Systematic review and meta-analysis of local resection or transanal endoscopic microsurgery versus radical resection in stage i rectal cancer: A real standard?

Current guidelines recommend radical resection for stage I rectal cancer. However, since screening programs are being installed, an increasing number of cancers are being detected in early stages. Endoscopic resection is often performed at the time of diagnosis. This systematic review was undertaken to review the evidence on endoscopic approach vs. radical resection for stage I rectal cancer. Recommendations were issued based on the GRADE methodology and risk stratification used in clinical practice. A systematic search (until March 2015) identified 2 meta-analyses and 1 additional randomized trial. For the primary outcomes (overall survival, disease-free survival, local recurrence-free survival and metastasis-free survival) no evidence could be found on the superiority of local or radical resection. Secondary outcomes (blood loss, hospital stay, operative time, number of permanent stomas and perioperative deaths) were in favour of local resection. The authors strongly recommend radical resection for T2 rectal cancer, but consider 'en bloc' local resection sufficient for pT1 sm1 rectal cancers when confirmed pathologically. Discussion by a multidisciplinary team and adequate surveillance remain mandatory.

Accuracy of pre-treatment locoregional rectal cancer staging in a national improvement project.

BACKGROUND: The aim of this study was to assess the accuracy, particularly the predictive value, of locoregional clinical rectal cancer staging (cTN) and its variability in a national improvement project. METHODS: cTN stages and the distance between tumour and mesorectal fascia (MRF) were compared with histopathological findings in 1168 patients who underwent radical resection without neoadjuvant treatment. Data were registered prospectively from 2006 to 2014. RESULTS: Agreement between clinical and histopathological TN stages was 50%, independent of tumour location. Inter-hospital variability was within 99% prediction limits. Magnetic resonance imaging (MRI) was increasingly applied, but staging accuracy did not improve. Stage II-III was correctly predicted in 69% and pStage I was over-staged in 35%. The positive predictive value of endorectal ultrasonography (ERUS) for T1 lesions was 57%. MRI-based distances to MRF correlated poorly with the circumferential resection margin (r = 0.26). A negative resection margin was achieved in 91% when the distance to the MRF was >1 mm. CONCLUSIONS: The accuracy of rectal cancer staging in general practice should be improved to avoid under- or overtreatment. Training and expert review of pre-treatment MR imaging could be helpful. A second ERUS is justified when transanal local resection for early lesions is planned.

Survival among clinical stage I-III rectal cancer patients treated with different preoperative treatments: A population-based comparison.

BACKGROUND: Radical resection is regarded as the cornerstone of rectal cancer treatment. Preoperative (chemo)radiotherapy and adjuvant chemotherapy are often administered. This population-based study compares the survival in clinical stage I-III rectal cancer patients who received either preoperative radiotherapy, preoperative chemoradiotherapy or no preoperative therapy. As secondary research questions, the association of type of radical resection and adjuvant chemotherapy on survival is also investigated. METHODS: Patients diagnosed between January 2006 and December 2011 with stage I-III rectal adenocarcinoma were retrieved from the Belgian Cancer Registry database. Multivariable Cox proportional hazards regression models were applied to evaluate the association of preoperative treatment, type of radical resection and use of adjuvant chemotherapy with survival, adjusting for the baseline characteristics age, gender, WHO performance status and clinical stage. RESULTS: A total of 5173 rectal cancer patients were identified. Preoperative treatment was as follows: none in 1354 (26.2%), radiotherapy in 797 (15.4%) and chemoradiotherapy in 3022 (58.4%) patients. The patient group who did not receive preoperative therapy or radiotherapy followed by radical resection had a lower observed survival compared to the patient group receiving preoperative chemoradiotherapy. The patient groups who underwent abdominoperineal excision and those receiving adjuvant chemotherapy had a worse observed survival compared to the patient group treated with sphincter-sparing surgery and no adjuvant therapy respectively. These effects were age-dependent. Multivariable analysis demonstrated similar findings for the observed survival conditional on surviving the first year since surgery. CONCLUSION: In this population-based study among clinical stage I-III rectal cancer patients treated with radical resection, a superior observed survival was noticed in the patient group receiving preoperative chemoradiotherapy compared to the patients groups receiving no or preoperative radiotherapy only, adjusting for case mix, type of radical resection and adjuvant chemotherapy. Additionally, higher adjusted observed survival was also detected for the patient groups with sphincter-sparing surgery or no adjuvant chemotherapy.

