patients. Fibrin glue, fistula plug, topical tacrolimus, local injection of infliximab, and use of hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) are newly suggested therapies with variable success rates. Here, we aim to review these novel therapies for the treatment of complex fistulizing CD. Although initial results are promising, randomized studies are needed to prove efficacy of these approaches in curing fistulizing perianal CD.

PURPOSE: In a strategy aimed to improve perioperative and operative management of rectal cancer in British Columbia (BC), a series of educational events were provided for BC surgeons, radiation oncologists, and pathologists including teaching on the use of preoperative radiation, surgical technique with total mesorectal excision (TME), and pathology reporting. Seminars were offered during 2002 and 2003 each over 2 days with documented attendance from 30 hospitals in the province. We wished to determine whether frequency of preoperative radiation and TME surgery changed on a population level after the rectal cancer education courses in 2002 and 2003. METHODS: All patients were referred to the BC Cancer Agency, the only center for radiation in BC. Treatments and data were abstracted from the Colorectal Cancer Outcomes Unit database. Patients with resected stage I to III rectal cancer were included who were diagnosed before (2000-2001) and after (2004) the education courses. We used changes from 2000 to 2001 to reflect effects of sporadic continued medical education (CME) compared with effects of formal systematic provincial education courses (changes from 2001 to 2004). RESULTS: A total of 778 eligible patients were included from 2000 (n = 264), 2001 (n = 202), and 2004 (n = 312). The percentage of stage III patients was similar in the 3 time periods. The use of preoperative radiation therapy increased significantly over time, 43% (114/264), 56% (113/202), and 86% (268/312) (P < .0001). TME use also increased significantly, 35%, 44%, and 71% (P < .0001). CONCLUSIONS: The implementation of guidelines for the use of preoperative radiation and TME by formal systematic provincial education courses for surgeons, radiation oncologists, and pathologists resulted in significant improvements in rectal cancer management on a provincial level. Such programs may be more effective than "sporadic" CME, particularly in multidisciplinary and complex care settings like adjuvant rectal cancer therapy.

Clinical evaluation alone is still considered adequate by many clinicians who treat patients with appendicitis. The impact of computed tomography (CT) on clinical outcomes remains unclear, and there is no consensus regarding the appropriate use of CT in these patients. We sought to evaluate the impact of abdominal CT on the clinical outcomes of patients presenting with suspected appendicitis.We conducted a systematic review of the literature to identify studies that examined clinical outcomes related to the use of abdominal CT in the diagnosis of acute appendicitis. Inclusion criteria were studies of adult patients with suspected appendicitis that evaluated the impact of abdominal CT on negative appendectomy rates, perforation rates or time to surgery. Two independent investigators reviewed all titles and abstracts and extracted data from 28 full-text articles. Statistical analysis was conducted using Review Manager 5.0.10 software.The negative appendectomy rate was 8.7% when using CT compared with 16.7% when using clinical evaluation alone (p0.001). There was also a significantly lower negative appendectomy rate during the CT era compared with the pre-CT era (10.0% v. 21.5%, p0.001). Time to surgery was evaluated in 10 of the 28 studies, 5 of which demonstrated a significant increase in the time to surgery with the use of CT. Appendiceal perforation rates were unchanged by the use of CT (23.4% in the CT group v. 16.7% in the clinical evaluation group, p = 0.15). Similarly, the perforation rate during the CT era was not significantly different than that during the pre-CT era (20.0% v. 19.6%, p = 0.74).This meta-analysis supports the hypothesis that the use of preoperative abdominal CT is associated with lower negative appendectomy rates. The use of CT in the absence of an expedited imaging protocol may delay surgery, but this delay is not associated with increased appendiceal perforation rates. Routine CT in all patients presenting with suspected appendicitis could reduce the rate of unnecessary surgery without increasing morbidity.

