Safety, feasibility, and short-term outcomes in 588 patients undergoing minimally invasive ileal pouch-anal anastomosis: a single-institution experience.

PURPOSE: A laparoscopic approach to proctocolectomy and ileal pouch-anal anastomosis (IPAA) in patients with chronic ulcerative colitis and familial adenomatous polyposis has grown in popularity secondary to reports of small series demonstrating short-term patient benefits. Limited data exist in large numbers of patients undergoing laparoscopic ileal pouch-anal anastomosis (L-IPAA). We aimed to analyze surgical outcomes in a large cohort of patients undergoing L-IPAA. METHODS: From a prospectively maintained surgical database, 30-day surgical outcome data were reviewed for all L-IPAA performed for chronic ulcerative colitis and familial adenomatous polyposis from 1999 to 2012. Demographics, operative approach, and operative and postoperative complications were analyzed. RESULTS: A total of 588 L-IPAA ileal pouch-anal anastomoses were performed predominantly for chronic ulcerative colitis (93.9 %). The mean age was 36.2 years, and 54.3 % were male, with a mean BMI of 24.1 kg/m(2). Three-stage operations were performed in 17.7 %. The mean operating time of the patients excluding 3-stage operation was 269.4 min. Minimally invasive techniques included hand-assist in 55 % and straight laparoscopy in 45 %. Conversion to open occurred in 8.8 %. Median length of stay was 5 days. There was no mortality. Complications occurred in 36.9 % of patients: Clavien grade I (17.5 %), grade II (72.8 %), and grade III (9.7 %). Analysis of the grouped data over time demonstrated a statistically significant reduction in operative time (p < 0.001) and an increase in the ratio of hand-assisted over straight laparoscopy (p = 0.001). CONCLUSIONS: Minimally invasive IPAA performed using either a laparoscopic or hand-assisted technique is safe, can be performed with low conversion rates, and confers beneficial perioperative outcomes.

Outcomes after implementation of a multimodal standard care pathway for laparoscopic colorectal surgery.

BACKGROUND: The aim of the study was to assess which aspects of an enhanced recovery programme are associated with better outcomes following laparoscopic colorectal surgery. METHODS: A database of laparoscopic colorectal procedures performed in 2011 was reviewed. Elements of the enhanced recovery programme and compliance were evaluated for short-term (30-day) outcomes. Individual elements included gabapentin, celecoxib, intrathecal analgesia, diet, postoperative fluids, and paracetamol/non-steroidal anti-inflammatory drug pain management. RESULTS: Five hundred and forty-one consecutive procedures were included. Compliance with the enhanced recovery programme elements ranged from 82.4 to 99.3 per cent. Median length of hospital stay was 3 (i.q.r. 2-5) days, with 25.9 per cent of patients discharged within 48 h. Patients without complications had a median length of stay of 3 (i.q.r. 2-4) days if compliant and 3 (3-5) days if not (P < 0.001). Low oral opiate intake (oral morphine equivalent of less than 30 mg) (odds ratio (OR) 1.97, 95 per cent confidence interval 1.29 to 3.03; P = 0.002), full compliance (OR 2.36, 1.42 to 3.90; P < 0.001) and high surgeon volume (more than 100 cases per year) (OR 1.50, 1.19 to 1.89; P < 0.001) were associated with discharge within 48 h. Compliance with the elements of oral intake and fluid management in the first 48 h was associated with a reduced rate of complications (8.1 versus 19.6 per cent; P = 0.001). Median oral opiate intake was 37.5 (i.q.r. 0-105) mg in 48 h, with 26.2 per cent of patients receiving no opiates. CONCLUSION: Compliance with an enhanced recovery pathway was associated with less opiate use, fewer complications and a shorter hospital stay.

Case-matched series of enhanced versus standard recovery pathway in minimally invasive colorectal surgery.