Quantitative contribution of prognosticators to oncologic outcome after rectal cancer resection.

BACKGROUND: Prognostication is an important aspect of medical practice. It relies on statistical modeling testing the correlation of variables with the outcome of interest. OBJECTIVE: In contrast with the classic approach of predictive modeling, this study aimed to estimate the unique, individual, and relative contributions. This includes the quantitative contributions of patient-, tumor-, and treatment-related factors to oncologic outcome after rectal cancer resection. DESIGN: This was a retrospective analysis of prospectively registered data. SETTINGS: The study included 65 hospitals participating on a voluntary basis in the Project on Cancer of the Rectum, a Belgian multidisciplinary improvement project of rectal cancer care. PATIENTS: A total of 1470 patients presenting midrectal or low-rectal adenocarcinoma without distant metastasis were included. INTERVENTION: The study intervention was total mesorectal excision with or without sphincter preservation. MAIN OUTCOME MEASURES: The unique, individual, and relative contributions of a set of covariables to the statistical variability of the distant metastasis rate and overall survival have been calculated. RESULTS: The 5-year distant metastasis rate was 21% and overall survival 76%. A large amount of the variability of the outcomes (ie, 83.6% to 84.2%) could not be predicted by the prognostic factors. Unique contributions of the predictors ranged from 0.1% to 3.1%. The 3 risk factors with the highest unique contribution for distant metastasis were lymph node ratio, pathologic tumor stage, and total mesorectal quality; for overall survival they were age, lymph node ratio, and ASA score. LIMITATIONS: The main weakness of this study was incomplete participation and registration in the Project on Cancer of the Rectum. CONCLUSIONS: Several factors influence oncologic outcomes and are present in prediction models. However, the models predict relatively little of outcome variation.

Clinical outcome after radical excision of moderate-severe endometriosis with or without bowel resection and reanastomosis: a prospective cohort study.

OBJECTIVE: To assess the clinical outcome of women requiring laparoscopic excision of moderate-severe endometriosis in women with and without bowel resection and reanastomosis. METHODS: Two hundred three patients with laparoscopically excised moderate (n = 67) or severe (n = 136) endometriosis (rAFS: revised endometriosis classification of the American Fertility Society) were prospectively followed during a median of 20 months (1-45 months) using a CONSORT-inspired checklist. Patients completed the EHP30 Quality-of-Life Questionnaire and visual analogue scales (VAS) for dysmenorrhea, chronic pelvic pain, and deep dyspareunia and answered questions about postoperative complications, reinterventions/recurrences, and fertility outcome 1 month before and 6, 12, 18, and 24 months after surgery. Clinical outcome was compared between women with deeply infiltrative endometriosis undergoing CO2 laser ablative surgery with bowel resection (study group, 76/203; 37%) and without bowel resection (control group, 127/203; 63%). RESULTS: Both groups were similar with respect to population characteristics and clinical outcome, except for mean rAFS score [higher in study group (73 ± 31) than in control group (48 ± 26)] and minor complication rate [higher in study group (11%) than in control group (1%)]. In both groups, mean VAS and EHP30 scores improved significantly and remained stable for 24 months after surgery, with a pregnancy rate of 51%. Within 1, 2, and 3 years follow-up, the cumulative reintervention rate was 1%, 7%, and 10%, respectively, and the cumulative endometriosis recurrence rate was 1%, 6%, and 8%, respectively. CONCLUSIONS: Clinical outcome after CO2 laser laparoscopic excision of moderate-severe endometriosis was comparable in women with or without bowel resection and reanastomosis, except for a higher minor complication rate occurring in women with bowel resection and reanastomosis (NCT00463398).