BACKGROUND: To evaluate the expression pattern and prognostic significance of the type 1 growth factor receptor (T1GFR) family in colon carcinoma. METHODS: Tissue microarrays were constructed using 127 tumor samples and 47 metastatic lymph nodes and T1GFR family expression was determined by immunohistochemistry. Univariate and multivariate analyses examined clinicopathologic variables for prognostic significance, and the correlation between primary and lymph node expression was determined by Spearman correlation. RESULTS: Overexpression of HER-1, HER-2, HER-3, and HER-4 in tumor samples was 32%, 1%, 12%, and 37%, respectively, and 30%, 0%, 11%, and 24% in nodal samples, respectively. On multivariate analysis, positive margins, lymphatic invasion, and HER-3 expression were significant predictors of survival outcome. There was significant correlation between tumor and regional lymph node expression for the T1GFR family members. Tumor HER-3 expression was associated with lymphatic invasion and distant recurrence. CONCLUSIONS: Tumor HER-3 expression has prognostic utility in individuals with colon carcinoma. Correlation between tumor and lymph node expression of T1GFR family members suggests that tumor receptor status may guide targeted therapy selection.

Treatment of rectal cancer over the last two decades has evolved with changes in techniques of surgery and radiation based on national and international trials. Preoperative adjuvant radiation is now preferred over postoperative adjuvant radiation, and total mesorectal excision with preservation of pelvic nerves is the gold standard for surgical treatment of rectal cancer. Preservation of the anal sphincter without compromising oncological outcome is an additional benefit for patients with carcinoma in the distal rectum. Further progress in imaging and a multidisciplinary team approach will facilitate individualization of treatment strategy with more focus on quality of life.

Background A subset of patients with colon cancer staged by conventional methods have occult micrometastases and do not receive adjuvant chemotherapy. Sentinel lymph node (SLN) mapping and staining by immunohistochemistry is a technique that may identify such occult micrometastases, thereby upstaging patients with positive findings. The purpose of this study was to determine whether ex vivo SLN mapping in colon cancer could be applied successfully to patients at our institution. Methods Seventeen patients with intraperitoneal colon tumors undergoing resection were studied prospectively. SLNs were identified as the first blue stained node(s) after ex vivo peritumoral injection of isosulfan blue dye. Additional lymph nodes were harvested and processed in accordance with standard pathologic evaluation for colon cancer. All nodes were examined after routine hematoxylin and eosin (H&E) staining. SLNs that were negative on H&E were analyzed further by multilevel sectioning and immunohistochemistry staining using anticytokeratin monoclonal antibody. Results Of the 17 study patients, SLNs were identified in 16 (94%) cases. The SLN was the only positive node in 3 patients. An identified SLN was positive (by H&E) in all patients with associated positive non-SLN nodes. The average number of nodes retrieved per patient was 16 (range, 4–54). Overall, SLNs accurately reflected the status of the entire lymph node basin in 16 (94%) patients. Two (12%) patients with negative nodes by H&E potentially were upstaged after further SLN analysis. The negative predictive value for SLN mapping was 89%. Conclusions The ex vivo technique of SLN mapping for colon cancer is feasible. In the current study, SLN results were concordant with non-SLNs in the majority of patients. Furthermore, this technique may have upstaged 2 (12%) patients. Whether this ultimately will affect overall survival has yet to be determined.