BACKGROUND: Accelerated recovery pathways may reduce length of hospital stay after surgery but there are few data on minimally invasive colorectal operations. METHODS: An enhanced recovery pathway (ERP) was instituted, including preoperative analgesia, limited intravenous fluids and opiates, and early feeding. Intrathecal analgesia was administered as needed, but epidural analgesia was not used. The first 66 patients subjected to the ERP were case-matched by surgeon, procedure and age (within 5 years) with patients treated previously in a fast-track pathway (FTP). Short-term and postoperative outcomes to 30 days were compared. RESULTS: Hospital stay was shorter with the ERP than the FTP: median (interquartile range, i.q.r.) 3 (2-3) versus 3 (3-5) days (P < 0·001). A 2-day hospital stay was achieved in 44 and 8 per cent of patients respectively (P < 0·001). Patients in the ERP had a shorter time to recovery of bowel function: median (i.q.r.) 1 (1-2) versus 2 (2-3) days (P < 0·001). Thirty-day complication rates were similar (32 per cent ERP, 27 per cent FTP; P = 0·570). Readmissions within 30 days were more common with ERP, but the difference was not statistically significant (10 versus 5 patients; P = 0·170). Total hospital stay for those readmitted was shorter in the ERP group (18 versus 23 days). CONCLUSION: ERP decreased the length of hospital stay after minimally invasive colorectal surgery.

Outcomes following surgery without radiotherapy for rectal cancer.

BACKGROUND: This study determined survival and recurrence rates following curative resection of rectal cancer without radiotherapy. METHODS: This was a retrospective review of the Mayo Clinic database of patients with rectal cancer treated with curative intent using surgery alone from 1990 to 2006. Patients who received neoadjuvant chemotherapy or radiation therapy and those who had any postoperative radiotherapy were excluded. Details were collected from the database and patient records using a protocol approved by the institutional review board. RESULTS: Some 655 consecutive patients with rectal cancer treated with curative intent using surgery alone were identified; 397 had stage I disease, 125 stage II and 133 stage III. Four hundred and nine patients underwent anterior resection (AR) and 246 abdominoperineal resection (APR). Median follow-up was 62 months. The 5-year rate of local recurrence was 4·3 per cent, disease-free survival 90·0 per cent and cancer-specific survival 91·5 per cent. Stage-specific and all-stage disease-free survival did not differ significantly between AR and APR. The 5-year cumulative local recurrence rate was lower following AR than APR (3·6 versus 5·5 per cent; P = 0·321). There were only two patients with positive margins and type of operation was not significant on multivariable analysis. CONCLUSION: Well-performed, standardized APRs have similar local recurrence to AR. Radiation therapy may not confer much additional benefit.

Endoscopic and surgical management of serrated colonic polyps.

BACKGROUND: Serrated polyps are an inhomogeneous group of lesions that harbour precursors of colorectal cancer. Current research has been directed at further defining the histopathological characteristics of these lesions, but definitive treatment recommendations are unclear. The aim was to review the current literature regarding classification, molecular genetics and natural history of these lesions in order to propose a treatment algorithm for surgeons to consider. METHODS: The PubMed database was searched using the following search terms: serrated polyp, serrated adenoma, hyperplastic polyp, hyperplastic polyposis, adenoma, endoscopy, surgery, guidelines. Papers published between 1980 and 2010 were selected. RESULTS: Sixty papers met the selection criteria. Most authors agree that recommendations regarding endoscopic or surgical management should be based on the polyp's neoplastic potential. Polyps greater than 5 mm should be biopsied to determine their histology so that intervention can be directed accurately. Narrow-band imaging or chromoendoscopy may facilitate the detection and assessment of extent of lesions. Complete endoscopic removal of sessile serrated adenomas in the left or right colon is recommended. Follow-up colonoscopy is recommended in 2-6 months if endoscopic removal is incomplete. If the lesion cannot be entirely removed endoscopically, segmental colectomy is strongly recommended owing to the malignant potential of these polyps. Left-sided lesions are more likely to be pedunculated, making them more amenable to successful endoscopic removal. CONCLUSION: Even though the neoplastic potential of certain subtypes of serrated polyp is heavily supported, further studies are needed to make definitive endoscopic and surgical recommendations.

Immunoreactivity for Ano1 detects depletion of Kit-positive interstitial cells of Cajal in patients with slow transit constipation.

