Patient-Reported Bowel, Urinary, and Sexual Outcomes After Laparoscopic-Assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial (ALaCart).

OBJECTIVE: The aim of this study was to compare patient-reported urinary, bowel, and sexual functioning of ALaCaRT Trial participants randomized to open or laparoscopic surgery for rectal cancer. SUMMARY BACKGROUND DATA: The primary endpoint, noninferiority of laparoscopic surgical resection adequacy, was not established. METHODS: Participants completed QLQ-CR29 at baseline, 3, and 12 months post-surgery. Additionally, women completed Rosen's Female Sexual Functioning Index (FSFI). Men completed the International Index of Erectile Function (IIEF) and QLQ-PR25. We compared the proportions of participants in each group who experienced moderate/severe symptoms/dysfunction at each time-point and compared mean difference scores from baseline to 12 months between groups. All analyses were intention-to-treat. Sexual functioning analyses included only the participants who expressed sexual interest at baseline. RESULTS: Baseline PRO compliance of 475 randomized participants was 88%. At 12 months, a lower proportion of open surgery participants experienced moderate-severe fecal incontinence and sore skin, compared to Laparoscopic participants, and a lower proportion of men randomized to open surgery experienced moderate-severe urinary symptoms. There were no differences at 3 months for bowel or urinary symptoms. Sexual functioning among sexually interested participants was similar between groups at 3 and 12 months; however, a lower proportion of women reported moderate to severe sexual dissatisfaction at 3 months in the open as compared to the laparoscopic group, (Rebecca.mercieca@sydney.edu.au., 95% CI 0.03-0.39). DISCUSSION: Despite the slightly lower proportions of open surgery participants self-reporting moderate-severe symptoms for 3 of 16 urinary/bowel domains, and lack of differences in sexual domains, it remains difficult to recommend one surgical approach over another for rectal resection.

Functional Outcome of Laparoscopic-Assisted Resection Versus Open Resection of Rectal Cancer: A Secondary Analysis of the Australasian Laparoscopic Cancer of the Rectum Trial.