Background Improved survival after injury has been demonstrated with trauma system implementation and designation of trauma centers. Local designating health authorities or national verification (United States) or accreditation (Canada) programs audit trauma center performance. The relative importance of designation versus accreditation with respect to improved outcomes is not clear. The purpose of this study was to measure outcomes within a single regional trauma system after designation of trauma centers and to compare outcomes in the one accredited center to the nonaccredited centers. Methods Data from three trauma centers were studied. All were large, university-affiliated regional medical centers, integrated into a regional trauma system and served by a single ambulance service. The study period was 1992 to 1999, immediately after trauma center designation in 1991. The British Columbia Trauma Registry was used to identify trauma patients, mechanism of injury, length of stay, case mix, case volume, acuity, pediatric caseload, and proportion of transfers at each center. A questionnaire was circulated to each hospital to determine the level of institutional support and programmatic development for trauma. The Trauma Registry was used to calculate z scores (TRISS methodology) for each center and TRISS-adjusted mortality odds ratios between institutions. Differences in covariables were controlled for in subgroup analysis. Results Two centers (hospitals A and C) had a high trauma caseload; one (hospital B) had a small and diminishing caseload. Only one center (hospital A) developed a trauma program consistent with Canadian accreditation criteria; z scores for center A were consistently better than at hospital B or C and survival odds ratios were significant. This finding applied to the total trauma population, blunt adult trauma patients (whether or not transfers and hip fracture patients were excluded), and in the more severely injured blunt trauma subgroups. There were no differences between hospitals for the relatively small number of patients with penetrating trauma. Conclusion Differences between hospitals were apparent from the outset of the trauma system. However, designation as a trauma center does not appear to necessarily improve survival in large regional medical centers. Development of a trauma program and commitment to meeting national guidelines through the accreditation process does appear to be associated with improved outcome after injury.

Linitis plastica refers to thickening, decreased motility, and increased rigidity of the wall of a hollow organ, classically the stomach. 1,2 This condition is caused by malignant infiltration of the wall associated with fibrosis and proliferation of connective tissue and may occur as a primary or secondary process. It rarely involves the colon but, when it does, is usually a manifestation of metastatic disease.3 The disease is notably difficult to diagnose, even when there is a history of carcinoma elsewhere. The mucosa may be spared and thus intact on endoscopic examination with subsequent negative superficial biopsy results. 2,4,5 Radiologically, linitis plastica may mimic primary (mucosal origin) rectal cancer, other inflammatory or ischemic processes, or postradiotherapy changes. 1,2,6 Barium-enhanced radiologic and computed tomographic findings are well described but are often nonspecific. 1,6 This case illustrates the features of linitis plastica on transrectal ultrasonography and how this technique, which is increasingly performed in the staging of rectal tumors, may suggest the correct diagnosis.

Rectal cancer patients' expectations of health and function may affect their disease- and treatment-related experience, but how patients form expectations of postsurgery function has received little study.We used a qualitative approach to explore patient expectations of outcomes related to bowel function after sphincter-preserving surgery for rectal cancer.This was a cohort study of patients who were about to undergo sphincter-preserving surgery for rectal cancer.The study was conducted through individual telephone interviews with participants.Twenty-six patients (14 men and 12 women) with clinical TNM stage I to III disease were enrolled.The semistructured interview script contained open-ended questions on patient expectations of postoperative bowel function and its perceived impact on daily function and life. Two researchers analyzed the interview transcripts for emergent themes using a grounded theory approach.Participant expectations of bowel function reflected 3 major themes: 1) information sources, 2) personal attitudes, and 3) expected outcomes. The expected outcomes theme contained references to specific symptoms and participants' descriptions of the certainty, importance, and imminence of expected outcomes. Despite multiple information sources and attempts at maintaining a positive personal attitude, participants expressed much uncertainty about their long-term bowel function. They were more focused on what they considered more important and imminent concerns about being cancer free and getting through surgery.This study was limited by context in terms of the timing of interviews (relative to the treatment course). The transferability to other contexts requires further study.Patient expectations of long-term functional outcomes cannot be considered outside of the overall context of the cancer experience and the relative importance and imminence of cancer- and treatment-related events. Recognizing the complexities of the expectation formation process offers opportunities to develop strategies to enhance patient education and appropriately manage expectations, attend to immediate and long-term concerns, and support patients through the treatment and recovery process.