BACKGROUND: Depletion of interstitial cells of Cajal (ICC) is associated with several gastrointestinal (GI) motility disorders. Changes in ICC networks are usually detected by immunolabeling for the receptor tyrosine kinase Kit. Ano1 (DOG1 or TMEM16A) was recently described as a marker of ICC in GI tract. Our aim was to determine whether Ano1 immunoreactivity can be used as a reliable marker for ICC in tissues from patients with motility disorders. METHODS: Four tissues from patients with normal ICC numbers and four tissues from patients with slow transit constipation and loss of Kit-positive ICC were studied. Interstitial cells of Cajal were detected by double labeling using antisera to Kit and Ano1. KEY RESULTS: Both the processes and cell bodies of ICC in tissue from controls and slow transit constipation were immunoreactive for Ano1. There was a near complete overlap between Kit and Ano1 immunoreactivity. Tissues from patients with slow transit constipation contained significantly fewer Ano1-positive ICC than control tissues. The numbers of ICC identified by Ano1 and Kit immunoreactivity were nearly identical across the range of ICC numbers from an average of 1.64 to 7.05 cells per field and correlated with an R(2) value of 0.99. CONCLUSIONS & INFERENCES: Ano1 is a reliable and sensitive marker for detecting changes in ICC networks in humans. Labeling with antibodies selective for Ano1 reproducibly detects depletion of Kit-positive ICC in tissues from patients with slow transit constipation.

Short-term outcomes after elective minimally invasive colectomy for diverticulitis.

BACKGROUND: The role of minimally invasive surgery in complicated diverticulitis is still being elucidated. The aim of this study was to compare short-term outcomes in patients undergoing minimally invasive surgery for complicated or uncomplicated diverticular disease. METHODS: All patients who had elective minimally invasive surgery for diverticulitis between 2003 and 2008 were identified from a prospectively maintained database. Complicated disease was defined as diverticulitis associated with abscess, fistula, stricture or bleeding. Univariable analysis was performed to compare safety and short-term outcomes in patients with complicated and uncomplicated diverticulitis. RESULTS: A total of 361 patients (136 with complicated and 225 with uncomplicated diverticulitis) were operated on with either a laparoscopic (36·0 per cent) or a hand-assisted laparoscopic (64·0 per cent) surgical technique. There were no significant differences between the groups with respect to age, sex, body mass index, laparoscopic approach, postoperative recovery protocol or previous open surgery. Conversion rates were similar for complicated and uncomplicated disease (14·0 versus 11·6 per cent respectively; P = 0·514). There was no difference between the groups with respect to return of bowel function (mean 3·1 versus 3·2 days respectively; P = 0·156), morbidity (27·9 versus 19·6 per cent; P = 0·070) or mean length of stay (5·4 versus 4·8 days; P = 0·186). There were no deaths within 30 days. CONCLUSION: Elective minimally invasive colectomy is feasible for patients with uncomplicated and complicated diverticulitis, with equivalent outcomes.

Changes in interstitial cells of cajal with age in the human stomach and colon.

BACKGROUND: Aging produces inevitable changes in the function of most organs including the gastrointestinal tract. Together with enteric nerves and smooth muscle cells, interstitial cells of Cajal (ICC) play a key role in the control of gastrointestinal motility, yet little is known about the effect of aging on ICC. The aim of this study was to determine the effect of aging on ICC number and volume in the human stomach and colon. METHODS: Gastric and colonic tissues from patients aged 25-70 and 36-92 years old, respectively, and with no co-existent motility disorders were immunolabeled with an anti-Kit antibody and ICC were counted in the circular muscle and myenteric regions. Network volumes were measured using 3D reconstructions of confocal stacks. The effects of aging were determined by testing for linear trends using regression analysis. KEY RESULTS: In both stomach and colon, the number of ICC bodies and volume significantly decreased with age at a rate of 13% per decade. ICC size was only affected in the myenteric plexus in the colon. The changes associated with age were not differentially affected by sex or colonic region. CONCLUSIONS & INFERENCES: The number and volume of ICC networks in the normal human stomach and colon decline with age. This decrease in ICC likely reduces the functional capacity of the gastrointestinal motor apparatus, may contribute to changes in gastrointestinal motility with aging and may influence intestinal responses to insults such as disease, operative interventions and medications in older patients. Tissue specimens must be carefully age-matched when studying ICC in disease.