BACKGROUND: Low anterior resection syndrome has a significant impact on the quality of life in rectal cancer survivors. Previous studies comparing laparoscopic to open rectal resection have neglected bowel function outcomes. OBJECTIVE: This study aimed to assess whether there is a difference in the functional outcome between patients undergoing laparoscopic versus open resection for rectal adenocarcinoma. DESIGN: Cross-sectional prevalence of low anterior resection syndrome was assessed in a secondary analysis of the multicenter phase 3 randomized clinical trial, Australasian Laparoscopic Cancer of the Rectum Trial (ACTRN12609000663257). SETTING: There were 7 study subsites across New Zealand and Australia. PATIENTS: Participants were adults with rectal cancer who underwent anterior resection and had bowel continuity. MAIN OUTCOME MEASURES: Postoperative bowel function was evaluated using the validated low anterior resection syndrome score and Bowel Function Instrument. RESULTS: The Australasian Laparoscopic Cancer of the Rectum Trial randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. A total of 257 participants were eligible for, and invited to, participate in additional follow-up; 163 (63%) completed functional follow-up. Overall cross-sectional prevalence of major low anterior resection syndrome was 49% (minor low anterior resection syndrome 27%). There were no differences in median overall Bowel Function Instrument score nor low anterior resection syndrome score between participants undergoing laparoscopic versus open surgery (66 vs 67, p = 0.52; 31 vs 27, p = 0.24) at a median follow-up of 69 months. LIMITATIONS: The major limitations are a result of conducting a secondary analysis; the likelihood of an insufficient sample size to detect a difference in prevalence between the groups and the possibility of selection bias as a subset of the randomized population was analyzed. CONCLUSIONS: Bowel dysfunction affects a majority of rectal cancer patients for a significant time after the operation. In this secondary analysis of a randomized trial, surgical approach does not appear to influence the likelihood or severity of low anterior resection syndrome. See Video Abstract at http://links.lww.com/DCR/B794. RESULTADO FUNCIONAL DE LA RESECCIN ASISTIDA POR LAPAROSCOPIA VERSUS RESECCIN ABIERTA EN CNCER DE RECTO ANLISIS SECUNDARIO DEL ESTUDIO DE CNCER DE RECTO LAPAROSCPICO DE AUSTRALASIA: ANTECEDENTES:El síndrome de resección anterior baja tiene un impacto significativo en la calidad de vida de los supervivientes de cáncer de recto. Los estudios anteriores que compararon la resección rectal laparoscópica con la abierta no han presentado resultados de la función intestinal.OBJETIVO:Evaluar si existe una diferencia en el resultado funcional entre los pacientes sometidos a resección laparoscópica versus resección abierta por adenocarcinoma de recto.DISEÑO:La prevalencia transversal del síndrome de resección anterior baja se evaluó en un análisis secundario del ensayo clínico aleatorizado multicéntrico de fase 3, Estudio Sobre el Cáncer de Recto Laparoscópico de Australasia (Australasian Laparoscopic Cancer of the Rectum Trial, ACTRN12609000663257).AJUSTE:Siete subsitios de estudio en Nueva Zelanda y Australia.PACIENTES:Los participantes eran adultos con cáncer de recto que se sometieron a resección anterior con anastomosis.PRINCIPALES MEDIDAS DE RESULTADO:La función intestinal posoperatoria se evaluó utilizando el previamente validado puntaje LARS y el Instrumento de Función Intestinal.RESULTADOS:El Estudio Sobre el Cáncer de Recto Laparoscópico de Australasia asignó al azar a 475 pacientes con adenocarcinoma rectal T1-T3 a menos de 15 cm del borde anal. 257 participantes fueron elegibles e invitados a participar en un seguimiento adicional. 163 (63%) completaron el seguimiento funcional. La prevalencia transversal general de LARS mayor fue del 49% (LARS menor 27%). No hubo diferencias en la puntuación media general del Instrumento de Función Intestinal ni en la puntuación LARS entre los participantes sometidos a cirugía laparoscópica versus cirugía abierta (66 frente a 67, p = 0,52; 31 frente a 27, p = 0,24) en una mediana de seguimiento de 69 meses.LIMITACIONES:Las principales limitaciones son el resultado de realizar un análisis secundario; se analizó la probabilidad de un tamaño de muestra insuficiente para detectar una diferencia en la prevalencia entre los grupos y la posibilidad de sesgo de selección como un subconjunto de la población aleatorizada.CONCLUSIONES:La disfunción intestinal afecta a la mayoría de los pacientes con cáncer de recto durante un tiempo significativo después de la operación. En este análisis secundario de un ensayo aleatorizado, el abordaje quirúrgico no parece influir en la probabilidad o gravedad del síndrome de resección anterior baja. Consulte Video Resumen en http://links.lww.com/DCR/B794. (Traducción-Dr. Felipe Bellolio).

Disease-free Survival and Local Recurrence After Laparoscopic-assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to determine the efficacy of laparoscopic rectal resection (Lap) versus open laparotomy and rectal resection (Open) for rectal cancer on locoregional recurrence (LRR) and disease-free survival (DFS) at 2 years. SUMMARY BACKGROUND DATA: Although a Lap approach to colon cancer surgery may offer similar oncological outcomes to Open with potentially less morbidity, this remains to be clearly established for the treatment of rectal cancer. METHODS: A randomized, multicenter noninferiority phase 3 trial of 475 patients with T1 to T3 rectal adenocarcinoma <15 cm from anal verge, given Lap or Open and followed for a minimum 2 years to assess LRR, DFS, and overall survival (OS). RESULTS: Secondary endpoint analyses included 450 patients (95%) without metastases at baseline (mean age 64; 34% women) who received Lap (n = 225) or Open (n = 225). Median follow-up was 3.2 years (range: 0.1-5.4 yrs). LRR cumulative incidence at 2 years: Lap 5.4%; Open 3.1% [difference, 2.3%; 95% confidence interval (CI), -1.5% to 6.1%; hazard ratio (HR) 1.7; 95% CI, 0.74-3.9]. DFS at 2 years: Lap 80%; Open 82% (difference, 2.0%; 95% CI, -9.3% to 5.4%; HR for recurrence or death, 1.17; 95% CI, 0.81-1.68; P = 0.41). After adjustment for baseline factors HR = 1.07 (95% CI, 0.7-1.6). OS at 2 years: Lap 94%; Open 93% (difference 0.9%; 95% CI, -3.6% to 5.4%). CONCLUSIONS: Laparoscopic surgery for rectal cancer did not differ significantly from open surgery in effects on 2-year recurrence or DFS and OS. Confidence intervals included potentially clinically important differences favoring open resection, so that the combination of primary and secondary study endpoints may not support laparoscopic resection of rectal cancer as a routine standard of care and further follow-up is required.

