The implementation of a transanal endoscopic microsurgery programme: initial experience with surgical performance.

AIM: Despite transanal endoscopic microsurgery (TEM) being used for over 30 years, there has been slow adoption of this modality in many centres. There remains a paucity of research regarding the learning curve and early performance of surgeons who begin to offer TEM. We sought to determine predictors of longer rates of tumour excision and improvements in operative time in a newly established TEM programme. METHOD: All patients who underwent TEM at the Ottawa Hospital, Ottawa, Canada, between October 2009 and September 2014 were included. Data were abstracted through a retrospective chart review. The average rate of lesion excision (ARE) was calculated to standardize the operation time by size of the pathological specimen (min/cm3 ), representing a measure of surgical efficiency. Surgical efficiency was plotted using restricted cubic splines. Predictors of higher ARE were determined using multivariable regression. RESULTS: During the study period 108 patients underwent TEM. ARE was available for 95 patients of mean age 67.2 years. The mean ARE was 18.6 min/cm3 . On adjusting for important covariates, the ARE improved with each additional case until 16 cases were completed. Significant predictors of higher ARE on multivariable analysis were age < 50 years, experience of fewer than five cases, and carcinoid/gastrointestinal stromal tumour or scar histology. CONCLUSION: Operative efficiency appears to improve as surgeons completed 16 TEM cases. We have identified important factors that result in longer operating time. The study has important implications with regard to surgical training and operative planning for new TEM programmes.

Exploring a "community of practice" methodology as a regional platform for large-scale collaboration in cancer surgery-the Ottawa approach.

Pressing challenges have forced health care providers to rethink traditional silos and professional boundaries. Communities of practice (cops) have been identified as a means to share knowledge across silos and boundaries. However, clarity sufficient to enable their easy and uniform reproducibility is lacking, leading to a gap between cop conceptualization and implementation. This paper explores a cop structure and outlines a framework that is adaptable, measurable, and implementable across health disciplines in a regional cancer surgery program.

Piloting a regional collaborative in cancer surgery using a "community of practice" model.

BACKGROUND: Patients requiring assessment for cancer surgery encounter a complex series of steps in their cancer journey. Further complicating the process is the fact that care is often delivered in a fragmented, silo-based system. Isolated strategies to improve cancer outcomes within those systems have had inconsistent results. METHODS: A regional quality improvement collaborative was developed based on a community of practice (cop) platform, a hub-and-spoke infrastructure, and a regional steering committee linking cop improvement projects with affiliated hospitals and their strategic priorities. The cop provided an avenue for multidisciplinary teams to collect and compare their performance data and to institute regional standards through literature review, discussion, and consensus. Regional interdisciplinary teams developed a set of quality indicators linked to mutually agreed-upon care standards. A limited regional database supported feedback about performance against both provincial and regional standards. RESULTS: The cop approach helped to develop a multihospital collaboration that facilitated care quality improvements on a regional scale, with clinical outcomes of the improvements able to be measured. The 9 participating hospitals delivered cancer surgery in the specific disease sites according to practitioner-developed and provincially- or regionally-generated care standards and clinical pathways. Compliance with provincial evidence-based clinical guidelines improved (20% increase in 2010-2011 compared with 2006-2007). Other significant improvements included standardization and implementation of regional perioperative pathways in breast, colorectal, and prostate cancer disease sites; rectal cancer surgery centralization; increased use of sentinel lymph node biopsies in breast cancer surgery; and decreased positive surgical margin rates in prostate cancer. CONCLUSIONS: Improved quality is likely a result of diverse confounding factors. The deliberately cultivated multihospital multidisciplinary cops have contributed to positive structural and functional change in cancer surgery in the region. This regional cop model has the potential to play an important role in the development of successful collaborations in care quality improvement.

Trends in colon cancer surgery in Ontario: 2002-2009.

AIM: The safety and efficacy of laparoscopic surgery for colon cancer is well established but its uptake in the province has not been previously explored. We report an investigation of the trends of open and laparoscopic surgery for colon cancer in Ontario, Canada. METHOD: A retrospective cross-sectional time-series analysis examining population-based rates of elective surgery for colon cancer among 10.5 million adults in Ontario was conducted from 1 April 2002 to 31 March 2009. Databases were linked to assess quarterly elective procedure rates over time. RESULTS: During the study period, 3950 laparoscopic and 13 048 open elective colon cancer operations were performed in Ontario. The overall quarterly rate of colon cancer surgery remained stable at an average of 5.8 per 100000 population (P=0.10). From the first and last quarter, the rate of laparoscopic operations increased nearly threefold from 0.8 to 2.2 per 100000 population with a notable increase after 2005 (P<0.01). In contrast, open surgery decreased by more than 30% from 5.3 to 3.5 per 100 000 population (P<0.01). If current trends continue, the projected proportion of laparoscopic colon operations is estimated to reach 41% by 2015. Patients receiving open surgery had a significantly higher preoperative comorbidity (Charlson comorbidity score≥3) than those having laparoscopy (47.8%vs 39.1%, standardized difference 0.26). CONCLUSION: Trends in Ontario of laparoscopic colon cancer surgery show an increase between 2002 and 2009, but the incidence remains lower than for open surgery.