Fecal continence revisited: the anal external sphincter continence reflex.

BACKGROUND: None of the current theories on fecal incontinence can explain fecal continence adequately. OBJECTIVE: This study aims to evaluate the mechanism controlling fecal continence. DESIGN: Anal electrosensitivity, anorectal pressures, and rectal pressure volumetry tests were performed in 17 controls before and after superficial local anal anesthesia and in 6 controls before and after spinal anesthesia. The same tests were performed in 1 patient before and after injected local anal anesthesia and in 3 patients with spinal cord lesions at levels Th3 to L3. RESULTS: After superficial local anal anesthesia, anal electrosensitivity decreased, but basal anal pressure remained unaltered. Squeeze pressure decreased and rectal filling sensation levels remained. Local anesthesia reduced anal pressure recorded in the distal anal canal during progressive rectal filling. This was also the case, albeit more explicit, after the local anal anesthetic was injected. After spinal anesthesia, the anal canal became insensitive to electric stimulation, but basal and squeeze pressure values decreased substantially, and the increase in anal pressure during the balloon-retaining test disappeared completely. In the patients with spinal cord lesions, the external sphincter could not be squeezed on command, but during the balloon-retaining test, the anal sphincter did squeeze autonomously at more than 300 mmHg. LIMITATIONS: These were partially experimental measurements. The relevance of the found model in the daily clinical practice will have to be studied in a following study. CONCLUSIONS: Our results support the hypothesis that the component of fecal continence mediated by contraction of the external sphincter depends on a anal external sphincter continence reflex without involving the brain. Presumably, the afferent receptors of this reflex are contact receptors located superficially in the mucosa or submucosa of the distal anal canal. A nonfunctioning anal external sphincter continence reflex would, therefore, result in fecal incontinence (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A116).

Waist circumference and waist/hip ratio are better predictive risk factors for mortality and morbidity after colorectal surgery than body mass index and body surface area.

OBJECTIVES: To determine whether body fat distribution, measured by waist circumference (WC) and waist/hip ratio (WHR), is a better predictor of mortality and morbidity after colorectal surgery than body mass index (BMI) or body surface area (BSA). BACKGROUND: Obesity measured by BMI is not a consistent risk factor for postoperative mortality and morbidity after abdominal surgery. Studies in metabolic and cardiovascular diseases have shown WC and WHR to be better outcome predictors than BMI. METHODS: A prospective multicenter international study was conducted among patients undergoing elective colorectal surgery. The WHR, BMI, and BSA were derived from body weight, height, and waist and hip circumferences measured preoperatively. Uni- and multivariate analyses were performed to identify risk factors for postoperative outcomes. RESULTS: A total of 1349 patients (754 men) from 38 centers in 11 countries were included. Increasing WHR significantly increased the risk of conversion [odds ratio (OR) = 15.7, relative risk (RR) = 4.1], intraoperative complications (OR = 11.0, RR = 3.2), postoperative surgical complications (OR = 7.7, RR = 2.0), medical complications (OR = 13.2, RR = 2.5), anastomotic leak (OR = 13.7, RR = 3.3), reoperations (OR = 13.3, RR = 2.9), and death (OR = 653.1, RR = 21.8). Both BMI (OR = 39.5, RR = 1.1) and BSA (OR = 4.9, RR = 3.1) were associated with an increased risk of abdominal wound complication. In multivariate analysis, the WHR predicted intraoperative complications, conversion, medical complications, and reinterventions, whereas BMI was a risk factor only for abdominal wall complications; BSA did not reach significance for any outcome. CONCLUSIONS: The WHR is predictive of adverse events after elective colorectal surgery. It should be used in routine clinical practice and in future risk-estimating systems.

Risk adjusted benchmarking of abdominoperineal excision for rectal adenocarcinoma in the context of the Belgian PROCARE improvement project.