Management of Low Colorectal Anastomotic Leakage in the Laparoscopic Era: More Than a Decade of Experience.

BACKGROUND: Anastomotic leak after colorectal surgery increases postoperative mortality, cancer recurrence, permanent stoma formation, and poor bowel function. Anastomosis between the colon and rectum is a particularly high risk. Traditional management mandates laparotomy, disassembly of the anastomosis, and formation of an often-permanent stoma. After laparoscopic colorectal surgery it may be possible to manage anastomotic failure with laparoscopy, thus avoiding laparotomy. OBJECTIVE: The purpose of this study was to determine the feasibility of the laparoscopic management of failed low colorectal anastomoses. SETTING: This was a single-institute case series. PATIENTS: A total of 555 laparoscopic patients undergoing anterior resection with primary anastomosis within 10 cm of the anus in the period 2000-2012 were included. MAIN OUTCOME MEASURES: Anastomotic failure, defined as any clinical or radiological demonstrable defect in the anastomosis; complications using the Clavien-Dindo system; mortality within 30 days; and patient demographics and risk factors, as defined by the Charlson index, were measured. RESULTS: Leakage occurred in 44 (7.9%) of 555 patients, 16 patients with a diverting ileostomy and 28 with no diverting ileostomy. Leakage was more common in those with anastomoses <5 cm form the anus, male patients, and those with a colonic J-pouch and rectal cancer. Diverting ileostomy was not protective of anastomotic leakage. In those patients with anastomotic leakage and a primary diverting ileostomy, recourse to the peritoneal cavity was required in 4 of 16 patients versus 24 of 28 without a diverting ileostomy (p = 0.0002). In 74% of those cases, access to the peritoneal cavity was achieved through laparoscopy. Permanent stoma rates were very low, including 14 (2.5%) of 555 total patients or 8 (18.0%) of 44 patients with anastomotic leakage. Thirty-day mortality was rare (0.6%). LIMITATIONS: This study was limited by the lack of a cohort of open cases for comparison. CONCLUSIONS: Laparoscopic anterior resection is associated with low levels of complications, including anastomotic leak, postoperative mortality, and permanent stoma formation. Anastomotic leakage can be managed with laparoscopy in the majority of cases. See Video Abstract at http://links.lww.com/DCR/A353.

Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial.