Changing trends in rectal cancer surgery in Ontario: 2002-2009.

AIM: The safety and efficacy of laparoscopic surgery for colon cancer have been demonstrated in large, multicentre clinical trials. The study aimed to determine the use of laparoscopic surgery for rectal cancer in Ontario over a 7-year period. METHOD: We conducted a retrospective study examining rates of elective rectal cancer surgery among 10.5 million adults in Ontario, Canada, from 1 April 2002 to 31 March 2009. We linked the Canadian Institute for Health Information Discharge Abstract Database, the Registered Persons Database and the database of the Ontario Cancer Registry to assess procedures used over the period. Data on demographics were collected. Trends were assessed using time series analysis. RESULTS: Over the 7-year period, 8189 open and 1079 laparoscopic elective operations for rectal cancer were identified. The annual rate of laparoscopic rectal cancer procedures increased from 0.60 per 100,000 population in 2003 to 2.24 per 100,000 population in 2008 (P < 0.01). Laparoscopic patients were similar to open with respect to age (66.5 ± 11.8 vs 66.2 ± 12.1 years; standardized difference 0.02), gender (63.2%vs 59.4%; standardized difference 0.08), Charlson Comorbidity Index score (standardized difference < 0.1) and socioeconomic status (standardized difference < 0.1). CONCLUSION: Laparoscopic rectal cancer surgery rates are increasing in Ontario. Ongoing research regarding the long-term safety and effectiveness of the laparoscopic approach for rectal cancer surgeries may lead to greater increases in its utilization.

Panniculectomy: an alternative approach to the revision of a difficult stoma.

AIM: We describe a modified abdominoplasty technique as an alternative approach to the revision of a difficult stoma. METHOD: A patient with a retracted colostomy secondary to change in abdominal wall contour following significant weight loss was treated with this technique. The patient had previous colostomy revision with marlex mesh insertion for combined parastomal and massive ventral hernia repair. A preoperatively marked crescent shaped left upper quadrant segment of skin and subcutaneous fat was excised and the defect was approximated in multiple layers. This shifted the stoma opening cephalad and eliminated the cutaneous crease that originally made it difficult to obtain a proper stoma seal. RESULTS: At one year follow up the patient was extremely satisfied with the results and was able to properly pouch the stoma. CONCLUSION: Modified abdominoplasty can be used as an alternative, low morbid approach in dealing with selected patients with difficult stoma problems.

Rectal cancer: current surgical management.

Since the description of the abdominoperineal resection by W. Ernest Miles in 1908 and total mesorectal excision by Heald et al. in 1982, rectal cancer surgery continues to evolve. This evolution has not been limited to the surgical front. State-of-the-art imaging techniques allow us to stage more accurately the disease and modify our management accordingly. Advances in radiotherapy and chemotherapy have not only reduced local recurrence and improved survival rates in rectal cancer, but are also changing our surgical algorithm in approaching the disease. To achieve the best results, it is crucial to approach rectal cancer in a multidisciplinary fashion involving high volume surgeons, radiation and medical oncologists, radiologists, stoma therapists, and trained nurses in colorectal cancer care. Despite a low operative mortality, it is important to customize the approach to rectal cancer according to the patient's quality of life and life expectancy. This review will focus on current surgical management of rectal cancer and some of the newer advances in rectal cancer management.

Complications in laparoscopic intestinal surgery: prevention and management.

Laparoscopic surgery is rapidly becoming the standard of care for many intestinal disorders. Intraoperative complications of laparoscopic intestinal surgery have been described to occur in 4-16% of procedures, although definitions vary widely across reports. Complications associated with first trocar insertion, although rare, can be fatal. The use of an open insertion technique is strongly recommended. Other intraoperative complications associated with laparoscopic intestinal surgery include cautery injuries, vascular injuries and hemorrhage, bowel injuries, bladder and ureteric injuries as well as missed or delayed injuries. Physiolo-gical complications of laparoscopy include pneumoperitoneum-specific complications, cardiopulmonary complications, and position-related complications. Finally, injury to the surgeon can occur, from which the field of surgical ergonomics has been derived.