OBJECTIVE: The abdominoperineal excision (APE) rate, a quality of care indicator in rectal cancer surgery, has been criticised if not adjusted for confounding factors. This study evaluates variability in APE rate between centres participating in PROCARE, a Belgian improvement initiative, before and after risk adjustment. It also explores the effect of merging the Hartmann resections (HR) rate with that of APE on benchmarking. DESIGN: Data of 3197 patients who underwent elective radical resection for invasive rectal adenocarcinoma up to 15 cm were registered between January 2006 and March 2011 by 59 centres, each with at least 10 patients in the registry. Variability of APE or merged APE/HR rates between centres was analysed before and after adjustment for gender, age, ASA score (3 or more), tumour level (rectal third), depth of tumour invasion (cT4) and preoperative incontinence. RESULTS: The overall APE rate was 21.1% (95% CI 19.7 to 22.5%). Significant variation of the APE rate was observed before and after risk adjustment (p<0.0001). For cancers in the lower rectal third, the overall APE rate increased to 45.8% (95% CI 43.1 to 48.5%). Also, variation between centres increased. Risk adjustment influenced the identification of outliers. HR was performed in only 2.6% of patients. However, merging of risk adjusted APE and HR rates identified other centres with outlying definitive colostomy rates than APE rate alone. CONCLUSION: Significant variation of the APE rate was observed. Adjustment for confounding factors as well as merging HR with APE rates were found to be important for the assessment of performances.

Intersphincteric proctectomy with end-colostomy for anorectal Crohn's disease results in early and severe proximal colonic recurrence.

BACKGROUND: Perianal Crohn's disease (CD) represents a more aggressive phenotype of inflammatory bowel disease and often coincides with proctocolitis. This study aims to assess the outcome of patients undergoing proctectomy with end-colostomy. METHODS: A retrospective outcome analysis of 10 consecutive patients who underwent intersphincteric proctectomy with end-colostomy between February 2007 and May 2011 was performed. All patients suffered from refractory distal and perianal CD. The proximal colon was normal at endoscopy. All data were extracted from a prospectively maintained database. The main outcome parameter was disease recurrence and need for completion colectomy. RESULTS: Severe and early endoscopic recurrence in the proximal colon occurred in 9/10 patients at a median time interval of 9.5 months (range: 1.9-23.6 months). Despite protracted medical treatment, completion colectomy was necessary in 5 patients. One patient, who underwent a second segmental colectomy with a new end-colostomy, showed again endoscopic recurrence and is currently treated with anti-TNF agents. CONCLUSIONS: Intersphincteric proctectomy with colostomy seems to be an ineffective surgery for perianal CD with coexisting proctitis and results in a high risk of recurrence of the disease in the remaining colon. Therefore, despite a normal appearance of the proximal colon, a proctocolectomy with end-ileostomy seems to be the surgical approach of choice in these patients.

Investigation of possible endogenous hypoxia markers in colorectal cancer.

OBJECTIVE: We evaluated the potential of some recently proposed hypoxia markers, being monocarboxylic acid transporter 1 (MCT1), MCT4 and prolyl hydroxylase 2 (PHD2); and a more established hypoxia marker, glucose transporter-1 (GLUT-1), by testing the association with the exogenous marker pimonidazole. MATERIALS AND METHODS: Paraffin embedded tumour sections of 20 colorectal cancer patients were stained for blood vessels together with either pimonidazole or carbonic anhydrase-IX (CA-IX) and single stained for MCT1, MCT4, GLUT-1, and PHD2. Expression of all markers was compared with expression of pimonidazole and micro-vessel density (MVD) and with disease-free survival (DFS) and overall survival (OS). RESULTS: No correlation was found between the different intrinsic hypoxia markers tested and pimonidazole. A trend for high MCT1 expression in biopsies with low CA-IX expression was found (R = -0.45, p = 0.06) and also the expression of MCT1 was higher in tumours with a high MVD (R = 0.49, p = 0.04). The more advanced tumours showed a higher expression of GLUT-1 (p = 0.03). A low CA-IX expression in the tumour correlated with better DFS (p = 0.03) and related to better OS (p = 0.07). CONCLUSION: Although none of the tested intrinsic hypoxia markers correlated with pimonidazole staining, we confirmed the important role of both GLUT-1 and CA-IX for a more advanced pTNM (pathological tumour-node-metastasis) stage and DFS respectively.

