Total Mesorectal Excision In Patients Research Articles

Factors influencing histopathology-assessed TME quality after low anterior rectal resection: Results of a prospective multicenter observational trial.

3547 Background: Total mesorectal excision (TME) has become standard of care in rectal cancer surgery, leading to a massive reduction in local recurrence rate. However, incomplete TME is associated with an increase in local recurrences. To date, there are no reliable data on clinical factors predicting incomplete TME in patients undergoing rectal cancer surgery. We used the data set of the German Quality Assurance in Rectal Cancer Surgery prospective multicenter observational trial to investigate this issue under routine clinical care conditions. Methods: This is a retrospective analysis of a prospectively gathered data set involving >300 German hospitals of all levels of care. Patients undergoing low anterior rectal resection for rectal cancer between 01/01/05 and 12/31/09 were included. Multivariate analysis using a stepwise logistic regression model was performed in order to identify factors predicting suboptimal TME as determined at postoperative histopathology. Risk factors analyzed included age, BMI, tumor distance from the anal verge, neoadjuvant therapy, duration of surgery, surgeon experience, laparoscopic vs. open approach, dissection technique, intraoperative complications, and pT stage. Results: A total of 6,179 patients were included. Due to missing data for one or more parameters 1,573 patients had to be removed from the data set, leaving 4,606 patients for analysis. pT stage >2 (OR 1.22), tumor distance from the anal verge <8 cm (OR 1.27), advanced age (>65 years, OR 1.24; >80 years, OR 1.59), presence of intraoperative complications (OR 2.06), monopolar dissection technique (OR 1.44), and low experience of the operating surgeon (OR 1.20) were identified as being independently associated with moderate or poor TME quality. Conclusions: This is the largest analysis of factors predicting incomplete TME to date. Since good TME quality is a prerequisite for a low recurrence rate, rectal cancer surgery should be performed or supervised by experienced colorectal surgeons. Monopolar pelvic dissection technique should be avoided. On the other hand, laparoscopic approach and use of neoadjuvant therapy do not seem to increase the risk for incomplete TME.

Anastomotic leakage after laparoscopic total mesorectal excision for low rectal cancer

Aim: Our single centre comparative study is focused on perioperative outcomes of laparoscopic total mesorectal excision in patients with middle and low rectal cancer with attention to complications of double stapling coloanal anastomosis with and without protective ileostomy. Material and methods: From 1 January 2005 to 30 June 2008, 349 patients with rectal cancer underwent surgery at our centre. Of these, 114 patients (41 women and 73 men) with middle and low rectal cancer (≤ 12 cm from the anal verge) after laparoscopic resection with total mesorectal excision and primary coloanal anastomosis were included in the study. There were 64 patients with primary anastomosis without protective ileostomy in the first group, and 50 patients with primary protective ileostomy in the second one. Anastomotic leakage was defined as presence of stapler line dehiscence, presacral abscess or rectovaginal fistula. Results: Coloanal anastomotic leakage was present in 11.4% of cases (13 of 114 patients). In the no stoma group leakage was present in 17.2% of cases, in the stoma group in 4.0% of cases. Reoperation was needed in 9.4% (6 of 64) in the no stoma group and in 2.0% (1 of 50) in the stoma group. Stage of disease was found to be another factor influencing anastomotic healing. There was no significant difference between groups in relation to preoperative chemoradiotherapy, sex, body mass index, ASA score, age, time of surgery and tumour location in our study. Conclusions: Protective loop ileostomy significantly reduces the presence of symptomatic anastomotic leakage of double stapling coloanal anastomosis after laparoscopic total mesorectal excision in patients with low rectal cancer.

EXPERT-C: A randomized phase II European multicenter trial of neoadjuvant chemotherapy (capecitabine/oxaliplatin) and chemoradiation (CRT) with or without cetuximab followed by total mesorectal excision (TME) in patients with MRI-defined high-risk rectal cancer.

