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.

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).

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.

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.

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).

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.

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.

Outcome standards for an organ preservation strategy in stage II and III rectal adenocarcinoma after neoadjuvant chemoradiation.

BACKGROUND: Neoadjuvant chemoradiotherapy is the standard of care for patients with locally advanced mid and distal rectal cancer. Tumor regression is variable, and this study was designed to evaluate the pathological response and impact on long-term disease control in responders and nonresponders. METHODS: A total of 303 consecutive patients with cStage II and III mid and distal rectal adenocarcinoma were identified. The mean age was 64 years and 63% were men. Patients received neoadjuvant chemoradiotherapy (45 Gy) with a continuous infusion of 5-fluorouracil. Total mesorectal excision (TME) was performed after an interval of 6-8 weeks. Tumors were stratified as responders (ypT0 or ypT1) and nonresponders (≥ypT3). All ypT2 were separately categorized. RESULTS: Tumors of 84 patients were classified as responders (27.5%) versus nonresponders in 144 patients (47.5%). Pathological tumor stage was ypT2 in 75 patients (25%). After a median follow-up of 55 months, the 5-year cancer-specific survival rate was 98% and the disease-free survival rate was 91% in responders versus 82% (P < 0.0025) and 60% (P < 0.0001), respectively, for the nonresponders. CONCLUSIONS: After neoadjuvant chemoradiotherapy and TME surgery for locally advanced rectal cancer and complete or near-complete pathological tumor response oncological outcome is very good. These results set the standards for a rectum-sparing strategy.

Laparoscopic sigmoid resection with transrectal specimen extraction has a good short-term outcome.

BACKGROUND: Transrectal specimen extraction in laparoscopic sigmoid resection avoids a muscle-split incision for specimen retrieval. A technique for transrectal specimen extraction is described, and the results of a pilot study concerning feasibility are presented. METHODS: All consecutive patients undergoing laparoscopic sigmoid resection with transrectal specimen extraction were included in this observational study. A specimen retrieval pouch was used to facilitate specimen extraction. All preoperative and operative data, postoperative morbidity, and short-term outcome were gathered in a database. RESULTS: The described technique was used to treat 21 patients. The median age of the patients was 41 years (interquartile range [IQR], 34-66 years). The median body mass index (BMI) was 23 kg/m2 (IQR, 22-26 kg/m2), and 90% of the patients were women. Of the 21 patients, 13 (62%) underwent a resection for endometriosis, 5 (24%) had resection for diverticular disease, and 3 (14%) underwent a tumor resection. The median operating time was 105 min (IQR, 90-110 min), and the median intraoperative blood loss was 10 ml (IQR, 0-20 ml). All the procedures except one (95%) were performed within 2 h. The median length of the extracted specimen was 20 cm (IQR, 13-25 cm). There was one anastomotic leak (5%), treated by emergency laparotomy and creation of a new colorectal anastomosis. None of the patients required a temporary diverting stoma, and no postoperative mortality occurred. The median hospital stay was 6 days (IQR, 5-7 days). All the patients did well during a median follow-up period of 3.6 months, and none reported any anal dysfunction. CONCLUSIONS: Laparoscopic sigmoid resection with transrectal specimen extraction is feasible and has a good short-term outcome.

Laparoscopic inguinal hernia repair in men with lightweight meshes may significantly impair sperm motility: a randomized controlled trial.