We tested the hypothesis that endotoxemia and fasting are associated with increased gut apoptotic activity, gut permeability, and inflammation in a distant organ. Fed or fasted CD-1 mice were studied 6 h after intraperitoneal injection of either saline (sham) or endotoxin (4 mg/kg of 0111:B4 Escherichia coli lipopolysaccharide). We found that endotoxin increased gut caspase-3 and -6 activity by 4.9 ± 0.6- and 4.5 ± 0.5-fold, respectively ( P < 0.001), and increased terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) staining of mucosal cells ( P< 0.05). Feeding decreased caspase-3 activity by 40% ( P< 0.05) and decreased endotoxin-induced TUNEL staining ( P< 0.05). Endotoxin increased gut poly(ADP-ribose) polymerase activity by 15% ( P < 0.05). Endotoxin increased gut permeability by 44% ( P < 0.05), an effect reduced 36% by feeding ( P < 0.05). Similarly, endotoxin increased pulmonary neutrophil infiltration (6.0 ± 1.0-fold, P< 0.001) and increased lung interleukin (IL)-6 (5.9 ± 0.1-fold, P < 0.001) and macrophage inflammatory protein (MIP)-2 expression (290 ± 40-fold, P < 0.001), whereas feeding decreased this effect by 43% for neutrophils, 40% for IL-6 ( P < 0.05), and 35% for MIP-2 ( P < 0.05). Thus endotoxin increases gut apoptotic activity, gut permeability, and pulmonary inflammation. Enteral feeding may decrease the distant organ inflammation by reducing gut apoptosis, thereby maintaining gut mucosal function during endotoxemia.

Approximately 20% of patients with ulcerative colitis will require surgical treatment. Recent data suggest that infliximab may reduce the need for surgery in patients with severe ulcerative colitis. However, it is unclear whether data from these small trials will translate to reduced colectomy rates in populations with ulcerative colitis.The purpose of this study was to determine the impact of infliximab on the rates of colectomy for ulcerative colitis and the prescribing practices for infliximab in British Columbia, Canada.We retrospectively reviewed data from 4 province-wide population-based databases maintained by the British Columbia Ministry of Health, a central registry, a hospital separations file, a physician payment file, and a pharmaceutical file. Data were collected from April 1, 2001, to March 31, 2010.This investigation was conducted at the University of British Columbia.All patients aged 18 to 75 with ulcerative colitis were included and identified using a validated strategy with International Classification of Diseases 9/10 codes. Patients with severe ulcerative colitis were defined by treatment with a course of corticosteroids during the study period. Patients treated with infliximab were identified using the provincial pharmaceutical file.The primary outcome was surgery determined by an International Classification of Diseases 9/10 code for partial or total colectomy.Between 2001 and 2010, 7227 subjects were identified with ulcerative colitis. The number of subjects with severe ulcerative colitis was 2537. For general ulcerative colitis, rates of colectomy decreased from 9.97% to 8.88% in the preinfliximab era (2003-2004) and postinfliximab era (2008-2009; p = 0.03). For severe ulcerative colitis, there was no significant difference in colectomy rates (9.97% vs 11.14%; p = 0.18). The highest rate of infliximab prescription was found to be in the provincial health region that encompasses the tertiary academic centers of the province.Although the overall number of patients in this analysis is sizeable, the number of patients who were prescribed infliximab during the study period is relatively modest, which may have impacted trends.In the severe ulcerative colitis population, there has been no change in the colectomy rate over time despite the introduction of infliximab.

The objective of this study was to determine if timeliness of care would improve after implementation of the team approach in trauma management in a single teaching hospital. To make this determination, we used a before-and-after retrospective cohort series for a 550-bed teaching and tertiary referral hospital that was not a level 1 trauma center. We included all patients who presented to the Emergency Department and who were admitted to St. Paul's Hospital because of trauma during 2 baseline months (May and November 1987; n = 111) and 2 follow-up months (May and November 1990; n = 142). In 1988, a formal trauma team was developed to coordinate the care of trauma patients who were seen in the Emergency Department. Indications for calling the trauma team were based on the criteria of the American College of Surgeons for triage to a trauma center. We calculated elapsed time from assessment in the Emergency Department to arrival of the trauma surgeon, discharge from the Emergency Department, and arrival of the patient in the operating room (for urgent or emergent surgery). We also determined the Revised Trauma Score, the Injury Severity Score (1985 version), the crude mortality ratio, and the Z statistic (population outcome comparison). After implementation of the trauma team, median elapsed time from initial nursing assessment in the Emergency Department to arrival in the operating Room for blunt trauma patients decreased from 11.33 to 4.82 hours (P = .05), but there were no significant differences in any other measures of timeliness, crude mortality, or adjusted mortality. We conclude that implementation of a trauma team in a teaching hospital is associated with a minimal effect on timeliness of care for admitted trauma patients.