Laparoscopy influences hiring practices within academic surgical departments.

BACKGROUND: This study aimed to determine whether the increasing emphasis on minimally invasive surgery (MIS) influences hiring practices within academic surgical departments. METHODS: A questionnaire was mailed to chairs of surgery departments and divisions of general surgery at the 16 Canadian academic institutions. Nonresponders were identified and contacted directly. The survey consisted of 34 questions, including Likert scales, single answers, and multiple-choice questions. Data were collected on demographics, perceptions of MIS, and recruitment/hiring. At the time of the survey, two department chair positions were vacant. RESULTS: A response rate of 87% (26/30) was obtained, with representation from 94% of departments (15/16). Of those surveyed, 88% intend to increase the importance of MIS at their institution within 5 years, and 87% intend to achieve this objective through new hirings. Networking (73%) and retention of recent graduates (89%) were cited most frequently as recruitment strategies. Strengthening the division, research, and education were considered important or extremely important by more than 90% of the respondents with respect to recruitment goals, whereas strengthening MIS was considered important or extremely important by 50%. Within 5 years, surgical departments intend to hire a median of four general surgeons, 50% of whom will have formal MIS training. In comparison, over the past 10 years, only 25% of new recruits had formal MIS training. More than 90% of the respondents considered formal MIS fellowship, MIS fellowship plus a second fellowship, and proctorship to be adequate training for performing advanced MIS, whereas traditional methods were considered inadequate. Lack of operative time and resource issues were considered most limiting in the hiring of new MIS surgeons. CONCLUSION: Minimally invasive surgery is growing in importance within academic surgical departments, but it remains an intermediate recruitment priority. Formal MIS training appears to be important in the recruiting of new surgeons, whereas traditional training methods are considered inadequate.

Hand-assisted laparoscopic colorectal surgery: an evidence-based review.

Despite its increasing use by practitioners, laparoscopic colorectal surgery remains technically challenging. Hand-assisted laparoscopic colorectal surgery may represent a viable hybrid alternative approach to standard laparoscopy. Although few high-quality studies have been carried out, hand-assistance appears to reduce operative time when compared to straight laparoscopy for both left-sided segmental colonic and total colorectal resections. Moreover, hand-assistance appears to maintain the short-term benefits of laparoscopy, while affording the surgeon with the ability to carry out complex cases in a minimally invasive fashion. Data pertaining to the use of hand-assistance for rectal cancer surgery are currently lacking. One the whole, hand-assisted laparoscopic colorectal surgery appears to be a useful tool for the minimally invasive surgeon, one that is perhaps best thought of as an adjunct to simple laparoscopy.

Laparoscopic resection for colon cancer: would all patients benefit?

PURPOSE: This study was designed to assess whether the exclusion criteria used in the Clinical Outcomes of Surgical Therapy and Colon Cancer Laparoscopic or Open Resection trials affected the generalizability of their findings. METHODS: A prospective database of consecutive laparoscopic resections performed for colon cancer was reviewed. Patients were categorized into two groups: inclusion group and exclusion group, based on the selection criteria used in the Clinical Outcomes of Surgical Therapy and Colon Cancer Laparoscopic or Open Resection trials. Baseline and perioperative data were analyzed by using t-tests, Wilcoxon's rank-sum, chi-squared, and Fisher's exact test. Kaplan-Meier survival curves, followed by adjustment for tumor nodes metastasis stage and age utilizing a Cox proportional hazard model, were performed. RESULTS: The inclusion group had 221 patients and the exclusion group had 166 (median age and gender distribution were similar). The exclusion group had a higher conversion rate (23 vs. 11.3 percent; P=0.0023). There was no difference in intraoperative complications (9 percent for exclusion group vs. 8.6 percent for inclusion group; P=0.8), operative time (180 minutes for exclusion group vs.172 minutes for inclusion group; P=0.24), or postoperative complication rates (33.7 percent for exclusion group vs. 26 percent for inclusion group; P=0.13). No difference was detected in perioperative mortality rates, length of stay, days to diet as tolerated, and adjusted two-year survival. CONCLUSIONS: No differences were found in outcomes between the two groups in terms of operative/postoperative complications, length of stay, perioperative mortality, and two-year survival. It seems that all patients with colon cancer can potentially benefit from a laparoscopic approach.