OBJECTIVE: To compare quality of life and fertility aspects after laparoscopic inguinal hernia repair in men using a heavyweight or lightweight mesh. SUMMARY BACKGROUND DATA: The use of lightweight meshes in laparoscopic inguinal hernia repair could have beneficial effects on quality of life and preservation of the spermatic structures due to a decreased foreign-body reaction. METHODS: A total of 59 male patients planned for primary, unilateral or bilateral inguinal hernia repair were randomized between a standard polypropylene (Marlex) or lightweight mesh (Vypro II, TiMesh). Main outcome measures were fertility aspects, assessed preoperatively and at 1-year follow-up by semen analysis and scrotal ultrasonography. Secondary outcomes were quality of life (SF-36 and McGill Pain Questionnaire) and recurrence up to 1 year postoperatively. RESULTS: Patients operated on with a VyproII or TiMesh mesh exhibited a decreased sperm motility (vs. preoperatively) compared with Marlex patients, respectively -9.5% and -5.5% versus +2% (P = 0.013). When the results after uni- and bilateral hernia repair were analyzed separately, this difference only remained significant in the bilateral hernia subgroup: -10% for VyproII and -17% for TiMesh versus +1% for Marlex (P = 0.037). Other fertility parameters (sperm concentration, morphology, and alpha-glucosidase level) were unchanged. There were no differences at any study point between the 3 groups regarding quality of life. Only for resumption of sport activities was a small advantage noted for VyproII versus Marlex patients (P = 0.045). After 1 year, no recurrences were observed; 3 patients (6%) complained of chronic disabling pain. CONCLUSIONS: Our data suggest that the use of lightweight meshes for laparoscopic inguinal hernia repair in male patients negatively influences sperm motility, without any benefit on quality of life. These alterations might be important in a subgroup of young male patients operated on laparoscopically for a bilateral hernia. This study was registered in the clinicaltrials.gov database (ID number NCT00925067).

Factors predicting the quality of total mesorectal excision for rectal cancer.

OBJECTIVE: To determine preoperative tumor-, patient-, and treatment-related factors that are independently associated with incomplete mesorectal excision. SUMMARY OF BACKGROUND DATA: Incomplete total mesorectal excision (TME) for rectal cancer is associated with increased local and overall recurrences. Factors predicting incomplete mesorectal excision have scarcely been studied. METHODS: In the context of PROCARE, a Belgian multidisciplinary project on rectal cancer, the quality of 266 consecutive and anonymized TME specimens submitted by 33 candidate-TME-trainers was graded by a blinded pathology review board in a standardized manner. Uni- and multivariable analysis were performed to identify factors that can independently predict incomplete mesorectal excision. RESULTS: Mesorectal resection was complete in 21%, nearly complete in 47%, and incomplete in 32%. Of 57% of TME specimens the grade of resection had not been reported by the local pathologist. Incomplete TME doubled the incidence of a positive circumferential resection margin (P = 0.004). Factors found to be significantly related to incomplete TME in univariate analysis were as follows: surgeon, female gender, pathologic body mass index, low rectal cancer, negative clinical nodal status, the absence of downstaging after long-course chemoradiation, laparoscopic and converted laparoscopic resection, and abdominoperineal resection. Multivariable analysis identified pathologic body mass index (P = 0.017), the absence of downstaging after long-course chemoradiation (P = 0.0005), and laparoscopic or converted laparoscopic resection (P = 0.014) as factors that are independently associated with incomplete mesorectal excision. CONCLUSION: Good TME quality cannot be guaranteed. This peer-reviewed TME assessment revealed a number of factors that are independently related to incomplete TME. Both specimen and pathology report need to be audited.

The use of FDG-PET/CT and diffusion-weighted magnetic resonance imaging for response prediction before, during and after preoperative chemoradiotherapy for rectal cancer.