360 Background: We previously demonstrated the feasibility of administering neoadjuvant chemotherapy before CRT and TME in patients with MRI selected poor prognosis rectal cancer (Chua Y J et al Lancet Oncol 2010). This trial evaluates the addition of the anti-EGFR antibody cetuximab to this treatment strategy. KRAS and BRAF mutations have been established as predictive for lack of response to anti-EGFR therapy in metastatic colorectal cancer. Methods: Patients with newly diagnosed, histologically confirmed, MRI defined high risk rectal adenocarcinoma were randomised to receive 4 cycles of capecitabine 1,700mg/m2 with oxaliplatin 130mg/m2 (CAPOX) followed by CRT, 45Gy/25# + 5.4Gy/3# boost with concurrent continuous capecitabine 1,650mg/m2/day, TME and 4 cycles of adjuvant CAPOX (EXPERT) or the same regimen with the addition of cetuximab (400mg/m2 loading dose week 1, followed by 250mg/m2/week) (EXPERT-C). The primary endpoint is complete response (CR) (defined as pathological complete response or radiological complete response in patients who decline surgery) in KRAS and BRAF wild type tumours. Secondary endpoints include radiological response to CRT, CR in both KRAS wild type and mutant patients, R0 resection rates, progression free and overall survival and safety. Results: Between 2005-2008, 165 eligible patients were recruited from 15 centres (EXPERT n=81, EXPERT-C n=84). 99% of patients had performance status 0-1, 98% had ≥ T3 disease, 56% had an involved or threatened circumferential resection margin and 72% had evidence of extramural venous invasion determined by MRI. The current median follow up is 30 months. 72/81 (89%) and 79/84 (94%) of patients completed neoadjuvant CRT and 72/81 (89%) and 77/84 (92%) patients underwent curative-intent surgery on the EXPERT and EXPERT-C arms respectively. Two patients declined surgery. Conclusions: The primary and secondary endpoints will be analyzed in October 2010 and will be presented at the meeting. [Table: see text]

The Prognostic Value of Lymph Node Ratio After Neoadjuvant Chemoradiation and Rectal Cancer Surgery

Neoadjuvant chemotherapy decreases total lymph nodes harvested and possibly affects lymph node staging after total mesorectal excision in patients with rectal cancer. This study aimed to compare staging by lymph node ratio with staging by absolute number of positive lymph nodes. This study is a retrospective cohort review. : A tertiary care referral center was the setting for this investigation. A total of 281 consecutive patients who underwent neoadjuvant chemoradiation and total mesorectal excision after histologically confirmed rectal cancer between January 1, 1998 and December 31, 2008 were included in this study. Lymph node ratio is the number of positive lymph nodes divided by the total number of lymph nodes within one sample. Risk categories of low (0 to < 0.09); medium (0.09 to < 0.36); and high (≥ 0.36) for lymph node ratio were chosen by significance with the use of Cox proportional hazards models. These categories were then used in a reclassification table and compared with positive lymph node stage: low (0 positive nodes), medium (1-3 nodes), and high (> 3) by 5-year mortality rates. The majority (87%) of patients were concordant in risk assessment. Thirty patients were downstaged to lower risk lymph node ratio categories without showing actual lower mortality rates. Seven patients were upstaged to a high-risk lymph node ratio category with a supporting higher 5-year mortality rate. When limiting the analysis to those with fewer than 12 nodes, 136 (95%) patients were concordant in risk assessment; all 30 incorrectly downstaged patients were removed, but the 7 correctly upstaged patients remained. Patients who undergo neoadjuvant chemoradiation before rectal cancer surgery frequently have fewer than 12 lymph nodes harvested despite maintaining vigorous surgical standards. Lymph node ratios may provide excellent prognostic value and are possibly a better independent staging method than absolute positive lymph node counts when less than 12 lymph nodes are harvested after neoadjuvant treatment.

Defunctioning ileostomy closure following low anterior resection by chemotherapy

The aim of this study is to review the time between formation and closure of loop ileostomies following total mesorectal excision in patients with rectal cancer. A retrospective study of 170 patients who underwent low anterior resection for rectal cancer, between 1990 and 2009. Loop ileostomies were created in 8 patients. Of the 8 patients with defunctioning loop ileostomies, 4 received adjuvant chemo-radiotherapy, 3 received neo-adjuvant chemo-radiotherapy and 1 did not receive anything. There was 12.5% morbidity. The time from formation to closure for the patient with no adjuvant therapy was 3 months and for those with adjuvant therapy was 7 months. This was a significant delay. Time between formation and closure of loop ileostomy following anterior resection of rectum is significantly delayed by adjuvant chemotherapy.

Adjuvant radiotherapy following total mesorectal excision for stage IIA rectal cancer: is it beneficial?

The benefit of adjuvant radiotherapy in patients with stage IIA (T3N0) rectal cancer following total mesorectal excision (TME) is controversial. We evaluated the effect of adjuvant chemoradiotherapy (CRT) versus chemotherapy (CT) alone on the local recurrence and survival of patients with stage IIA rectal cancer after TME. Between 1996 and 2004, patients with stage IIA rectal cancer who received adjuvant CT (n = 29) or CRT (n = 122) following TME were enrolled. Oncologic outcomes were compared between groups, and risk factors for local recurrence and overall survival rates were analyzed. The median follow-up period was 78 months. No significant differences were observed in the 5-year local recurrence (3.4% versus 9.0%; P = 0.348) or 5-year overall survival rates (86.2% versus 80.3%; P = 0.924) between CT and CRT. However, involvement of the circumferential resection margin and age >60 years were associated with adverse oncologic outcomes. Additional postoperative radiotherapy did not alter local recurrence or survival after TME in patients with stage IIA rectal cancer. Postoperative radiation may be an overtreatment as an adjuvant therapy in patients with stage IIA rectal cancer if they had no other risk factors. However, randomized controlled trials are warranted to confirm this suggestion.