Quality of life after coloanal anastomosis and abdominoperineal resection for distal rectal cancers: sphincter preservation vs quality of life.

AIM: A permanent colostomy is considered to have an adverse impact on quality of life (QOL). However, functional outcomes following sphincter preservation also affect QOL. Our aim was to determine differences in QOL of patients undergoing coloanal anastomosis (CAA) or abdominoperineal resection (APR) for distal rectal cancer. METHOD: Eighty-five patients underwent CAA (72 with intestinal continuity and 13 with a stoma because of complications) and 83 patients underwent APR for a distal rectal cancer between 1995 and 2001 at a single institution and responded to our survey. QOL was evaluated using the EORTC QLQ-C30 and QLQ-CR38. RESULTS: Patients with CAA were younger than APR patients (mean age 57 vs 62 years, P < 0.001), but gender distribution, tumour stage and proportion of subjects receiving radiotherapy was not significantly different. Patients undergoing CAA had higher scores (better QOL) for physical functioning; lower scores (fewer symptoms) for fatigue, pain, financial difficulties, weight loss and chemotherapy side effects; and higher scores (more symptoms) for constipation and gastrointestinal symptoms compared with APR patients. CAA patients had higher scores (better QOL) for body image in men but not in women. Sexual functioning scores in men and women were lower (worse QOL) in CAA patients compared with APR patients. CONCLUSIONS: QOL after APR is comparable to sphincter preservation, although there are some differences that need to be considered. QOL and functional results should be taken into account with the oncological outcome when devising management strategy for distal rectal cancer.

Laparoscopic surgery for rectal cancer: short-term benefits and oncologic outcomes using more than one technique.

BACKGROUND: Several minimally invasive techniques have now been described for rectal cancer resection. Current outcome data for these approaches from high volume, single institutions remain limited. Our aim was to review outcomes in patients undergoing minimally invasive surgery for rectal cancer at our institution in the current era. METHODS: A retrospective analysis was done to assess short-term benefits and oncologic outcomes in patients undergoing minimally invasive surgery for rectal cancer between 2004 and 2007. RESULTS: One-hundred consecutive patients (61 men, median age 62) with a median follow-up of 1.8 years were identified. Sixty-seven had hand-assisted laparoscopic surgery (HALS), while 33 were done laparoscopic-assisted (LA). Seventy-two patients underwent anterior resection, 27 an abdominal perineal resection, and 1 a total proctocolectomy. Tumor stage was stage 1 (21%), stage 2 (17%), stage 3 (56%), and stage 4 (6%). A median of 16 lymph nodes, a median 3.4 cm distal margin, and a 99% negative circumferential margin was achieved. The 3-year disease-free and overall survivals were 86.2 and 94.5%, respectively. Three cases required conversion. Median time to both diet and first bowel movement was 3 days, and median length of stay was 5 days. Length of stay, time to soft diet, incision length, and pain scores were less using a LA approach compared to HALS (P < 0.01). Overall morbidity was 26% with no mortality. CONCLUSION: Both minimally invasive techniques used achieved excellent oncologic results in patients with rectal cancer. The LA approach had slightly better short-term outcomes.

Effect of age on the enteric nervous system of the human colon.

The effect of age on the anatomy and function of the human colon is incompletely understood. The prevalence of disorders in adults such as constipation increase with age but it is unclear if this is due to confounding factors or age-related structural defects. The aim of this study was to determine number and subtypes of enteric neurons and neuronal volumes in the human colon of different ages. Normal colon (descending and sigmoid) from 16 patients (nine male) was studied; ages 33-99. Antibodies to HuC/D, choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and protein gene product 9.5 were used. Effect of age was determined by testing for linear trends using regression analysis. In the myenteric plexus, number of Hu-positive neurons declined with age (slope = -1.3 neurons/mm/10 years, P = 0.03). The number of ChAT-positive neurons also declined with age (slope = -1.1 neurons/mm/10 years of age, P = 0.02). The number of nNOS-positive neurons did not decline with age. As a result, the ratio of nNOS to Hu increased (slope = 0.03 per 10 years of age, P = 0.01). In the submucosal plexus, the number of neurons did not decline with age (slope = -0.3 neurons/mm/10 years, P = 0.09). Volume of nerve fibres in the circular muscle and volume of neuronal structures in the myenteric plexus did not change with age. In conclusion, the number of neurons in the human colon declines with age with sparing of nNOS-positive neurons. This change was not accompanied by changes in total volume of neuronal structures suggesting compensatory changes in the remaining neurons.