Total mesorectal excision with preoperative radiation and chemotherapy provide the lowest local recurrence rates for rectal cancer. Timing of surgery after preoperative chemoradiation is being increased to optimize tumor downstaging. In cases of complete clinical response from chemoradiation, permissive observation without resection is being investigated. Significant anorectal dysfunction results from low anterior resection and radiation. Good prognostic tumor characteristics are being investigated with the aim of selecting cases for whom preoperative radiation may be avoided. Preoperative and postoperative radiation provides improved local cancer control for superficial cancers removed by local excision.

Subcutaneous emphysema following laparoscopy could result in postoperative respiratory acidosis from prolonged CO2 absorption. We studied the magnitude and duration of alterations in PaCO2 coincident with direct CO2 insufflation into the subcutaneous fat of the anterior abdominal wall of 5 anesthetized juvenile pigs.First, each pig was insufflated with 6 L of CO2 to produce moderate emphysema over the trunk. Following return to baseline PaCO2, each pig was re-insufflated with 12 L of CO2 to produce severe emphysema over lower limbs, neck, head, and trunk. Measurements of arterial blood gases were performed every 5 or 10 min. Minute ventilation was held constant to represent the worst case scenario.From baseline PaCO2 of 41.8 +/- 2.3 mm Hg, PaCO2 peaked at 68.3 +/- 8.6 (P0.02) and 92.9 +/- 10.7 (P0.01) mm Hg for the 6- and 12-L volumes, respectively, 20 to 25 minutes following insufflation. From baseline arterial pH of 7.40 +/- 0.02, respective nadirs of pH were 7.21 +/- 0.06 (P0.02) and 7.08 +/- 0.05 (P0.01). PaCO2 and arterial pH took approximately 100 minutes to return to baseline after insufflation with both 6 and 12 L volumes.When minute ventilation is fixed, subcutaneous CO2 insufflation causes increased PaCO2 and decreased pH that may persist for a prolonged period of time. Therefore, patients with subcutaneous emphysema after laparoscopy should be observed in postanesthetic recovery until PaCO2 and pH approach baseline.

At present, pelvic phased array-coil MR is used as the validated imaging modality for measurement of the closest predicted radial mesorectal margin for rectal cancer. Endorectal ultrasound is also used to assess the clinical stage of the cancer that will determine the recommendation for neoadjuvant chemoradiation, but it has not been used to assess the closest predicted radial margin.We propose to assess endorectal ultrasound identification of mesorectal margins and the measurement of the closest predicted radial tumor-mesorectal margin.Patients included were those having MRI and endorectal ultrasound for evaluation of primary rectal cancer in 2010 at a tertiary cancer referral colorectal clinic. Clinical data, MRI, and endorectal ultrasound images were assessed. Two independent retrospective measurements of mesorectal dimensions were correlated to evaluate the reproducibility of identifying mesorectal margins. MRI and endorectal ultrasound images were compared for independent measurements of mesorectal dimensions and of the closest predicted radial mesorectal margin. MRI and endorectal ultrasound determination of margin involvement were assessed for agreement.Fifty-two patients were studied with an average rectal cancer distance to the anal verge of 6.8 cm. Interobserver correlation coefficients of endorectal ultrasound mesorectal dimensions ranged from 0.47 to 0.53 (p0.01). MR and endorectal ultrasound measurements of the closest predicted radial mesorectal margin were correlated r = 0.56 (p0.0001). MR and endorectal ultrasound determination of margin involvement agreed in 81% of cases.Endorectal ultrasound has substantial agreement with MR to measure the closest predicted radial tumor-mesorectal margin. Correlations between observers and modalities for identification of mesorectal dimensions are modest. Further assessment is indicated to confirm endorectal ultrasound mesorectal measurements in a larger sample and to understand the advantages and disadvantages relative to MR.