Technical feasibility of laparoscopic total mesorectal excision for patients with low rectal cancer after concurrent radiation and chemotherapy with bevacizumab plus FOLFOX

This study aimed to evaluate the technical feasibility of laparoscopic total mesorectal excision (TME) for the treatment of low rectal cancer after concurrent chemoradiation therapy (CCRT) with bevacizumab and FOLFOX. Patients with clinical T3, T4, or N1-2 rectal cancer were subjected to a preoperative CCRT protocol with FOLFOX and bevacizumab (5 mg/kg) biweekly for 6 cycles followed by a standardized laparoscopic TME procedure, as detailed in the attached video. The treatment protocol was completed by 28 patients. Scrutiny of the video indicated that the dissection plane was a little blurred due to preoperative CCRT, but this did not significantly increase the technical difficulties. Laparoscopic TME was efficiently performed with acceptable operation time (214.4 ± 44.4 min). However, the median blood loss (420 ml; range, 120-1,200 ml) in this series was significantly greater than in the historic series without bevacizumab therapy. Bevacizumab seems not to increase the severity of FOLFOX-related liver steatosis and sinusoidal dilation. One operative mortality (3.6%) occurred. Six patients (21.4%) presented with postoperative complications including upper gastrointestinal bleeding, deep vein thrombosis, pelvic abscess, wound infection, enterocutaneous fistula, and perineal fistula. The patients presented with mild postoperative pain and had a quick convalescence. The addition of bevacizumab to FOLFOX achieved a superior pathologic response for 78.3% of the patients, whose residual tumor cells were very few (< 10% microscopic field). Based on the controllable surgical complications and minimal invasiveness in the current patient series, laparoscopic TME is shown to be technically feasible and can be recommended for patients with advanced lower rectal cancer requiring preoperative CCRT using bevacizumab as the additional therapeutic agent.

Quality of surgery for rectal carcinoma: comparison between open and laparoscopic approaches

Background Macroscopic evaluation of a tumor specimen is an independent prognostic factor of oncologic outcome after total mesorectal excision (TME) for rectal cancer. This study aimed to assess macroscopic quality of specimens acquired after laparoscopic versus open TME in patients with low rectal cancer. Patients and methods Seventy-two patients with low rectal cancer underwent TME either by open (n = 39) or laparoscopic (n = 33) approach. In all specimens, the cut edge of the peritoneal reflection at the anterior mid-rectum, the Denonvillier's fascia, the visceral fascia covering the mesorectum both posteriorly and laterally, and the bowel wall below the mesorectum were macroscopically assessed. Results Colorectal anastomoses were located significantly lower in the laparoscopic than in the open group ( P < .001). The Denonvillier's fascia was violated in 7 patients after open surgery ( P = .01). A significantly more complete TME with intact visceral pelvic fascia was performed after laparoscopy compared with open surgery ( P = .025). Conclusions Laparoscopy offers a macroscopically more complete specimen after TME for rectal cancer than the open approach because it offers a better view in the pelvis.

Patterns of Failure and Local Control After Intraoperative Electron Boost Radiotherapy to the Presacral Space in Combination with Total Mesorectal Excision in Patients with Locally Advanced Rectal Cancer

To evaluate local control and patterns of failure in patients treated with intraoperative electron beam radiotherapy (IOERT) after total mesorectal excision (TME), to appraise the effectiveness of intraoperative target definition. We analyzed the outcome of 243 patients with rectal cancer treated with IOERT (median dose, 10 Gy) after TME. Eighty-eight patients received neoadjuvant and 122 patients adjuvant external beam radiotherapy (EBRT) (median dose, 41.4 Gy), and in 88% simultaneous chemotherapy was applied. Median follow-up was 59 months. Local failure was observed in 17 patients (7%), resulting in a 5-year local control rate of 92%. Only complete resection and absence of nodal involvement correlated positively with local control. Considering IOERT fields, seven infield recurrences were seen in the presacral space, resulting in a 5-year local control rate of 97%. The remaining local relapses were located as follows: retrovesical/retroprostatic (5), anastomotic site (2), promontorium (1), ileocecal (1), and perineal (1). Intraoperative electron beam radiotherapy as part of a multimodal treatment approach including TME is a highly effective regimen to prevent local failure. The presacral space remains the site of highest risk for local failure, but IOERT can decrease the percentage of relapses in this area.