IMPORTANCE: Laparoscopic procedures are generally thought to have better outcomes than open procedures. Because of anatomical constraints, laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection. OBJECTIVE: To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance. DESIGN, SETTING, AND PARTICIPANTS: Randomized, noninferiority, phase 3 trial (Australasian Laparoscopic Cancer of the Rectum; ALaCaRT) conducted between March 2010 and November 2014. Twenty-six accredited surgeons from 24 sites in Australia and New Zealand randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. INTERVENTIONS: Open laparotomy and rectal resection (n = 237) or laparoscopic rectal resection (n = 238). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of oncological factors indicating an adequate surgical resection, with a noninferiority boundary of Δ = -8%. Successful resection was defined as meeting all the following criteria: (1) complete total mesorectal excision, (2) a clear circumferential margin (≥1 mm), and (3) a clear distal resection margin (≥1 mm). Pathologists used standardized reporting and were blinded to the method of surgery. RESULTS: A successful resection was achieved in 194 patients (82%) in the laparoscopic surgery group and 208 patients (89%) in the open surgery group (risk difference of -7.0% [95% CI, -12.4% to ∞]; P = .38 for noninferiority). The circumferential resection margin was clear in 222 patients (93%) in the laparoscopic surgery group and in 228 patients (97%) in the open surgery group (risk difference of -3.7% [95% CI, -7.6% to 0.1%]; P = .06), the distal margin was clear in 236 patients (99%) in the laparoscopic surgery group and in 234 patients (99%) in the open surgery group (risk difference of -0.4% [95% CI, -1.8% to 1.0%]; P = .67), and total mesorectal excision was complete in 206 patients (87%) in the laparoscopic surgery group and 216 patients (92%) in the open surgery group (risk difference of -5.4% [95% CI, -10.9% to 0.2%]; P = .06). The conversion rate from laparoscopic to open surgery was 9%. CONCLUSIONS AND RELEVANCE: Among patients with T1-T3 rectal tumors, noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established. Although the overall quality of surgery was high, these findings do not provide sufficient evidence for the routine use of laparoscopic surgery. Longer follow-up of recurrence and survival is currently being acquired. TRIAL REGISTRATION: anzctr.org Identifier: ACTRN12609000663257.

Cost savings for elective laparoscopic resection compared with open resection for colorectal cancer in a region of high uptake.

BACKGROUND: Previous cost analyses of laparoscopic resection for colorectal cancer (CRC) reported slightly higher or similar costs to those of open resection. These analyses were based on randomised controlled trials when the laparoscopic approach was newly adopted. This study compared costs for laparoscopic versus open resection in a region of high uptake where adoption is mature. METHODS: Hospital cost data were obtained for elective resections for CRC that occurred between June 2009 and June 2011 in public hospitals in Queensland, Australia. The primary outcome was total cost and secondary outcomes were length-of-stay, operating time, and ICU admission. Multivariate least-squares regression was used to adjust for potential confounders: age, sex, comorbidities, procedure, and hospital volume. RESULTS: The crude mean cost for laparoscopic resection was euro 20,036 compared with that for open resection of euro 22,780 (difference = euro 2,744). Patients who underwent laparoscopic resection (744/1,397; 53 %) were slightly younger and had fewer comorbidities (decreasing costs) but more had rectal surgery (increasing costs). The adjusted mean cost for laparoscopic resection was euro 20,396 compared with euro 22,442 for open resection (difference = euro 2,054). Compared with open resection, when adjusted for potential confounders, laparoscopic resection resulted in similar operating time (216 vs. 214 min), shorter length-of-stay (difference = -1.1 days, 95 % CI -1.9, -0.3), and shorter admission to ICU (difference = -7.3 h, 95 % CI -11.9, -2.7). CONCLUSIONS: This non-randomised study in a region of high uptake found a similar operating time and lower cost for laparoscopic resection for CRC compared with those of open resection due to a shorter length-of-stay and shorter time in ICU. Laparoscopic resection for CRC saves money when the procedure is widely adopted and surgeons are experienced in the technique.

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration.

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

Cellular settings mediating Src Substrate switching between focal adhesion kinase tyrosine 861 and CUB-domain-containing protein 1 (CDCP1) tyrosine 734.