Broad-based fellowships: a cornerstone of minimally invasive surgery education and dissemination.

Aware of the trends in surgery and of public demand, many residents completing a 5-year training program seek fellowships in minimally invasive surgery (MIS) because of inadequate exposure to advanced MIS during their residency. A survey was designed to evaluate the effectiveness of a broad-based fellowship in advanced laparoscopic surgery offered in an academic health science center. The questionnaire was mailed to all graduates. Data on demographics, comfort level with specific laparoscopic procedures, and opinions regarding the best methods of acquiring these skills were collected. Most of the surgeons entered the fellowship directly after residency. The majority of these surgeons are academic surgeons. Fellows performed a median of 187 cases by the end of their training and felt comfortable operating on foregut, hindgut, and end organ. A full year of training was found to be the best format for appropriate skill transfer. A broad-based MIS fellowship meets the needs of both academic and community surgeons desiring to perform advanced laparoscopic procedures.

Middle mediastinal parathyroid: diagnosis and surgical approach.

We report two cases of middle mediastinal parathyroid ectopia associated with chronic renal disease. In both patients the diagnosis was delayed and prolonged due to the unusual location of the ectopic parathyroid tissue. The surgical approach was in error in 1 patient and corrected during the second procedure. We describe the surgical technique for exposing and excising parathyroid tissue from this area.

Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor.

Chemotherapeutic agents produce cytotoxicity via induction of apoptosis and cell cycle arrest. Rapidly proliferating cells in the bone marrow and intestinal crypts are highly susceptible to chemotherapy, and damage to these cellular compartments may preclude maximally effective chemotherapy administration. Glucagon-like peptide (GLP)-2 is an enteroendocrine-derived regulatory peptide that inhibits crypt cell apoptosis after administration of agents that damage the intestinal epithelium. We report here that a human degradation-resistant GLP-2 analogue, h[Gly2]-GLP-2 significantly improves survival, reduces bacteremia, attenuates epithelial injury, and inhibits crypt apoptosis in the murine gastrointestinal tract after administration of topoisomerase I inhibitor irinotecan hydrochloride or the antimetabolite 5-fluorouracil. h[Gly2]-GLP-2 significantly improved survival and reduced weight loss but did not impair chemotherapy effectiveness in tumor-bearing mice treated with cyclical irinotecan. Furthermore, h[Gly2]-GLP-2 reduced chemotherapy-induced apoptosis, decreased activation of caspase-8 and -3, and inhibited poly(ADP-ribose) polymerase cleavage in heterologous cells transfected with the GLP-2 receptor. These observations demonstrate that the antiapoptotic effects of GLP-2 on intestinal crypt cells may be useful for the attenuation of chemotherapy-induced intestinal mucositis.

Adrenal cortical carcinoma.

Adrenal cortical carcinoma is a rare endocrine tumor, and complete surgical resection is the only potentially curative treatment. Accurate preoperative biochemical and radiographic evaluation of the patient who presents with an adrenal mass optimizes patient management and facilitates a complete margin-negative resection of the primary tumor--the most important prognostic variable for long-term survival. Response to mitotane or chemotherapy is modest in patients with advanced disease. It is hoped that an improved understanding of the molecular pathogenesis of this challenging tumor will lead to the development of novel treatment strategies.

The glucagon-like peptide-2 receptor mediates direct inhibition of cellular apoptosis via a cAMP-dependent protein kinase-independent pathway.

Glucagon and the glucagon-like peptides regulate metabolic functions via signaling through a glucagon receptor subfamily of G protein-coupled receptors. Activation of glucagon-like peptide-2 receptor (GLP-2R) signaling maintains the integrity of the intestinal epithelial mucosa via regulation of crypt cell proliferation. Because GLP-2 decreases mortality and reduces intestinal apoptosis in rodents after experimental injury, we examined whether GLP-2R signaling directly modifies the cellular response to external injury. We show here that activation of GLP-2R signaling inhibits cycloheximide-induced apoptosis in baby hamster kidney fibroblasts expressing a transfected GLP-2 receptor. GLP-2 reduced DNA fragmentation and improved cell survival, in association with reduced activation of caspase-3 and decreased poly(ADP-ribose) polymerase cleavage and reduced caspase-8 and caspase-9-like activities. Both GLP-2 and forskolin reduced mitochondrial cytochrome c release and decreased the cycloheximide-induced cleavage of caspase-3 in the presence or absence of the PKA inhibitor H-89. Similarly, GLP-2 increased cell survival following cycloheximide in the presence of the kinase inhibitors PD98054 and LY294002. These findings provide evidence that signaling through G protein-coupled receptors of the glucagon superfamily is directly linked to regulation of apoptosis and suggest the existence of a cAMP-dependent protein kinase-, phosphatidylinositol 3-kinase-, and mitogen-activated protein kinase-independent pathway coupling GLP-2R signaling to caspase inhibition and cell survival.