Pelvic exenterations for gynecological malignancies: a study of 36 cases.

OBJECTIVE: Evaluation of surgical outcomes, survival, and morbidity associated with pelvic exenteration (PE) performed for gynecologic malignancies. METHODS: Review of 36 consecutive patients who underwent PE between June 1999 and April 2010. RESULTS: Pelvic exenteration was performed for cancer of the cervix (n = 18), endometrium (n = 9), vagina/vulva (n = 8), and ovary (n = 1). Four patients underwent PE as primary treatment and 32 patients for recurrent disease after pelvic radiotherapy. Median age was 57 years (range, 35-81 years). Bricker (n = 17), Mainz pouch (n = 10), and augmentation after bladder resection (n = 6) were used as urinary derivations. J-pouch coloanal anastomosis was performed in 14, colostomy in 13, and side-to-end anastomosis in 4 patients. There was no operative mortality. The most important postoperative complications were rectovaginal fistula (5), urinary leakage (2), vesicovaginal fistula (1), and sepsis (3). One of the 6 patients with a partial cystectomy developed a vesicovaginal fistula, which was successfully treated with a Martius flap. With a median follow-up of 78 months (range, 2-131) months, the 5-year overall and disease-specific survival (DSS) rates were 44% and 52%, respectively. Five-year DSS for cervical, endometrial, and vaginal/vulvar cancer was 44%, 80%, and 57%, respectively. Combined operative and radiotherapeutic treatment (CORT) was performed in 3 patients with pelvic side wall relapse. Of the 15 patients 65 years or older, a 5-year DSS of 71% was observed in comparison with 42% in the younger subgroup, and their complication rates were similar to the younger patient group. Thirteen patients (36%) reported to have psychological disturbances associated with stoma-related problems. Only 3 patients requested a vaginal reconstruction during follow-up. CONCLUSIONS: Pelvic exenteration offers a sustained survival with an acceptable morbidity in patients with advanced or recurrent gynecologic cancer. Older age was not associated with higher morbidity/mortality in this series.

Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome.

BACKGROUND: The interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer has arbitrarily been set at 6-8 weeks. However, tumor regression is variable. This study aimed to evaluate whether the interval between neoadjuvant therapy and surgery had an impact on pathologic response and on surgical and oncologic outcome. METHODS: A total of 356 consecutive patients with clinical stage II and III rectal adenocarcinoma were identified. Median age was 63 years, and 65 % were men. All patients received neoadjuvant chemoradiotherapy (45 Gy) with a continuous infusion of 5-fluorouracil. Data on neoadjuvant-surgery interval, type of surgery, pathology, postoperative complications, length of hospital stay, disease recurrence, and survival were reviewed. Patients were divided into two groups according to the interval between neoadjuvant therapy and surgery: ≤ 7 weeks (short interval, n = 201) and >7 weeks (long interval, n = 155). RESULTS: The complete pathologic response rate was 21 %. It was significantly higher after a longer interval (28 %) than after a shorter interval (16 %, p = 0.006). A longer interval did not affect morbidity or length of hospital stay. After a median follow-up of 4.9 years, the 5-year cancer-specific survival rate was 83 % in the short-interval group versus 91 % in the long-interval group (p = 0.046), and the free-from-recurrence rate was 73 versus 83 %, respectively (p = 0.026). CONCLUSIONS: In this retrospective analysis, there seems to be an association between a longer interval after neoadjuvant chemoradiotherapy and complete pathologic response without affecting postoperative morbidity and length of hospital stay, and with no detrimental effect on oncologic outcome.

Value of diffusion-weighted magnetic resonance imaging for prediction and early assessment of response to neoadjuvant radiochemotherapy in rectal cancer: preliminary results.