Reciprocal interactions between Src family kinases (SFKs) and focal adhesion kinase (FAK) are critical during changes in cell attachment. Recently it has been recognized that another SFK substrate, CUB-domain-containing protein 1 (CDCP1), is differentially phosphorylated during these events. However, the molecular processes underlying SFK-mediated phosphorylation of CDCP1 are poorly understood. Here we identify a novel mechanism in which FAK tyrosine 861 and CDCP1-Tyr-734 compete as SFK substrates and demonstrate cellular settings in which SFKs switch between these sites. Our results show that stable CDCP1 expression induces robust SFK-mediated phosphorylation of CDCP1-Tyr-734 with concomitant loss of p-FAK-Tyr-861 in adherent HeLa cells. SFK substrate switching in these cells is dependent on the level of expression of CDCP1 and is also dependent on CDCP1-Tyr-734 but is independent of CDCP1-Tyr-743 and -Tyr-762. In HeLa CDCP1 cells, engagement of SFKs with CDCP1 is accompanied by an increase in phosphorylation of Src-Tyr-416 and a change in cell morphology to a fibroblastic appearance dependent on CDCP1-Tyr-734. SFK switching between FAK-Tyr-861 and CDCP1-Tyr-734 also occurs during changes in adhesion of colorectal cancer cell lines endogenously expressing these two proteins. Consistently, increased p-FAK-Tyr-861 levels and a more epithelial morphology are seen in colon cancer SW480 cells silenced for CDCP1. Unlike protein kinase Cδ, FAK does not appear to form a trimeric complex with Src and CDCP1. These data demonstrate novel aspects of the dynamics of SFK-mediated cell signaling that may be relevant during cancer progression.

Prolonged use of thromboprophylaxis may not be necessary in laparoscopic colorectal surgery.

PURPOSE: Patients undergoing colorectal resections are considered high risk for developing thromboembolic disease. We postulate, however, that the rapid recovery and swift mobilization after laparoscopic resections reduce this risk and that these patients therefore do not need prolonged thromboprophylaxis. This hypothesis was tested in this paper. METHODS: All patients who underwent laparoscopic colorectal surgery in our Colorectal Surgical Unit in the period from June 1991 until January 2010 were entered into a prospective database. The entire database was reviewed, and incidence of thromboembolic disease and significant bleeding complications were noted. RESULTS: Three thousand, three hundred sixty-four patients were laparoscopically operated on for colorectal disease and were entered in the database. Two thousand, one hundred twenty-seven patients were operated on for benign disease; 1,230, for colorectal cancer, and four, for other malignancies. Two deep venous thromboses were encountered (0.059%), and ten patients had pulmonary embolism (0.30%). The combined venous thromboembolism (VTE) risk for the overall group of patients undergoing laparoscopic colorectal operations is 0.36%. The combined VTE risk was 0.57% (7/1,230) in patients with colorectal cancer and 0.24% (5/2,127) in patients with benign disease (p = 0.118). Bleeding complications occurred in 44 patients (1.3%). CONCLUSIONS: In our group, the combined VTE risk for the overall group of patients undergoing laparoscopic colorectal operations is 0.36%. Therefore, we postulate that the prolonged use of thromboprophylaxis is not indicated in the vast majority of patients undergoing laparoscopic colorectal surgery. In particular, patients undergoing laparoscopic resections for benign disease and without other risk factors have such a low VTE risk that prolonged prophylaxis is probably not warranted.

National trends in the uptake of laparoscopic resection for colorectal cancer, 2000-2008.

OBJECTIVE: To examine the trends in the uptake of laparoscopic resection for colorectal cancer. DESIGN AND SETTING: Retrospective analysis of Australia-wide data on elective resections for colorectal cancer over the 8 financial years 2000-01 to 2007-08, obtained from the National Hospital Morbidity Database. MAIN OUTCOME MEASURES: National trends in annual percentage of colorectal resections for cancer that were conducted laparoscopically for each year, stratified by hospitals conducting a high volume of elective resections (40 or more/year) versus a low volume, and by public versus private hospitals. RESULTS: For all Australian hospitals combined, the percentage of resections for colon cancer conducted laparoscopically increased from 2.4% in 2000-01 to 27.5% in 2007-08. For rectal cancer, this increase was from 1.1% to 21.5%. The largest increases were seen in high-volume private hospitals (colon cancer, 2.7% to 34.1%; rectal cancer, 1.5% to 26.2%), but increases also occurred in high-volume public hospitals (colon cancer, 2.7% to 32.2%; rectal cancer, 0.5% to 20.3%), low-volume private (colon cancer, 3.8% to 27.1%; rectal cancer, 2.4% to 25.5%) and low-volume public (colon cancer, 1.1% to 17.0%; rectal cancer, 0.5% to 13.8%) hospitals. CONCLUSIONS: The use of laparoscopic resection for colorectal cancer has increased throughout Australian hospitals. Our findings provide the data necessary to ensure adequate resource allocation by the appropriate medical bodies to achieve optimal success in the uptake of laparoscopic resection for colorectal cancer in Australia.