H-ras Inhibits RhoA/ROCK Leading to a Decrease in the Basal Tone in the Internal Anal Sphincter

The present studies evaluated the role of H-ras and its implications in the RhoA/Rho kinase (ROCK) pathway in regulating basal tone in the internal anal sphincter (IAS). Studies were performed in the IAS from the wild-type (H-ras(+/+)) and knock-out (H-ras(-/-)) mice. The basal tone of smooth muscle strips was measured by isometric force transducers. Length of smooth muscle cells (SMC) isolated from the IAS in the basal state was determined by phase contrast microscopy. Experiments were repeated in the presence of Y 27632, a ROCK inhibitor. Involvement of the RhoA/ROCK machinery was analyzed by reverse-transcription polymerase chain reaction, Western blot, and immunocytochemistry. Reversal of H-ras knock-out effect was evaluated by transfection of SMCs with the constitutively activated (G12V) mutant. Basal tone of the H-ras(-/-) IAS was significantly higher and resistant to relaxation by Y 27632, compared with the H-ras(+/+) IAS. Similarly, the length of SMCs from H-ras(-/-) IAS was significantly shorter. Y 27632 eliminated this difference. RhoA immunoreactivity shifted from cytoplasm to plasma membrane in H-ras(-/-) SMCs, a change typically associated with contraction. Further, SMCs from H-ras(-/-) mice exhibited higher levels of the contractile proteins ROCK II, phosphorylated-MYPT(1) and phosphorylated-MLC(20). Transfection with the G12V mutant increased the length of H-ras(-/-) cells. Conversely, the dominant negative H-ras (S17N) mutant decreased the length of H-ras(+/+) cells. H-ras negatively regulates basal tone in the IAS by inhibiting RhoA/Rho-kinase machinery. Studies may have significant relevance in the pathophysiology and therapy of certain anorectal motility disorders associated with the IAS dysfunction.

Following anterior resection for rectal cancer, defunctioning ileostomy closure may be significantly delayed by adjuvant chemotherapy: a retrospective study

A temporary loop ileostomy is often created to minimize the impact of peritoneal sepsis from an anastomotic dehiscence following colo-anal or low colorectal anastomosis. These stomas are not without complications. Clinicians tend to advise patients that their loop ileostomy will be reversed within 6-12 weeks of formation. However, factors such as adjuvant chemotherapy may affect the timing of closure. The aim of this study was to review the time between formation and closure of loop ileostomies following total mesorectal excision in patients with rectal cancer. A retrospective study of 50 patients with loop ileostomies to defunction total mesorectal excisions for rectal cancer, between April 2002 and July 2005. Of the 50 patients with defunctioning loop ileostomies, 24 received adjuvant chemo-radiotherapy, and 26 did not. There was a 28% morbidity. The overall median time from formation to closure was 142 days (35-575). Median time from formation to closure in those with adjuvant therapy was 197 days (35-575) and in those with no adjuvant therapy was 133 days (75-395). This was a significant delay (P = 0.049). Sixteen stomas were not closed to date. Time between formation and closure of loop ileostomy following anterior resection of rectum is significantly delayed by adjuvant chemotherapy. Because of their high morbidity, defunctioning ileostomies should be closed as early as medically possible, especially if adjuvant chemotherapy is planned.

A prospective evaluation of anorectal function after total mesorectal excision in patients with a rectal carcinoma

Background. Rectum resection with total mesorectal excision (TME) and neorectal anastomosis often compromises anorectal function. Insight into the underlying mechanisms is lacking. Therefore, a prospective study was designed to investigate the relationship between clinical and functional outcomes preoperatively and postoperatively. Methods. Eleven patients with rectal cancer were examined before and 4 and 12 months after surgery and compared with 11 healthy volunteers (HVs). Anorectal (neorectal) function was examined by clinical outcome questionnaire, anal manometry, rectal compliance, and sensation. Six HVs also underwent barostat measurements in the sigmoid colon. Results. Clinical parameters of soiling and passive incontinence (loss of stool without sensation) increased significantly until 12 months postoperatively, whereas urgency and tenesmus increased temporarily, returning to preoperative values at 12 months. In anorectal measurements, anal sphincter function was grossly preserved; however, rectal-anal inhibitory reflex (RAIR) was decreased at 4 months but recovered after 1 year. Neorectal compliance was similar to that of HV sigmoid, increasing slightly after 12 months but still significantly lower than that of normal rectum. Neorectal sensation to pressure distention was similar to that of normal rectum, however accompanied by smaller volumes. Neorectal distention induced contractions of large amplitude at 4 months, returning to normal after 12 months. Conclusions. Our results suggest that the transient increase in urgency and tenesmus after surgery results from a temporary increase in neorectal “irritability” accompanied by some adaptation of compliance in time. In contrast, episodes of incontinence and soiling are increased after 1 year most likely because of reduced neorectal capacity and RAIR recovery in the presence of a low basal anal sphincter pressure. (Surgery 2003;133:56-65.)