Transvaginal colonic extraction following combined hysterectomy and laparoscopic total colectomy: a natural orifice approach.

A major advantage of laparoscopic colectomy is the limited incision. We describe an innovative technique in which the entire colon is extracted transvaginally to avoid any abdominal extraction incision in a female patient with hereditary nonpolyposis colon cancer who required total colectomy and hysterectomy. This novel technical approach is feasible and safe, eliminates the need for any extraction abdominal incision, and may be considered in patients requiring concurrent abdominal colectomy and hysterectomy.

Ileal pouch-anal anastomosis and liver transplantation for ulcerative colitis complicated by primary sclerosing cholangitis.

BACKGROUND: The aim was to evaluate outcomes in patients with ulcerative colitis complicated by primary sclerosing cholangitis (PSC) who required ileal pouch-anal anastomosis (IPAA) and orthotopic liver transplantation (OLT). METHODS: A retrospective analysis was performed of 32 patients undergoing both IPAA and OLT between 1980 and 2006. Data were collected regarding demographics, indication for surgery, postoperative complications, and outcome of IPAA and OLT. RESULTS: Thirty-day mortality after either procedure was nil. The median preoperative Model for End-stage Liver Disease (MELD) score for the group with initial IPAA was 8 (range 6-20) and the postoperative score was 11 (range 6-19). At 1 and 10 years, 32 and 26 of the 32 liver grafts had survived, and 31 and 30 of the 32 pouches, respectively. Fourteen patients require daily medical therapy for chronic pouchitis. At a median follow-up of 3.6 (range 0.2-16.2) years after the second of two procedures, responding patients reported a median of 5.5 stools per day and 2 stools per night. CONCLUSION: IPAA and OLT are feasible and safe in patients requiring both procedures for ulcerative colitis and PSC. Functional outcomes are stable over time, despite an increased risk of chronic pouchitis.

New developments in diverticular disease.

Colonic diverticular disease is common but surprisingly poorly understood. Recent advances in the field continue to focus on the introduction of new technology. Diagnosis and assessment of the severity of acute diverticulitis is improved with CT scanning. A specialized bleeding team employing advanced endoscopic techniques can control diverticular bleeding so that emergency surgical resection may be avoided. Selected patients undergoing laparoscopic sigmoid resection may benefit from this approach. The vast majority of reports are from retrospective studies and include few randomized, controlled trials.

Luminal osmolarity downregulates gene expression of Na+/H+ exchanger (NHE3) in rat colon mucosa.

Water-coupled Na&sup+ absorption in the colon is mediated principally by Na+/H+ exchange (isoforms NHE2 and NHE3). To determine whether luminal ion composition or osmolarity influences NHE expression in colon mucosa, two groups (n = 6 in each) of adult male Sprague-Dawley rats underwent sham laparotomy or loop ileostomy. In these studies, diversion did not markedly alter mRNA levels for NHE2, NHE3, or Na+/K+, at 8 or 21 days, indicating that loss of luminal volume does not alter NHE gene expression. To evaluate the effects of specific luminal components, we infused equal volumes of half-normal (154 mOsm) or iso-osmolar (308 mOsm) solutions of saline and mannitol into the diverted colon. All solutions elicited significant (45% to 60%; P <0.05) decreases in mRNA levels for NHE3, with iso-osmolar mannitol eliciting the greatest changes. Decreases in NHE2 and Na+/K+ mRNA levels were observed following these infusions but were not as marked as the changes for NHE3. These findings suggest that (1) loss of luminal Na+ is not, in itself, a signal that regulates NHE expression and (2) infusion of any solute, including Na+ itself, provides a signal to downregulate expression of NHE3 in colon mucosa.