The effect of obstruction and perforation on colorectal cancer disease-free survival.

BACKGROUND: Obstruction (OBSTR) and perforation (PERF) in colorectal cancer impact adversely upon outcomes, and cancer-related survival may also be affected. However, data are sparse, particularly on disease-free survival (DFS) where the cancer is both obstructed and perforated (OBS-PERF). METHODS: Data were extracted from a prospectively collected database of 1876 colorectal cancer patients managed and followed up at the Royal Brisbane Hospital from 1984 to 2004. The patients who had curative surgery (n = 1426) were classified as OBSTR (n = 153), PERF (n = 53), OBS-PERF (n = 19), and uncomplicated (UNCOM; n = 1201). Kaplan-Meier survival and Cox proportional hazard analyses were performed. RESULTS: Postoperative mortality within 30 days of surgery was 1.5% (n = 22) and the overall complication rate was 40.8% (n = 582). However, only 7.2% (n = 102) required reoperations. The median survival time was 71 (IQR = 64.9-77.1) months and the median follow-up for DFS was 37.5 (IQR 14-68) months. The overall recurrence rate was 32.7% (n = 466), the local recurrence rate was 9.4% (n = 135), and local and distant recurrences occurred in the same patient in 4.7% (n = 67). Male gender, OBSTR, PERF, OBS-PERF, emergency operation, major medical and surgical complications, reoperation, TNM staging, tumor grading, and tumor venous invasion adversely affected DFS (p < 0.05). Multivariate analysis showed that OBS-PERF (p = 0.008), major medical complications (p = 0.011), reoperation (p = 0.018), TNM staging (p < 0.001), grading (p = 0.018), and venous invasion (p = 0.002) were independently associated with a poorer DFS. CONCLUSIONS: OBS-PERF colorectal cancer is associated with a poorer DFS, which may be worse than either OBSTR or PERF alone.

CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of ß-catenin and E-cadherin.

Elevated CUB-domain containing protein 1 (CDCP1) is predictive of colorectal cancer (CRC) recurrence and poor patient survival. While CDCP1 expression identifies stem cell populations that mediate lung metastasis, mechanisms underlying the role of this cell surface receptor in CRC have not been defined. We sought to identify CDCP1 regulated processes in CRC using stem cell populations, enriched from primary cells and cell lines, in extensive in vitro and in vivo assays. These experiments, demonstrating that CDCP1 is functionally important in CRC tumor initiation, growth and metastasis, identified CDCP1 as a positive regulator of Wnt signaling. Detailed cell fractionation, immunoprecipitation, microscopy, and immunohistochemical analyses demonstrated that CDCP1 promotes translocation of the key regulators of Wnt signaling, ß-catenin, and E-cadherin, to the nucleus. Of functional importance, disruption of CDCP1 reduces nuclear localized, chromatin-associated ß-catenin and nuclear localized E-cadherin, increases sequestration of these proteins in cell membranes, disrupts regulation of CRC promoting genes, and reduces CRC tumor burden. Thus, disruption of CDCP1 perturbs pro-cancerous Wnt signaling including nuclear localization of ß-catenin and E-cadherin.

Laparoscopic resection for diverticular disease: follow-up of 500 consecutive patients.