Randomized controlled trials have shown equivalent outcomes for laparoscopic-assisted colectomy (LAC) and open colectomy (OC) when performed by well-trained surgeons experienced in both techniques. Our goal was to evaluate the outcomes of LAC at a population level.Using the prospectively collected Gastrointestinal Cancer Outcomes Unit database from the British Columbia Cancer Agency, short- and long-term outcomes in patients with colon cancer treated with LAC and OC were compared from 2003 to 2008 inclusive.There was a statistically significant increase in the proportion of LAC from 2003 to 2008 (P.001). LAC was more likely to be performed in the elective setting (P.001) and for smaller tumors (P.001). A similar proportion of patients had a minimum of 12 lymph nodes identified by pathology (58% vs 60%, P = not significant). Disease-free survival was similar for the 2 groups after adjusting for stage, emergency presentation, and adjuvant chemotherapy. There was no difference in overall survival.The introduction of LAC for colon cancer in British Columbia outside of optimized clinical trial conditions appears to be effective and safe.

We tested a system of indirect calorimetry (Deltatrac Metabolic Monitor) for accuracy to measure oxygen consumption and sensitivity to detect small changes in oxygen consumption, in vitro, using a lung model simulation of ventilating patients who have stiff lungs. In vivo, we assessed reproducibility of the system to measure oxygen consumption in patients who had adult respiratory distress syndrome (ARDS) or sepsis. In vitro, oxygen consumptions of 100, 200, 300, and 500 mL/min were simulated by injecting N 2 into the lung model at 3-minute ventilations (10, 15, and 20 L/min) and at four levels of FIO 2 (0.40, 0.60, 0.70, and 0.80). After each baseline measurement, N 2 flow was increased to simulate an increase in VO 2 of 10% to 15%. At FIO 2 of 0.6 and 0.8, 15 cm H 2 O of positive end-expiratory pressure (PEEP) was applied to the lung model and measurements repeated. The Deltatrac had an average error of −2.1% (range, −7% to 3%). After simulated increases in oxygen consumption, the Deltatrac detected the change with an error less than 1% in all combinations tested. Although adding PEEP to the lung model altered accuracy of measurement, error was always less than 5%. We measured oxygen consumption in 27 ventilated and sedated patients who had severe ARDS or sepsis (FIO 2 , 0.60 ± 0.1; PEEP, 9 ± 3 cm H 2 O; static compliance, 27 ± 12 mL/cm H 2 O [mean ± SD]). Coefficient of variation for oxygen consumption was 4.6% ± 1.6%. Even at FIO 2 , 0.80 coefficient of variation was less than 6%. We conclude that this system of indirect calorimetry is accurate, sensitive, and reproducible to measure VO 2 in critically ill patients.

BACKGROUND: Short-course preoperative radiotherapy and total mesorectal excision have decreased local recurrence rates from rectal cancer. However, the effect of this radiotherapy on bowel function and quality of life in these patients is not well understood. METHODS: Between 1999 and 2004, 34 patients underwent low anterior resection and either short-course preoperative radiation (N = 24) or surgery alone (N = 10). Quality of life and bowel function were assessed using validated instruments: European Organization of Research and Treatment of Cancer Quality of Life questionnaires, Fecal Incontinence Quality of Life Scale, and the Memorial Sloan-Kettering Cancer Center Bowel Function Instrument. RESULTS: Patients treated with preoperative radiation had higher rates of fecal incontinence and showed a strong trend toward lower global quality-of-life scores. In addition, there was a trend toward worse bowel function in these patients. CONCLUSIONS: Patients treated with short-course preoperative radiotherapy had worse continence-related quality of life than patients treated with surgery alone for rectal cancer. Fecal incontinence has a negative effect on quality of life in these patients, causing difficulty with coping, lifestyle, and depression, and limiting daily activities. Validated instruments provide standardized assessment of bowel function and quality of life.