PURPOSE: To investigate the use of FDG-PET/CT before, during and after chemoradiotherapy (CRT) and diffusion-weighted magnetic resonance imaging (DW-MRI) before CRT for the prediction of pathological response (pCR) in rectal cancer patients. MATERIAL AND METHODS: Twenty-two rectal cancer patients treated with long course CRT were included. An FDG-PET/CT was performed prior to the start of CRT, after 10 to 12 fractions of CRT and five weeks after the end of CRT. The tumor was delineated using a gradient based delineation method and the maximal standardized uptake values (SUV(max)) were calculated. A DW-MRI was performed before start of CRT. Mean apparent diffusion coefficients (ADC) were determined. The ΔSUV(max) during and after CRT and the initial ADC values were correlated to the histopathological findings after total mesorectal excision (TME). RESULTS: ΔSUV(max) during and after CRT significantly correlated with the pathological response to treatment (during CRT: ΔSUV(max) = 59% ± 12% for pCR vs. 25% ± 27% if no pCR, p=0.0036; post-CRT: 90% ± 11 for pCR vs. 63% ± 22 if no pCR p=0.013). ROC curve analysis revealed an optimal threshold for ΔSUV(max) of 40% during CRT and 76% after CRT. The initial ADC value was also significantly correlated with pCR (0.94 ± 0.12 × 10(-3) mm(2)/s for pCR vs. 1.2 ± 0.24 × 10(-3) mm(2)/s, p=0.002) and ROC curve analysis revealed an optimal threshold of 1.06 × 10(-3) mm(2)/s. Combining the provided ΔSUV(max) thresholds during and after CRT increased specificity of the prediction (sensitivity 100% and specificity 94%). The combination of the thresholds for the initial ADC value and the ΔSUV(max) during CRT increased specificity of the prediction to a similar level (sensitivity of 100% and specificity of 94%). CONCLUSIONS: The combination of the different time points and the different imaging modalities increased the specificity of the response assessment both during and after CRT.

Outcome after proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: During the course of their disease, about 30% of patients with ulcerative colitis (UC) will undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA). We evaluated the outcome of IPAA in a Belgian referral center. METHODS: Clinical charts were reviewed for pre- and postoperative disease course, functional outcome, and complications in all patients with UC (n = 182) and indeterminate colitis (n = 2) who underwent IPAA in 1990-2004. RESULTS: Follow-up data were available in 173 out of 184 patients (67 female, median age at proctocolectomy 39.0 years). Median functional Oresland score 1 year after IPAA was 3 (range 0-11). Early postoperative complications were seen in 27% of patients. After a median (interquartile range) follow-up of 6.5 (3.4-9.9) years, 35% of patients developed septic and/or obstructive complications. Forty-six percent of patients developed at least 1 episode of pouchitis. Risk factors for pouchitis were the presence of extraintestinal manifestations (odds ratio [OR] 1.92 (1.23-3.01), P = 0.004) and younger age at proctocolectomy (P = 0.004). Chronic pouchitis was present in 33 patients and associated with extraintestinal manifestations (OR 2.93 (1.13-7.62), P = 0.027), backwash ileitis (OR 9.28 (1.71-50.49), P = 0.010), and length of follow-up (P = 0.004). Pouch failure occurred in 5% of patients. CONCLUSIONS: Although proctocolectomy with IPAA surgery has a good functional outcome, postoperative complications, especially pouchitis, remain considerable in patients with UC.

Quantitative RT-PCR detection of colorectal tumor cells in peripheral blood--a systematic review.

BACKGROUND: Twenty percent to 40% of patients with node-negative colorectal cancer die of metastatic disease. Detection of cancer cell dissemination has been proposed as a tool to select patients at highest risk for recurrence. In this review, we summarize the evidence for detection with quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assays of circulating tumor cells (CTCs) in peripheral blood of colorectal cancer patients. MATERIALS AND METHODS: Pubmed and Embase were systematically searched for all English publications relevant to circulating cancer cells, peripheral blood, quantitative RT-PCR (q-RT-PCR), and colorectal cancer. Cross-references and the "related articles" function were used to broaden the search. Manuscripts reporting on the results of nonquantitative RT-PCR assays were excluded. The study methodology, CTCs detection rates in peripheral blood, and prognostic value were reviewed. RESULTS: Twelve manuscripts on qRT-PCR were retrieved. Stage dependence was found for detection of CTCs in four of 10 studies. From univariate analysis performed for disease-free survival and overall survival in 4 of 12 studies, there was evidence (P < 0.05) for an effect of the detection of CTCs with qRT-PCR. None of the included trials identified detection of CTCs in peripheral blood as an independent predictor of survival. CONCLUSION: Quantification of CTCs in peripheral blood holds promise in predicting stage and outcome in colorectal cancer patients. At present, evidence from the literature is too scarce to integrate quantitative RT-PCR assays to detect CTCs into the management of colorectal cancer.