OBJECTIVE: To examine morbidity, mortality, conversion rates, and disease recurrence after laparoscopic resection of complicated and uncomplicated diverticular disease in a single center. SUMMARY BACKGROUND DATA: In contrast to colorectal cancer, there are few large studies of laparoscopic or open resection for diverticular disease. METHODS: This study represents a retrospective analysis of a prospectively collected database of all laparoscopic resections for uncomplicated and complicated diverticulitis from a single center. RESULTS: Five hundred patients (305 female) were identified (median age 58; range, 26-89). Recurrent diverticulitis was the most common indication for surgery (77%), followed by perforation (10%) and fistulation (9%). Median operating time was 120 minutes (range, 45-285) and median length of hospital stay was 4 (2-33) days. The splenic flexure was routinely mobilized. There was 1 (0.2%) 30-day and in-hospital death and 55 (11%) patients had major morbidity after the procedure. Conversion to an open operation was performed in 14 (2.8%) cases. Dense adhesions were the most common cause for conversion (6 patients). Among patients with complicated diverticulitis, the conversion rate was 5.3%, whereas for those with uncomplicated disease, it was 2.1% (P = ns). Operating time and length of hospital stay do not differ significantly between patients with complicated and uncomplicated diverticulitis. The conversion rate has come down from 8% for the first 100 cases to 1.5% for the last 400 cases (P = 0.002). To our knowledge, there have been no cases of recurrent diverticulitis. CONCLUSIONS: Laparoscopic resection even in complicated cases of diverticulitis is safe and effective. It can be achieved with short operating times and length of stay in conjunction with very low rates of morbidity and mortality. Adherence to surgical principles including routine mobilization of the splenic flexure and anastomosis onto the rectum may explain the absence of disease recurrence in our experience.

Development of an enzyme-linked immunosorbent assay for detection of CDCP1 shed from the cell surface and present in colorectal cancer serum specimens.

CUB domain containing protein 1 (CDCP1) is a transmembrane protein involved in progression of several cancers. When located on the plasma membrane, full-length 135kDa CDCP1 can undergo proteolysis mediated by serine proteases that cleave after two adjacent amino acids (arginine 368 and lysine 369). This releases from the cell surface two 65kDa fragments, collectively termed ShE-CDCP1, that differ by one carboxyl terminal residue. To evaluate the function of CDCP1 and its potential utility as a cancer biomarker, in this study we developed an enzyme-linked immunosorbent assay (ELISA) to reliably and easily measure the concentration of ShE-CDCP1 in biological samples. Using a reference standard we demonstrate that the developed ELISA has a working range of 0.68-26.5ng/ml, and the limit of detection is 0.25ng/ml. It displays high intra-assay (repeatability) and high inter-assay (reproducibility) precision with all coefficients of variation ≤7%. The ELISA also displays high accuracy detecting ShE-CDCP1 levels at ≥94.8% of actual concentration using quality control samples. We employed the ELISA to measure the concentration of ShE-CDCP1 in human serum samples with our results suggesting that levels are significantly higher in serum of colorectal cancer patients compared with serum from individuals with benign conditions (p<0.05). Our data also suggest that colorectal cancer patients with stage II-IV disease have at least 50% higher serum levels of ShE-CDCP1 compared with stage I cases (p<0.05). We conclude that the developed ELISA is a suitable method to quantify ShE-CDCP1 concentration in human serum.

Current status of laparoscopic and robotic ventral mesh rectopexy for external and internal rectal prolapse.

External and internal rectal prolapse with their affiliated rectocele and enterocele, are associated with debilitating symptoms such as obstructed defecation, pelvic pain and faecal incontinence. Since perineal procedures are associated with a higher recurrence rate, an abdominal approach is commonly preferred. Despite the description of greater than three hundred different procedures, thus far no clear superiority of one surgical technique has been demonstrated. Ventral mesh rectopexy (VMR) is a relatively new and promising technique to correct rectal prolapse. In contrast to the abdominal procedures of past decades, VMR avoids posterolateral rectal mobilisation and thereby minimizes the risk of postoperative constipation. Because of a perceived acceptable recurrence rate, good functional results and low mesh-related morbidity in the short to medium term, VMR has been popularized in the past decade. Laparoscopic or robotic-assisted VMR is now being progressively performed internationally and several articles and guidelines propose the procedure as the treatment of choice for rectal prolapse. In this article, an outline of the current status of laparoscopic and robotic ventral mesh rectopexy for the treatment of internal and external rectal prolapse is presented.