Selective decreases in levels of mRNA encoding a water channel (AQP3) in ileal mucosa after ileostomy in the rat.

Water channels (aquaporins) provide pathways for water permeation in a variety of epithelia. Aquaporin-3 (AQP3) has been localized to the basolateral membranes of epithelial cells in the small intestine, but mechanisms that regulate its expression and function have not been explored. To determine whether luminal content may influence intestinal AQP3 gene expression, adult Sprague-Dawley rats underwent sham laparotomy (N = 11) or loop ileostomy (N = 9) and were killed 8 days after procedures. Northern blot analysis was used to measure messenger RNA (mRNA) levels for AQP3 and the Na(+)/K(+) ATPase, a housekeeping transporter that regulates cellular levels of Na(+) and K(+). At sacrifice, histologic examination revealed only minimal changes in mucosal morphology. In sham animals, Na/K mRNA levels increased moderately in distal regions of the small intestine. Ileostomy did not alter these levels in any region. In contrast, in sham animals, AQP3 mRNA levels increased along the length of the intestine and were markedly higher in the distal ileum. Diversion of luminal contents decreased AQP3 mRNA levels in the postileostomy region by 30% to 50%. These findings indicate regional variations in expression of the AQP3 water channel in mucosa of the small intestine. In addition, they suggest that AQP3 gene expression may depend on the presence of luminal contents.

Expression of an extracellular calcium-sensing receptor in rat stomach.

BACKGROUND & AIMS: Circulating levels of Ca2+ can influence secretory functions and myoelectrical properties of the stomach. A Ca2+-sensing receptor (CaR) has recently been identified in tissues that regulate systemic Ca2+ homeostasis. The aim of this study was to evaluate expression of CaR in the stomach of the rat. METHODS: In forestomach and glandular stomach, reverse-transcription polymerase chain reaction was used to amplify a 380-base pair product, which is 99% homologous with transcripts obtained in parathyroid and kidney. RESULTS: Northern analysis of gastric mucosal polyA+ RNA revealed 7. 5- and 4.1-kilobase transcripts, similar to those obtained in rat parathyroid and kidney. Immunohistochemistry revealed CaR expression in regions of the submucosal plexus and myenteric neurons. In sections of intact tissue, preparations of primary culture surface cells and surgically dissected gastric glands, staining was observed consistently in epithelial cells of the gastric glands and in gastric surface cells. In parietal cells in isolated gastric glands, intracellular levels of Ca2+ responded to conditions that are known to activate CaR. CONCLUSIONS: These are the first reported observations that CaR is expressed in different epithelial cells of mammalian gastric mucosa and its enteric nerve regions. The effects of extracellular Ca2+ on gastric function may be attributable to activation of CaR.

Selective increase in gastric mucosal mRNA encoding basolateral Na-K-2C1 cotransporter following ileostomy in the rat.

Results of previous studies suggest that major surgical resections or reconstructions of the distal small intestine can alter morphologic and functional properties of the stomach. Little is known about the effect of lesser surgical alterations such as construction of an ileostomy, on the morphology and transport properties of the gastric mucosa. To evaluate the effects of ileostomy, Sprague-Dawley rats underwent sham laparotomy (n = 10) or loop ileostomy construction (n = 10). After body weights had stabilized ( approximately 21 days) the animals were killed. Gastric mucosal scrapings were prepared for Northern blot analysis of messenger RNA levels for (1) H/K ATPase, found in parietal cells; (2) Na-K-2C1 cotransporter, found in both parietal and surface cells; and (3)Na/K ATPase, found in all gastric mucosal cells. Gastric mucosa from ileostomy animals was visibly hypertrophied compared to sham-operated animals. There was a 145% increase in the mRNA levels of the Na-K-2Cl cotransporter in gastric mucosa of the ileostomy group but no significant changes in H/K ATPase or Na/K ATPase mRNA levels. Construction of an ileostomy selectively enhances expression of the Na-K-C1 cotransporter in the gastric mucosa. Further studies are required to understand the neurohumoral stimuli underlying this selective response.