Biological image-guided radiotherapy in rectal cancer: is there a role for FMISO or FLT, next to FDG?

PURPOSE: The purpose of this study is to investigate the use of PET/CT with fluorodeoxyglucose (FDG), fluorothymidine (FLT) and fluoromisonidazole (FMISO) for radiotherapy (RT) target definition and evolution in rectal cancer. MATERIALS AND METHODS: PET/CT was performed before and during preoperative chemoradiotherapy (CRT) in 15 patients with resectable rectal cancer. PET signals were delineated and CT images on the different time points were non-rigidly registered. Mismatch analyses were carried out to quantify the overlap between FDG and FLT or FMISO tumour volumes (TV) and between PET TVs over time. RESULTS: Ninety sequential PET/CT images were analyzed. The mean FDG, FLT and FMISO-PET TVs showed a tendency to shrink during preoperative CRT. On each time point, the mean FDG-PET TV was significantly larger than the FMISO-PET TV but not significantly larger than the mean FLT-PET TV. There was a mean 65% mismatch between the FMISO and FDG TVs obtained before and during CRT. FLT TVs corresponded better with the FDG TVs (25% mismatch before and 56% during CRT). During CRT, on average 61% of the mean FDG TV (7 cc) overlapped with the baseline mean TV (15.5 cc) (n=15). For FLT, the TV overlap was 49% (n=5) and for FMISO only 20% of the TV during CRT remained inside the contour at baseline (n=10). CONCLUSION: FDG, FLT and FMISO-PET reflect different functional characteristics that change during CRT in rectal cancer. FLT and FDG show good spatial correspondence, while FMISO seems less reliable due to the non-specific FMISO uptake in normoxic tissue and tracer diffusion through the bowel wall. FDG and FLT-PET/CT imaging seem most appropriate to integrate in preoperative RT for rectal cancer.

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.

Definition and delineation of the clinical target volume for rectal cancer.

PURPOSE: Optimization of radiation techniques to maximize local tumor control and to minimize small bowel toxicity in locally advanced rectal cancer requires proper definition and delineation guidelines for the clinical target volume (CTV). The purpose of this investigation was to analyze reported data on the predominant locations and frequency of local recurrences and lymph node involvement in rectal cancer, to propose a definition of the CTV for rectal cancer and guidelines for its delineation. METHODS AND MATERIALS: Seven reports were analyzed to assess the incidence and predominant location of local recurrences in rectal cancer. The distribution of lymphatic spread was analyzed in another 10 reports to record the relative frequency and location of metastatic lymph nodes in rectal cancer, according to the stage and level of the primary tumor. RESULTS: The mesorectal, posterior, and inferior pelvic subsites are most at risk for local recurrences, whereas lymphatic tumor spread occurs mainly in three directions: upward into the inferior mesenteric nodes; lateral into the internal iliac lymph nodes; and, in a few cases, downward into the external iliac and inguinal lymph nodes. The risk for recurrence or lymph node involvement is related to the stage and the level of the primary lesion. CONCLUSION: Based on a review of articles reporting on the incidence and predominant location of local recurrences and the distribution of lymphatic spread in rectal cancer, we defined guidelines for CTV delineation including the pelvic subsites and lymph node groups at risk for microscopic involvement. We propose to include the primary tumor, the mesorectal subsite, and the posterior pelvic subsite in the CTV in all patients. Moreover, the lateral lymph nodes are at high risk for microscopic involvement and should also be added in the CTV.