Circulating levels of glucagon-like peptide-2 in human subjects with inflammatory bowel disease.

Glucagon-like peptide-2 (GLP-2) is a recently characterized intestine-derived peptide that exerts trophic activity in the small and large intestine. Whether circulating levels of GLP-2 are perturbed in the setting of human inflammatory bowel disease (IBD) remains unknown. The circulating levels of bioactive GLP-2-(1-33) compared with its degradation product GLP-2-(3-33) were assessed using a combination of RIA and HPLC in normal and immunocompromised control human subjects and patients hospitalized for IBD. The activity of the enzyme dipeptidyl peptidase IV (DP IV), a key determinant of GLP-2-(1-33) degradation was also assessed in the plasma of normal controls and subjects with IBD. The circulating levels of bioactive GLP-2-(1-33) were increased in patients with either ulcerative colitis (UC) or Crohn's Disease (CD; to 229 +/- 65 and 317 +/- 89%, P < 0.05, of normal, respectively). Furthermore, the proportion of total immunoreactivity represented by intact GLP-2-(1-33), compared with GLP-2-(3-33), was increased from 43 +/- 3% in normal healthy controls to 61 +/- 6% (P < 0.01) and 59 +/- 2% (P < 0.01) in patients with UC and CD, respectively. The relative activity of plasma DP IV was significantly reduced in subjects with IBD compared with normal subjects (1.4 +/- 0.3 vs. 5.0 +/- 1.1 mU/ml, respectively; P < 0.05). These results suggest that patients with active IBD may undergo an adaptive response to intestinal injury by increasing the circulating levels of bioactive GLP-2-(1-33), facilitating enhanced repair of the intestinal mucosal epithelium in vivo.

New developments in the biology of the glucagon-like peptides GLP-1 and GLP-2.

Glucagon-like peptides 1 and 2 (GLP-1 and GLP-2) are coencoded within a single mammalian proglucagon precursor, and are liberated in the intestine and brain. GLP-1 exerts well known actions on islet hormone secretion, gastric emptying, and food intake. Recent studies suggest GLP-1 plays a central role in the development and organization of islet cells. GLP-1 receptor signaling appears essential for beta cell signal transduction as exemplified by studies of GLP-1R-/- mice. GLP-2 promotes energy assimilation via trophic effects on the intestinal mucosa of the small and large bowel epithelium via a recently cloned GLP-2 receptor. The actions of GLP-2 are preserved in the setting of small and large bowel injury and inflammation. The biological actions of the glucagon-like peptides suggest they may have therapeutic efficacy in diabetes (GLP-1) or intestinal disorders (GLP-2).

Glucagon-like peptide 2 decreases mortality and reduces the severity of indomethacin-induced murine enteritis.

Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in the gastrointestinal tract. GLP-1 actions regulate blood glucose, whereas GLP-2 exerts trophic effects on intestinal mucosal epithelium. Although GLP-1 actions are preserved in diseases such as diabetes, GLP-2 action has not been extensively studied in the setting of intestinal disease. We have now evaluated the biological effects of a human GLP-2 analog in the setting of experimental murine nonsteroidal antiinflammatory drug-induced enteritis. Human (h)[Gly(2)]GLP-2 significantly improved survival whether administered before, concomitant with, or after indomethacin. h[Gly(2)]GLP-2-treated mice exhibited reduced histological evidence of disease activity, fewer intestinal ulcerations, and decreased myeloperoxidase activity in the small bowel (P < 0.05, h[Gly(2)]GLP-2- vs. saline-treated controls). h[Gly(2)]GLP-2 significantly reduced cytokine induction, bacteremia, and the percentage of positive splenic and hepatic bacterial cultures (P < 0.05). h[Gly(2)]GLP-2 enhanced epithelial proliferation (P < 0.05 for increased crypt cell proliferation in h[Gly(2)]GLP-2- vs. saline-treated mice after indomethacin) and reduced apoptosis in the crypt compartment (P < 0.02). These observations demonstrate that a human GLP-2 analog exerts multiple complementary actions that serve to preserve the integrity of the mucosal epithelium in experimental gastrointestinal injury in vivo.