Hospital morbidity data for determining spread of disease at diagnosis for colorectal cancer: a validation study.

AIMS: There is currently no routine collection of cancer stages in population-based data in Australia. This study evaluates the accuracy of International classification of diseases (ICD) codes for secondary neoplasms recorded in hospital morbidity data to assign spread of disease at diagnosis for colorectal cancer. METHODS: The reference (gold) standard was the Australian clinicopathological stage (ACPS) documented by a treating colorectal surgeon and derived from histopathology and clinical findings. To allow comparison with stages derived from the hospital morbidity data (HMD), ACPS was mapped to the spread of disease (local, regional and distant). Sensitivity, specificity and positive-predictive values were calculated to compare the accuracy of stage derived from HMD. RESULTS: Data from both the reference standard and HMD were available for 499 patients. HMD slightly overestimated patients with local disease (62.3 vs 56.9%). There was a corresponding underestimation of regional and distant spread of disease. While sensitivity for regional and distant disease was moderate (66.4 and 71.4%, respectively), specificity was high (92.7 and 96.6%, respectively). CONCLUSION: ICD codes for secondary neoplasms in HMD are limited in their utility for determining the spread of disease for colorectal cancer. Clinicians need to ensure that clinical coders are provided with enough information to accurately code for spread of disease. We recommend reporting histopathology in a synoptic format which includes background information on the presence or absence of distant metastasis and the tumor node metastasis stage.

Laparoscopic restorative proctectomy - hybrid approach or totally laparoscopic?

BACKGROUND: Laparoscopic rectal resection is now a technique that is emerging from experience with laparoscopic colonic resection. We review and present our experience with restorative proctectomy for cancer and compare those performed with a hybrid technique with those performed totally laparoscopically. METHODS: A total of 177 patients have undergone laparoscopic restorative proctectomy. All of the patients were planned to have the abdominal portion of their surgery performed laparoscopically and to convert to open for the rectal dissection as required. They were then stratified into those that had their surgery performed completely laparoscopically (laparoscopic group - LG), and to those who had their rectal dissection and or transection performed with an open incision (hybrid group - HG). RESULTS: Short-term outcomes were compared between the LG (n=103) and the HG (n=74). The overall complication rate was higher in the HG (12% versus 35% P<0.001), mainly with a significantly higher pelvic abscess rate and higher rate of post-operative ileus. There were no intraoperative or post-operative deaths. Length of stay was equivalent in both groups (five days). To date, distal recurrence has occurred in 7.7% of the patients, eight in the LG and four in the HG (NS). Two patients, one in each group, have had local recurrence only. CONCLUSIONS: Laparoscopic open or laparoscopic hybrid approaches are techniques that can be used in suitable patients. Both have acceptable morbidity and mortality.

The impact of Creutzfeldt-Jakob disease on surgical practice.

Creutzfeldt-Jakob disease (CJD) is characterised by abnormal prion protein that can replicate and replace nervous tissue, with rapid lethal neurodegenerative consequences. The transmissible nature of CJD has been known for half a century and transmission has occurred through neurosurgical procedures. Variant Creutzfeldt-Jakob disease (vCJD) emerged in 1996, and the presence of abnormal prion in lymphatic tissue extended the number of surgical specialties dealing with infected material; transmission through blood transfusion raised the possibilities of a large carrier pool and spread of epidemic proportion. The abnormal prion is difficult to remove and this could influence future decontamination programmes. Contaminated instruments must be withdrawn from surgical practice, and this can interfere with the efficient running of a surgical unit and optimal patient care. There is an urgent need for reliable methods for the detection of abnormal prion, within and outside the body. These will help to clarify the epidemiology of CJD, and to reduce its transmission via blood and tissue. They will also allow determination of the efficacy of new decontamination products in surgical practice, and the value of any treatment of sufferers and carriers of CJD. In the meantime, continued vigilance and informed regulation of all aspects of CJD must remain.