We have previously reported outcomes for all rectal cancers in BC in 1996. We found that our local recurrence rates and survival were suboptimal relative to current standards in recent literature.In this retrospective, population-based study, we report the influence of emergent presentation (obstruction, perforation, massive hemorrhage) on outcomes, types of surgical procedures and use of staging investigations, and use of adjuvant radiation and chemotherapy.There were 452 invasive adenocarcinomas of the rectum of which 45 were emergent and 407 nonemergent. Disease-specific survival at 4 years for emergent and nonemergent stage II cancers were 66% versus 80%, respectively, and for stage III cancers, 60% versus 73%, respectively (P0.04). Local recurrence rates at 4 years for emergent and nonemergent stage II cancers were 20% versus 15%, respectively, and for stage III cancers, 70% and 20%, respectively (P0.05). Surgical resection more frequently involved a stoma for emergent (60%) than for nonemergent (35%) cases (P0.01). Percent of patients having complete staging investigations were similar between emergent (42%) and nonemergent patients (39%). Adjuvant radiation was given in similar proportion to emergent (61%) and nonemergent (55%) patients. Adjuvant chemotherapy was given to a slightly higher proportion of emergent patients (63%) than nonemergent patients (43%).We conclude that outcome from rectal cancer management is worse for emergent than nonemergent presentation. Since there is no difference in use of staging investigations or adjuvant therapy, the difference in outcome is likely due to difference in surgical technique between emergent and nonemergent cases.

Purpose: Rectal cancer outcome depends on stage, technical aspects of surgical excision, and use of adjuvant chemoradiation. Here, we examine effects of positive resection margin and tumor distance from the anus in stage 2 and 3 cancers on 4-year disease-specific survival and recurrence. Methods: We reviewed all 495 rectal cancer patients registered in British Columbia in 1996. Results: There were 481 cases analyzed: 29 in situ, 134 stage 1, 107 stage 2, 100 stage 3, 83 stage 4, and 28 unknown stage. Survival was significantly affected by presence of positive resection margin in stage 2 and 3 cancers, P = 0.0001. Lower tumor distance from the anus for stage 2 and 3 cancers worsened survival, P = 0.0007, and overall recurrence, P =0.016, but not local recurrence, P = 0.11. Adjuvant postoperative combined radiation and chemotherapy in stage 2 and 3 cancers significantly improved survival, P = 0.070 and local recurrence, P = 0.018, but not overall recurrence, P = 0.19. Conclusions: Presence of positive resection margin and tumor distance from the anus affect survival, local recurrence, and overall recurrence. Adjuvant postoperative combined radiation and chemotherapy improved our outcomes. Our local recurrence rates for rectal cancers are worse than currently reported standards of less than 10%. Improved surgical excision and use of adjuvant preoperative radiation and chemotherapy may improve outcome.

BACKGROUND: Laparoscopic techniques are being increasingly used for retroperitoneal surgery. However, hemodynamic and ventilatory efforts of retroperitoneal carbon dioxide (CO 2 ) insufflation have not been studied. We hypothesized that differences in absorptive surface, anatomy, and compartment compliance could result in different hemodynamic and ventilatory effects between retroperitoneal and intraperitoneal insufflation. METHODS: Pigs (n = 7) were anesthetized and stabilized. The peritoneal cavity was incrementally insufflated with CO 2 to a maximum pressure of 25 cm H 2 O and the gas released. Hemodynamics and arterial blood gas values were recorded initially, at each level of insufflation, and following the pneumoperitoneum release until baseline values were reached. This insufflation protocol was repeated in the retroperitoneum. RESULTS: Mean arterial pressure (111 mm Hg, 95% confidence interval 99 to 156) and cardiac output (3.7 L/min, 2.8 to 5.2) did not change with increasing insufflation pressure of either intraperitoneum or retroperitoneum. PaCO 2 was directly related to insufflation pressure in both spaces, increasing from 41.2 mm Hg (37.3 to 43.4) at baseline to 57.7 mm Hg (47.6 to 82.1) at insufflation pressure of 25 cm H 2 O. After release of the insufflation gas, time to return to baseline PaCO 2 was slightly less from the retroperitoneal space (73 minutes, 45 to 105) than the intraperitoneal (107 minutes, 35 to 175). CONCLUSIONS: The effects of CO 2 insufflation on hemodynamics and PaCO 2 are the same in the retroperitoneal and intraperitoneal spaces.