PURPOSE: To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). METHODS AND MATERIALS: Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10-15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0-1000 s/mm(2)) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change (∆ADC), and volume change (∆V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectal excision (pathologic complete response [pCR] vs. no pCR, ypT0-2 vs. ypT3-4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, ∆ADC, and ∆V for the detection of pCR was compared with receiver operating characteristics analysis. RESULTS: Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm(2)/s: 0.94 ± 0.12 × 10(-3) vs. 1.19 ± 0.22 × 10(-3), p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: ΔV(during): -62 ± 16 vs. -33 ± 16, respectively, p = 0.015; and ΔV(post): -86 ± 12 vs. -60 ± 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the ΔV(during) and, respectively, 83% and 86% for the ΔV(post). The ∆ADC during (ΔADC(during)) and after RCT (ΔADC(post)) showed a significantly higher value in patients with pCR compared with patients without (in %: ΔADC(during): 72 ± 14 vs. 16 ± 12, p = 0.0006; and ΔADC(post): 88 ± 35 vs. 26 ± 19, p = 0.0011), yielding a sensitivity and specificity of 100% for the ΔADC(during) and, respectively, 100% and 93% for the ΔADC(post). CONCLUSIONS: These initial findings indicate that DWI, using pretreatment ADC, ΔADC(during), and ΔADC(post) may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements.

Treatment of small-bowel fistulae in the open abdomen with topical negative-pressure therapy.

BACKGROUND: An open abdomen (OA) can result from surgical management of trauma, severe peritonitis, abdominal compartment syndrome, and other abdominal emergencies. Enteroatmospheric fistulae (EAF) occur in 25% of patients with an OA and are associated with high mortality. METHODS: We report our experience with topical negative pressure (TNP) therapy in the management of EAF in an OA using the VAC (vacuum asisted closure) device (KCI Medical, San Antonio, TX). Nine patients with 17 EAF in an OA were treated with topical TNP therapy from January 2006 to January 2009. Surgery with enterectomy and abdominal closure was planned 6 to 10 weeks later. RESULTS: Three EAF closed spontaneously. The median time from the onset of fistulization to elective surgical management was 51 days. No additional fistulae occurred during VAC therapy. One patient with a short bowel died as a result of persistent leakage after surgery. CONCLUSIONS: Although previously considered a contraindication to TNP therapy, EAF can be managed successfully with TNP therapy. Surgical closure of EAFs is possible after several weeks.

Surgical treatment of deeply infiltrating endometriosis with colorectal involvement.

BACKGROUND: Treatment of colorectal endometriosis is difficult and challenging. We reviewed the clinical outcome of surgical treatment of deeply infiltrating endometriosis (DIE) with colorectal involvement. METHODS: Review was based upon a literature search using following search terms: (1) 'surgery' and 'colorectal endometriosis', (2) 'bowel' and 'endometriosis' and 'surgery'. INCLUSION CRITERIA: clear explanation of surgical technique and follow-up data on at least one of the following items: complications, pain, quality of life (QOL), fertility and recurrence. RESULTS: Most of the 49 studies included complications (94%) and pain (67%); few studies reported recurrence (41%), fertility (37%) and QOL (10%); only 29% reported (loss of) follow-up. Out of 3894 patients, 71% received bowel resection anastomosis, 10% received full-thickness disc excision and 17% were treated with superficial surgery. Comparison of clinical outcome between different surgical techniques was not possible. Post-operative complications were present in 0-3% of the patients. Although pain improvement was reported in most studies, pain evaluation was patient-based in <50% (Visual Analogue Scale in only 18%). While QOL was improved in most studies, prospective data were only available for 149 patients. Pregnancy rates were 23-57% with a cumulative pregnancy rate of 58-70% within 4 years. The overall endometriosis recurrence rate in studies (>2 years follow-up) was 5-25% with most of the studies reporting 10%. Owing to highly variable study design and data collection, a CONSORT-inspired checklist was developed for future studies. CONCLUSIONS: Prospective studies reporting standardized and well-defined clinical outcome after surgical treatment of DIE with colorectal involvement with long-term follow-up are needed.