We asked whether crystalloid administration improves tissue oxygen extraction in endotoxicosis. Four groups of anesthetized pigs ( n = 8/group) received either normal saline infusion or no saline and either endotoxin or no endotoxin. We measured whole body (WB) and gut oxygen delivery and consumption during hemorrhage to determine the critical oxygen extraction ratio ([Formula: see text]). Just after onset of ischemia (critical oxygen delivery rate), gut was removed for determination of area fraction of interstitial edema and capillary hematocrit. Radiolabeled microspheres were used to determine erythrocyte transit time for the gut. Endotoxin decreased WB[Formula: see text](0.82 ± 0.06 to 0.55 ± 0.08, P < 0.05) and gut[Formula: see text](0.77 ± 0.07 to 0.52 ± 0.06, P< 0.05). Unexpectedly, saline administration also decreased WB[Formula: see text](0.82 ± 0.06 to 0.62 ± 0.08, P< 0.05) and gut[Formula: see text](0.77 ± 0.07 to 0.67 ± 0.06, P< 0.05) in nonendotoxin pigs. Saline administration increased the area fraction of interstitial space ( P< 0.05) and resulted in arterial hemodilution ( P < 0.05) but not capillary hemodilution ( P > 0.05). Saline increased the relative dispersion of erythrocyte transit times from 0.33 ± 0.08 to 0.72 ± 0.53 ( P< 0.05). Thus saline administration impairs tissue oxygen extraction possibly by increasing interstitial edema or increasing heterogeneity of microvascular erythrocyte transit times.

The use of helium for insufflation during laparoscopic surgery avoids hypercarbia and acidosis associated with absorbed CO2, but the effects of helium gas embolism are unknown. We compared the effects of CO2 with He gas embolism on survival, haemodynamic variables, oxygenation, and ventilation in pigs.Anaesthetized juvenile pigs were given progressively larger boluses of either CO2 (n = 5) or He (n = 4) into the right atrium. Measurements of haemodynamic variables, oxygenation, and PETCO2 were made before and after each gas injection.All animals survived injection of 300 ml CO2 while no animal survived more than 120 ml He (P0.01). Mean arterial pressure decreased more after 60 ml He (99 +/- 14 to 44 +/- 20 mmHg) than after 60 ml CO2 (110 +/- 12 to 88 +/- 14 mmHg, P0.001). Cardiac output did not change at any injection volume. The PETCO2 decreased more after 60 ml He (30 +/- 2 to 3 +/- 6 mmHg) than after 60 ml CO2 (35 +/- 3 to 30 +/- 3 mmHg, P0.001). Only the He group showed a decrease in PaO2 (190 +/- 51 to 68 +/- 22 mmHg at 60 ml, P0.05).Helium gas embolism has a greater deleterious effect than CO2 gas embolism on survival, MAP, PETCO2, and PaO2. These different effects of gas embolism should be recognized when considering the use of helium or other insoluble gases for abdominal laparoscopic insufflation.

In Reply. —Drs Bredle and Reinhart contend that our data do not refute the approach of increasing Do 2 to supranormal levels in critically ill patients to increase Vo 2 and hopefully improve outcome. They are right. Our study was not designed to test this hypothesis. However, our study and others have more clearly delineated the relationship between Do 2 and Vo 2 in humans and demonstrated that the rationale for increasing Do 2 to supranormal levels is based on an incorrect understanding of this relationship. The technique of increasing Do 2 to supranormal levels in critically ill patients has been based on the rationale that tissue hypoxia is present despite aggressive early resuscitation and return of adequate tissue perfusion according to traditional clinical and laboratory measurement. The presence of tissue hypoxia in these patients has been inferred from finding a correlation between Do 2 and Vo 2 when Do